Clinica e terapia (aprile 2003 - aprile 2012)


Legionella pneumonia presenting with bilateral flank pain, hyponatraemia and acute renal failure

Birkin C, Biyani CS, Browning AJ.

Department of Urology, Pinderfields General Hospital, Wakefield, UK.

Can Urol Assoc J. 2011 Dec;5(6):E96-E100.

ABSTRACT: Legionnaires' disease (LD) is an often overlooked but a possible cause of sporadic community acquired pneumonia. High fever, cough and gastrointestinal symptoms are non-specific symptoms. Hyponatremia is more common in LD than pneumonia linked with other causes. A definitive diagnosis is usually confirmed by culture, urinary antigen testing for Legionella species. Macolide or quinolone antibiotic is the treatment of choice. We describe a case of Legionella pneumonia presenting with high fever, bilateral flank pain and oliguria. It is important for clinicians to be aware of this diagnosis when managing patients with flank pain. The case highlights the problems in differentiating LD from renal colic and the importance of proper history, physical examination with laboratory tests for appropriate management.


Legionella pneumophila lung abscess associated with immune suppression

Guy SD, Worth LJ, Thursky KA, Francis PA, Slavin MA.

Department of Infectious Diseases, Western Health, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Intern Med J. 2011 Oct;41(10):715-21.

ABSTRACT: Legionella species are a common cause of community-acquired pneumonia, infrequently complicated by cavitary disease. We describe Legionella pneumophila pneumonia and abscess formation in an immunosuppressed patient receiving corticosteroid therapy for metastatic breast carcinoma. The predisposing role of corticosteroids is discussed and the management of this complication is reviewed.


Native valve endocarditis due to a novel strain of Legionella

Pearce MM, Theodoropoulos N, Noskin GA, Flaherty JP, Stemper ME, Aspeslet T, Cianciotto NP, Reed KD.

Department of Microbiology and Immunology, Northwestern University, Chicago, Illinois, USA.

J Clin Microbiol. 2011 Sep;49(9):3340-2.

ABSTRACT: Legionellae are Gram-negative bacteria which are capable of causing disease, most commonly in the form of pneumonia. We describe a case of native valve endocarditis caused by a Legionella strain which by genotypic (16S rRNA and mip gene sequencing) and phenotypic analyses is unlike previously described strains of Legionella.


A case of severe thrombotic thrombocytopenic purpura with concomitant legionella pneumonia: review of pathogenesis and treatment

Talebi T, Fernandez-Castro G, Montero AJ, Stefanovic A, Lian E.

University of Miami Sylvester Comprehensive Cancer Center, Miami, FL.

Am J Ther. 2011 Sep;18(5):e180-5.

ABSTRACT: Thrombotic thrombocytopenia purpura (TTP) is a severe multisystem disorder characterized by fever, microangiopathic hemolytic anemia, thrombocytopenia, neurologic symptoms, and impaired renal function. Platelet counts are usually diminished, whereas the bone marrow shows a large number of megakaryocytes indicating peripheral destruction and consumption of platelets. Coagulation studies in patients with TTP are normal or slightly elevated, which helps differentiate this entity from disseminated intravascular coagulation. The peripheral smear shows an abundance of schistocytes, reticulocytes, and, at times, nucleated red blood cells. Serum lactate dehydrogenase and indirect bilirubin are elevated as a result of mechanical destruction of red blood cells. Legionella pneumophila has been identified as a relatively common cause of both community-acquired and hospital-acquired pneumonia. An association between Legionella and TTP has only been cited once in the literature. Here we present a case of severe TTP with concurrent Legionella infection. Our patient presented with the classic clinical findings of TTP and an ADAMTS13 level of less than 5% associated with an inhibitor. After a 3-week treatment course with plasma exchange, steroids, and antibiotics, he had complete clinical recovery and his ADAMTS13 level increased to greater than 75%.


Legionella micdadei, a new cause of prosthetic joint infection

Fernández-Cruz A, Marín M, Castelo L, Usubillaga R, Martín-Rabadán P, Bouza E; GAIO (Group for the Assessment of Osteoarticular Infections) Study Group.

Servicio de Microbiología Clínica y Enfermedades Infecciosas, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain.

J Clin Microbiol. 2011 Sep;49(9):3409-10.

ABSTRACT: Extrapulmonary infections caused by Legionella spp. other than Legionella pneumophila are rare. We report what is, to our knowledge, the first description of a prosthetic joint infection due to Legionella spp. Systematic testing of samples with suspected prosthetic infection by molecular biology techniques was essential. Legionella micdadei should be added to the list of microorganisms causing prosthetic joint infection.


Legionella jordanis in hematopoietic SCT patients radiographically mimicking invasive mold infection

Meyer R, Rappo U, Glickman M, Seo SK, Sepkowitz K, Eagan J, Small TN.

Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

Bone Marrow Transplant. 2011 Aug;46(8):1099-103.

ABSTRACT: Opportunistic pulmonary infections are a major cause of post-transplant morbidity and mortality. Among these infections, Aspergillus is a common cause of fatal pneumonia. Owing to the precarious clinical condition of many patients who acquire invasive mold infections, clinicians often treat them on the basis of radiographic findings, such as the halo sign. However, in patients who do not respond to treatment or who have uncommon presentations, bronchoscopy or lung biopsy looking for other pathogens should be considered. This study describes two cases in which the radiographic halo signs characteristic of Aspergillus were in fact due to Legionella jordanis, a pathogen that has been culture proven only in two patients previously (both of whom had underlying lung pathology) and diagnosed by serologic evidence in several other patients. In immunocompromised patients, Legionella can present as a cavitary lesion. Thus, presumptive treatment for this organism should be considered in post-transplant patients who do not have a classic presentation for invasive fungal infection and/or who fail to respond to conventional treatment. These cases illustrate the importance of obtaining tissue cultures to differentiate among the wide variety of pathogens present in this patient population.


First case of Legionella pneumophila native valve endocarditis

Samuel V, Bajwa AA, Cury JD.

University of Florida, Health Science Center Jacksonville, 655 West 8th Street, Jacksonville, FL 32209, USA.

Int J Infect Dis. 2011 Aug;15(8):e576-7.

ABSTRACT: We report the first case in the English language literature, to our knowledge, of native valve endocarditis due to Legionella pneumophila. The patient had no prior history of cardiothoracic intervention or congenital valvular process. A transesophageal echocardiogram showed a vegetation on the aortic valve. Blood culture and bronchoalveolar lavage returned positive for L. pneumophila. The patient was treated with levofloxacin for 6 weeks total after a second set of blood cultures were negative. The patient survived a complicated hospital course and was discharged to a rehabilitation facility.


Organizing pneumonia pattern in the follow-up CT of Legionella-infected patients

Haroon A, Higa F, Hibiya K, Haranaga S, Yara S, Tateyama M, Fujita J.

Department of Infectious, Respiratory, and Digestive Medicine, Control and Prevention of Infectious Diseases (First Department of Internal Medicine), Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0125, Japan.

J Infect Chemother. 2011 Aug;17(4):493-8.

ABSTRACT: The main aim of this study was to describe the appearance of the CT pattern of organizing pneumonia in Legionella-infected patients. Serial CT scans obtained from five sporadic cases of Legionella pneumophila pneumonia were retrospectively reviewed. The mean time of follow-up was 14 days. Chest CT was analyzed with regard to frequency and appearance of CT patterns of pulmonary abnormalities. Consolidation and ground-glass opacities, with or without an air bronchogram, were the most common abnormalities detected in CT scans during follow-up patients with L. pneumophila pneumonia. Two patterns were observed: subpleural and peribronchovascular. The subpleural pattern was seen in four patients and the peribronchovascular pattern in one. Interlobular septal thickening was seen in one patient. Pleural effusion was seen in one patient. The CT pattern of organizing pneumonia, a subpleural pattern, was frequently observed after treatment of L. pneumophila pneumonia.


Post-infection immunocomplex glomerulonephritis and Legionnaires' disease in a patient with adult Still's disease during treatment with interleukin 1 receptor antagonist anakinra: a case report

Scholtze D, Varga Z, Imhof A.

Department of Internal Medicine, University Hospital Zürich, Raemistrasse 100, CH-8091 Zürich, Switzerland.

J Med Case Reports. 2011 Jul 9;5:299.

ABSTRACT: INTRODUCTION: Legionellosis is a systemic disease that primarily affects the lungs. However, dysfunction in many organ systems, including the kidneys, has also been described. There are only a few reported cases of renal dysfunction in patients with legionellosis.

CASE PRESENTATION: A 27-year-old Caucasian woman with known adult Still's disease was admitted to our hospital for community-acquired pneumonia, due to Legionella infection, with acute renal failure. Although her respiratory symptoms responded well to antibiotic treatment, her renal function worsened, with severe proteinuria and edema. A renal biopsy showed extracapillary and endocapillary proliferative glomerulonephritis with accompanying chronic and acute interstitial nephritis. This was consistent with a post-infection immunocomplex glomerulonephritis. After initiation of steroid therapy, her renal function improved. Additionally, therapy with diuretics and an angiotensin-converting enzyme inhibitor was initiated because of persistent proteinuria. Under this treatment regimen, her severe edema and proteinuria disappeared.

CONCLUSION: To the best of our knowledge, there is only a handful of reported cases of post-infection glomerulonephritis with a nephrotic syndrome in a patient with legionellosis. Our findings suggest that, in patients with Legionnaires' disease with renal failure, post-infection immunocomplex glomerulonephritis should be considered and steroid therapy may be an effective modality to treat the renal complication.


Role of rifampin-based combination therapy for severe community-acquired Legionella pneumophila pneumonia

Varner TR, Bookstaver PB, Rudisill CN, Albrecht H.

Pediatrics, Department of Pharmacy, Palmetto Health Richland, Columbia, SC, USA.

Ann Pharmacother. 2011 Jul;45(7-8):967-76.

ABSTRACT: OBJECTIVE: To review the literature concerning the role of rifampin in the combination treatment of Legionella pneumophila pneumonia.

DATA SOURCES: A search of MEDLINE and Ovid databases was conducted (January 1970-May 2011) using the search terms Legionella pneumophila, pneumonia, Legionnaires' disease, rifampin or rifampicin, macrolide, fluoroquinolone, erythromycin, clarithromycin, levofloxacin, ciprofloxacin, and moxifloxacin

STUDY SELECTION AND DATA EXTRACTION: In vivo studies published in English that compared antimicrobial therapies including rifampin for the treatment of Legionella pneumonia, as well as in vitro studies including an assessment of rifampin bioactivity, were included.

DATA SYNTHESIS: Macrolides and fluoroquinolones have been effective as monotherapy in the treatment of L. pneumophila pneumonia. This review includes evidence summaries from 4 bioactivity evaluations, 6 clinical studies, and 6 reported cases of combination rifampin use. Combined with supporting evidence, the role of combination rifampin therapy is further delineated.

CONCLUSIONS: Interpretation of the data is limited by the potential for selection bias and lack of consistent comparators. Rifampin therapy should be considered only for patients with severe disease or significant comorbid conditions (eg, uncontrolled diabetes, smoking, or obstructive lung disease) including immunocompromised hosts and those refractory to conventional monotherapy regimens. Caution for significant adverse drug events and drug-drug interactions should be taken with the addition of rifampin.


Activity of finafloxacin, a novel fluoroquinolone with increased activity at acid pH, towards extracellular and intracellular Staphylococcus aureus, Listeria monocytogenes and Legionella pneumophila

Lemaire S, Van Bambeke F, Tulkens PM.

Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute, Université catholique de Louvain, UCL 73.70, Avenue E. Mounier 73, B-1200 Brussels, Belgium.

Int J Antimicrob Agents. 2011 Jul;38(1):52-9.

ABSTRACT: Finafloxacin, an 8-cyano-substituted fluoroquinolone, expresses enhanced activity at acidic pH and is less susceptible to several fluoroquinolone resistance determinants. In this study, we compared finafloxacin and ciprofloxacin for (i) activity against ciprofloxacin-susceptible and -resistant Staphylococcus aureus as well as wild-type and Lde efflux-positive (Lde+) Listeria monocytogenes, (ii) accumulation in THP-1 macrophages and (iii) intracellular activity towards phagocytised S. aureus, L. monocytogenes and Legionella pneumophila (developing in acidic, neutral and mildly acidic environments, respectively), using a pharmacological approach assessing drug potencies and maximal relative efficacies (E(max)). Finafloxacin minimum inhibitory concentrations (MICs) were two-fold lower than those of ciprofloxacin against meticillin-susceptible S. aureus ATCC 25923, were only modestly increased in an isogenic strain overexpressing NorA and were ≤0.25 mg/L for community-acquired meticillin-resistant S. aureus. No loss of activity was seen in Lde+ L. monocytogenes. An acidic pH decreased the MIC of finafloxacin and increased that of ciprofloxacin both for S. aureus and L. monocytogenes, in parallel with corresponding changes in drug accumulation (tested with S. aureus ATCC 25923 only). Finafloxacin accumulated less than ciprofloxacin in THP-1 cells, but the situation was reversed by exposure of cells to acid pH. In S. aureus-infected cells, acid pH increased the potency of finafloxacin without change of E(max), whilst decreasing the potency and the maximal relative efficacy of ciprofloxacin (less negative E(max)). Finafloxacin was more potent and showed larger E(max) than ciprofloxacin against phagocytised L. pneumophila, but was less potent against phagocytised L. monocytogenes. Finafloxacin appears to be an acid-pH-favoured antibiotic that may find useful applications in infections where the local pH is low.


In vitro intracellular activity and in vivo efficacy of modithromycin, a novel bicyclolide, against Legionella pneumophila

Sato T, Tateda K, Kimura S, Ishii Y, Yamaguchi K.

Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Ota-ku, Tokyo 143-8540, Japan.

Antimicrob Agents Chemother. 2011 Apr;55(4):1594-7.

ABSTRACT: The in vitro and in vivo activities of modithromycin, a novel bicyclolide, against Legionella pneumophila were compared with those of telithromycin, clarithromycin, azithromycin, and levofloxacin. All the test agents decreased the intracellular growth of viable L. pneumophila bacteria over 96 h of incubation in both types of cells used, A/J mouse-derived macrophages and A549 human alveolar epithelial cells, at extracellular concentrations of 4× and 16× MIC, respectively. However, when the agents were removed from the medium after exposure for 2 h, regrowth of intracellular bacteria occurred in both cell systems when they were exposed to telithromycin, clarithromycin, and levofloxacin but not when they were exposed to modithromycin and azithromycin. Once-daily administration of modithromycin at a dose of 10 mg/kg of body weight for 5 days led to a significant decrease of intrapulmonary viable L. pneumophila bacteria in immunosuppressed A/J mice. The efficacy of modithromycin was superior to the efficacies of telithromycin and clarithromycin and comparable to the efficacies of azithromycin and levofloxacin. In addition, modithromycin and azithromycin inhibited the intrapulmonary regrowth of bacteria even at 72 h after the last treatment, but telithromycin and levofloxacin did not. These results suggested that modithromycin has longer-lasting cellular pharmacokinetic features like azithromycin. In conclusion, modithromycin, as well as azithromycin, has excellent in vitro and in vivo bactericidal activities and persistent efficacy against intracellular L. pneumophila. Modithromycin should be a useful agent for treatment of pulmonary infections caused by this pathogen. 


Activities of tigecycline and comparators against Legionella pneumophila and Legionella micdadei extracellularly and in human monocyte-derived macrophages

Bopp LH, Baltch AL, Ritz WJ, Michelsen PB, Smith RP.

Stratton VA Medical Center, Albany, NY, USA.

Diagn Microbiol Infect Dis. 2011 Jan;69(1):86-93.

ABSTRACT: The activity of tigecycline against Legionellae, which are intracellular pathogens, was evaluated intracellularly in human phagocytes and extracellularly, and compared to the activities of erythromycin and levofloxacin. Clinical isolates of L. pneumophila serogroups 1, 5, and 6 and L. micdadei were tested in time-kill experiments. Extracellular experiments were done using buffered yeast extract broth. For intracellular assays, monolayers of human monocyte-derived macrophages (MDM) were infected with L. pneumophila or L. micdadei. Antibiotics (0.05-2.5 × MIC) were then added. MDM were lysed at 0, 24, 48, and 72 h and viable bacteria in the lysates were enumerated. Based on multiples of the MICs, tigecycline was less active extracellularly than levofloxacin or erythromycin. However, intracellular killing of both L. pneumophila and L. micdadei by tigecycline at 72 h was greater than for erythromycin or levofloxacin. Currently, evidence does not support the use of tigecycline as a first-line drug for treatment of Legionella infections. However, since Legionellae are intracellular pathogens, these results suggest that tigecycline should be effective for treatment of infections caused by these bacteria.


Identification of Legionella feeleii Cellulitis

Loridant S, Lagier JC, La Scola B.

Universite de la Mediterranee, Marseille, France (S. Loridant, J.-C. Lagier, B. LaScola); and Hopital Nord, Marseille (J.-C. Lagier).

Emerg Infect Dis. 2011 Jan;17(1):145-6.

ABSTRACT: To the Editor: In general, reports of extrapulmonary Legionella spp. infections are scarce. For example, L. micdadei infection was found with the following manifestations: a mass on the left side of the neck and low-grade fever in a healthy 9-year-old girl (1); multiple liver and lung abscesses in a 7-year-old girl with acute lymphoblastic leukemia who had undergone allogeneic cord blood transplantation (2); and a cerebral abscess in a patient with legionellosis (3).


A severe complication of anti-TNF alfa treatment

Fabroni C, Gori A, Prignano F, Lotti T.

University Unit of Dermatology and Physiotherapy, University of Florence, Florence, Italy.

G Ital Dermatol Venereol. 2010 Dec;145(6):775-7.

ABSTRACT: The antitumor necrosis factor (TNF-alpha) drugs are increasingly used in treating skin diseases such as psoriasis. TNF-alpha is a proinflammatory cytokine with a key role in the pathogenesis of psoriasis but also in host defence against bacterial pathogens, especially against those that multiply inside host cells. The effectiveness of anti-TNF-alpha in the treatment of psoriasis is now widely recognized and has led to their increasingly wide use. Although these drugs are considered relatively safe, their use is associated with an increased incidence of serious infections even in patients treated. Have been described above numerous cases of tuberculosis but has also observed an increased incidence of granulomatous infections by intracellular bacteria such as Legionella pneumophila required. Infections due to this biotic agent, if not diagnosed early, are potentially fatal. We report the case of a patient, heavy smoker, suffering from severe skin psoriasis who after starting treatment with infliximab developed a pneumonia caused by Legionella pneumophila. Our aim is to draw the attention of specialists on increasing risk of granulomatous infections by intracellular agents in patients being treated with anti TNF-alpha. 


Synthesis and biological evaluation of (+/-)-dinemasone C and analogues

Stewart AM, Meier K, Schulz B, Steinert M, Snider BB.

Department of Chemistry MS 015, Brandeis University, Waltham, Massachusetts 02454-9110, USA.

J Org Chem. 2010 Sep 3;75(17):6057-60.

ABSTRACT: Dinemasone C was prepared in three steps (8% overall yield) from cis-tetrahydro-4-hydroxy-6-methyl-2-pyrone by aldol reaction with 2,4-hexadienal, epoxidation followed by cyclization, and epimerization of the ring fusion. Dinemasone C, epi-dinemasone C, anhydrodinemasone BC, and nor-dinemasone B are active against bacteria, including Legionella pneumophila Corby, algae, and fungi.


Spontaneous rupture of the spleen associated with Legionella pneumonia

Casanova-Roman M, Casas J, Sanchez-Porto A, Nacle B.

Emergency and Intensive Care Unit; Clinical Laboratory Service, Microbiology Unit, Hospital of La Linea, Cadiz, Spain;

Can J Infect Dis Med Microbiol. 2010 Fall;21(3):e107-8.

ABSTRACT: Spontaneous rupture of the spleen associated with Legionella pneumonia is a rare and life-threatening complication; only three cases have been reported to date. The authors describe a case of a 47-year-old man who presented with pneumonia and abdominal pain. He underwent a splenectomy, and was successfully treated with clarithromycin and levofloxacin.


Clinical efficacy of moxifloxacin versus comparator therapies for community-acquired pneumonia caused by Legionella spp

Garau J, Fritsch A, Arvis P, Read RC.

Hospital Universitari Mutua de Terrassa, University of Barcelona, Spain.

J Chemother. 2010 Aug;22(4):264-6.

ABSTRACT: The aim of this study was to compare outcomes for patients with community-acquired pneumonia (CAP) caused by Legionella spp. following treatment with moxifloxacin or a range of comparator antimicrobial agents. Data were pooled from four sequential I.V./P.O. trials of moxifloxacin in the treatment of CAP. Comparators were ceftriaxone +/- erythromycin, amoxicillin/clavulanate +/- clarithromycin, trovafloxacin, levofloxacin, or ceftriaxone + levofloxacin. Legionella infection was diagnosed by culture, urine antigen testing and/or serology. Clinical success rates for the efficacy-valid (per protocol) populations were recorded at the test-of-cure visit (5-30 days post-therapy). Severity of CAP was determined using the modified American Thoracic Society criteria.Of 1786 efficacy-valid patients, 33 (1.8%) had documented infection with Legionella spp. (moxifloxacin: n=13; comparator: n=20). Of these, 30 cases were identified by serology and/or urine antigen detection and 3 by respiratory culture. The success rate of moxifloxacin vs. comparator therapy was 92.3% vs. 80.0% for the I.V./P.O. trials.Sequential (I.V./P.O.) moxifloxacin demonstrated clinical efficacy that was at least as good as that of comparator treatments for the treatment of CAP due to Legionella.


Activity of a novel series of acylides active against community-acquired respiratory pathogens

Pandya M, Chakrabarti A, Rathy S, Katoch R, Venkataraman R, Bhateja P, Mathur T, Kumar GR, Malhotra S, Rao M, Bhadauria T, Barman TK, Das B, Upadhyay D, Bhatnagar PK.

Department of Infectious Diseases, New Drug Discovery Research, Ranbaxy Research Laboratories, R & D III, Plot 20, Sector 18, Udyog Vihar, Gurgaon 122 001, Haryana, India.

Int J Antimicrob Agents. 2010 Aug;36(2):169-174.

ABSTRACT: Resistance to macrolides and beta-lactams has increased sharply amongst key respiratory pathogens, leading to major concern. A novel series of acylides was designed to overcome this resistance and was evaluated for in vitro and in vivo activity. This series of acylides was designed starting from clarithromycin by changing the substitution on the desosamine nitrogen, followed by conversion to 3-O-acyl and 11,12-carbamate. Minimum inhibitory concentrations (MICs) of acylides were determined against susceptible as well as macrolide-lincosamide-streptogramin B (MLS(B))- and penicillin-resistant Streptococcus pneumoniae, Streptococcus pyogenes and Moraxella catarrhalis by the agar dilution method. Microbroth MICs for Haemophilus influenzae were determined according to Clinical and Laboratory Standards Institute guidelines. In vivo efficacy was determined by target organ load reduction against S. pneumoniae 3579 (ermB). The bactericidal potential of promising acylides was also determined. MICs of these compounds against S. pneumoniae, S. pyogenes, H. influenzae and M. catarrhalis were in the range of 0.06-2, 0.125-1, 1-16 and 0.015-0.5mug/mL, respectively, irrespective of their resistance pattern. Mycoplasma pneumoniae and Legionella pneumophila showed MIC ranges of 0.004-0.125mug/mL and 0.004-0.03mug/mL, respectively. The acylides also showed better activity against telithromycin-resistant S. pneumoniae strains. Compounds with a 4-furan-2-yl-1H-imidazolyl side chain on the carbamate (RBx 10000296) showed a target organ load reduction of >3log(10) colony-forming units/mL and concentration-dependent bactericidal potential against S. pneumoniae 994 mefA and H. influenzae strains. This novel and potent series of acylides active against antibiotic-resistant respiratory pathogens should be further investigated.


Fastidious intracellular bacteria as causal agents of community-acquired pneumonia

Lamoth F, Greub G.

Infectious Diseases Service, University Hospital Center and University of Lausanne, Lausanne, Switzerland.

Expert Rev Anti Infect Ther. 2010 Jul;8(7):775-90.

ABSTRACT: Intracellular bacteria are common causes of community-acquired pneumonia that grow poorly or not at all on standard culture media and do not respond to beta-lactam antibiotic therapy. Apart from well-established agents of pneumonia such as Legionella pneumophila, Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia psittaci and Coxiella burnetii, some new emerging pathogens have recently been recognized, mainly Parachlamydia acanthamoebae and Simkania negevensis, two Chlamydia-related bacteria. Most of them are causes of benign and self-limited infections. However, they may cause severe pneumonia in some cases (i.e., Legionnaires' disease) and they may cause outbreaks representing a public health problem deserving prompt recognition and appropriate therapy. Although extrapulmonary manifestations are often present, no clinical features allow them to be distinguished from classical bacterial agents of pneumonia such as Streptococcus pneumoniae. Thus, specific molecular diagnostic tools are very helpful for early recognition of the offending bacteria, whereas serology often only allows retrospective or late diagnosis. Macrolides remain the best empirical treatment of intracellular respiratory pathogens, although some observational studies suggest that quinolones may be superior for the treatment of legionellosis.


Acute disseminating encephalomyelitis following legionnaires disease

de Lau LM, Siepman DA, Remmers MJ, Terwindt GM, Hintzen RQ.

Department of Neurology, Erasmus Medical Center, 3000 CA Rotterdam, the Netherlands.

Arch Neurol. 2010 May;67(5):623-6.

ABSTRACT: OBJECTIVE: To describe 2 patients presenting with severe neurological deficits and extensive lesions on brain magnetic resonance imaging after having experienced Legionella pneumonia. DESIGN: Case reports. SETTING: University hospital. PATIENTS: Two patients who developed severe neurological symptoms, including encephalopathic signs, following Legionella infection, with widespread lesions on magnetic resonance imaging compatible with demyelination. RESULTS: After extensive ancillary investigations, a diagnosis of acute disseminating encephalomyelitis was considered most likely. Steroid therapy was initiated in 1 of the patients, followed by plasmapheresis. In both patients, clinical and radiological signs gradually recovered, with only slight residual deficits. CONCLUSION: In patients presenting with neurological symptoms after an episode of pneumonia, Legionella infection and a subsequent immune-mediated process such as acute disseminating encephalomyelitis should be considered.


Rapid clinical diagnosis of Legionnaires' disease during the "herald wave" of the swine influenza (H1N1) pandemic: the Legionnaires' disease triad

Cunha BA, Mickail N, Syed U, Strollo S, Laguerre M.

Infectious Disease Division, Winthrop-University Hospital, Mineola, New York 11501, USA.

Heart Lung. 2010 May-Jun;39(3):249-59.

ABSRACT: BACKGROUND: In adults hospitalized with atypical community-acquired pneumonia (CAP), Legionnaires' disease is not uncommon. Legionnaire's disease can be differentiated from typical CAPs and from other atypical CAPs based on its characteristic pattern of extrapulmonary organ involvement. The first clinically useful diagnostic weighted point score system for the clinical diagnosis of Legionnaires' disease was developed by the Infectious Disease Division at Winthrop-University Hospital in the 1980s. It has proven to be diagnostically accurate and useful for more than two decades, but was time-consuming. Because Legionella spp. diagnostic tests are time-dependent and problematic, a need was perceived for a rapid, simple way to render a clinical, syndromic diagnosis of Legionnaires' disease pending Legionella test results. During the "herald wave" of the swine influenza (H1N1) pandemic in the New York area, our hospital, like others, was inundated with patients who presented to the Emergency Department with influenza-like illnesses (ILIs) for H1N1 testing/evaluation. Most patients with ILIs did not have swine influenza. Hospitalized patients with ILIs who tested positive with rapid influenza diagnostic tests (RIDTs) were placed on influenza precautions and treated with oseltamivir. Unfortunately, approximately 30% of adult patients admitted with an ILI had negative RIDTs. Because the definitive laboratory diagnosis of H1N1 pneumonia by reverse transcription-polymerase chain reaction(RT-PCR), testing was restricted by health departments, resulted in clinical and infection control dilemmas in determining which RIDT-negative patients did, in fact, have H1N1 pneumonia. OBJECTIVE: Accordingly, a diagnostic weighted point score system was developed for H1N1 pneumonia patients, based on RT-PCR positivity by the Infectious Disease Division at Winthrop-University Hospital. This diagnostic point score system for hospitalized adults with negative RIDTs was time-consuming. As the pandemic progressed, a simplified diagnostic swine influenza (H1N1) triad was developed for the rapid clinical diagnosis of probable H1N1 pneumonia, which also differentiated it from its mimics as well as from bacterial pneumonia, eg, Legionnaires' disease. During the "herald wave" of the H1N1 pandemic, we noticed an unexplained increase in Legionnaires' disease CAPs. Because clinical resources were stressed to the maximum during the pandemic, it was critically important to rapidly identify patients rapidly with Legionnaire's disease who did not require influenza precautions or oseltamivir, but who did require anti-Legionella antimicrobial therapy. METHODS: Based on the Winthrop-University Hospital Infectious Disease Division's diagnostic weighted point score system for Legionnaires' disease (modified), key indicators were identified and became the basis for the diagnostic Legionnaires' disease triad. The diagnostic Legionnaires' disease triad was used to make a clinical diagnosis of Legionnaires' disease until the results of Legionella diagnostic tests were reported. The diagnostic Legionnaires' disease triad diagnosed Legionnaires' disease in hospitalized adults with CAPs with extrapulmonary findings (atypical CAP) and relative bradycardia, accompanied by any three (ie, a triad) of the following: otherwise unexplained relative lymphopenia, early/mildly elevated serum transaminases (SGOT/SGPT), highly increased ferritin levels (> or =2 x n), or hypophosphatemia. The diagnostic Legionnaires' disease triad provides clinicians with a rapid way to clinically diagnose Legionnaires' disease, pending Legionella test results. RESULTS: The accuracy of the diagnostic Legionnaires' disease triad was confirmed in our 9 cases of Legionnaires' disease by subsequent Legionella diagnostic testing. CONCLUSIONS: The diagnostic Legionnaires' disease triad is particularly useful in situations where a rapid clinical syndromic diagnosis is needed, ie, during an H1N1 pandemic.


Clinical potential of C-reactive protein and procalcitonin serum concentrations to guide differential diagnosis and clinical management of pneumococcal and Legionella pneumonia

Bellmann-Weiler R, Ausserwinkler M, Kurz K, Theurl I, Weiss G.

Medical University of Innsbruck, Department of Internal Medicine I, Clinical Immunology and Infectious Diseases, Anichstrasse 35, A-6020 Innsbruck, Austria.

J Clin Microbiol. 2010 May;48(5):1915-7.

ABSTRACT: We retrospectively analyzed the records of 61 hospitalized patients with community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae or Legionella pneumophila. We found that serum procalcitonin and sodium concentrations were significantly lower, and ferritin levels were significantly higher, in patients infected with L. pneumophila than in those infected with S. pneumoniae. The ratio of C-reactive protein to procalcitonin significantly distinguished between the groups. High procalcitonin levels were associated with an adverse clinical course.


Macrolides versus quinolones in Legionella pneumonia: results from the Community-Acquired Pneumonia Organization international study

Griffin AT, Peyrani P, Wiemken T, Arnold F.

Department of Medicine, School of Medicine, University of Louisville, Louisville, Kentucky 40202, USA.

Int J Tuberc Lung Dis. 2010 Apr;14(4):495-9.

ABSTRACT: BACKGROUND: Data supporting a quinolone or a macrolide as preferred therapy for community-acquired pneumonia (CAP) due to Legionella pneumophila are not firmly established. Some literature suggests a benefit of quinolones over macrolides. OBJECTIVE: To compare time to clinical stability (TCS) and length of hospital stay (LOS) in patients with Legionella pneumonia who were treated with levofloxacin (LVX) compared to those treated with newer macrolides. DESIGN: An analysis of patients with Legionnaires' disease from the Community-Acquired Pneumonia Organization database was performed. Patients were diagnosed with CAP using radiographic and clinical criteria, while Legionella was detected by urinary antigen or sputum culture. All patients received a macrolide (azithromycin or clarithromycin) or LVX. TCS was defined as the time from hospital admission to candidacy for switch to oral therapy. RESULTS: A total of 39 patients were included for analysis. The mean TCS for the macrolide group was 5.1 days vs. 4.3 days for the LVX group (P = 0.43). The mean LOS for the macrolide group was 12.7 days vs. 8.9 days for the quinolone group (P = 0.10). CONCLUSION: LOS and TCS were not statistically different between the macrolide and the LVX groups in treating CAP due to Legionella, despite trends in both outcomes favoring LVX.


Disseminated Legionella pneumophila infection in an immunocompromised patient treated with tigecycline

Valve K, Vaalasti A, Anttila VJ, Vuento R.

Department of Internal Medicine, Tampere University Hospital, Teiskontie 35, Tampere, Finland.

Scand J Infect Dis. 2010;42(2):152-5.

ABSTRACT: We describe an immunocompromised patient with disseminated Legionella pneumophila infection. A chronic leg ulcer was probably the port of entry for the infection. Treatment required several operations and prolonged antimicrobial treatment. To our knowledge, this is the first case report of Legionella soft tissue infection and pneumonia treated with tigecycline.


Suspected Legionella-induced perimyocarditis in an adult in the absence of pneumonia: a rare clinical entity

Burke PT, Shah R, Thabolingam R, Saba S.

Providence Heart Institute, Providence Hospital, Southfield, Michigan 48075, USA.

Tex Heart Inst J. 2009;36(6):601-3.

ABSTRACT: Legionella infection can manifest itself in many clinical forms, most commonly as pneumonia, but rarely in the form of myocardial involvement. Legionella with myocardial involvement independent of pneumonia is almost never seen in the adult population and therefore is cited only a handful of times in the medical literature. When reported, Legionella carditis itself typically occurs as an isolated pericarditis with effusion. Cases of isolated Legionella with myocardial involvement, but without associated pneumonia, have been reported among children. To our knowledge, there are no reported cases of Legionella myocarditis and pericarditis presenting concurrently with or without pneumonia, in either an adult or a pediatric population. Herein, we report a rare manifestation of Legionella pneumophila-induced perimyocarditis (strongly suspected, if not incontrovertibly proved) in an adult, in the absence of pneumonia.


Lung abscess caused by legionella species: implication of the immune status of hosts

Yu H, Higa F, Koide M, Haranaga S, Yara S, Tateyama M, Li H, Fujita J.

Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases (First Department of Internal Medicine), Faculty of Medicine, University of the Ryukyus, Okinawa, China.

Intern Med. 2009;48(23):1997-2002.

ABSTRACT: Legionella pneumonia typically presents as lobar pneumonia with multiple-lobe involvement, but Legionella lung abscess is rare. To identify the predisposing factors for Legionella abscess, we analyzed 62 of the 79 case reports on Legionella abscess found in literature; 28 (45.2%) were of hospital-acquired infection and 28 (45.2%), community-acquired infection. Seventeen patients (27.4%) died. L. pneumophila serogroup 1 was the most common, but other serogroups of L. pneumophila, L. micdadei, L. bozemanii, L. dumoffii, and L. maceachernii were also isolated from the abscess. Corticosteroids were administered for underlying diseases to 43 (69.4%) patients. Peripheral neutrophil counts were higher in patients with abscess than in those with only pulmonary infiltration. In certain cases, Legionella abscess developed during neutropenia recovery. However, lymphocyte counts were low in most cases. Clinical factors like corticosteroid treatment, which causes impaired cellular immunity and subsequent neutrophil accumulation in the lesion, might function as predisposing factors for Legionella abscess.


Non-invasive positive pressure ventilation for a severe legionella pneumonia case

Eryüksel E, Karakurt S, Balci M, Celikel T.

Department of Chest Diseases and Intensive Care, Faculty of Medicine, Marmara University, Istanbul, Turkey.

Tuberk Toraks. 2009;57(3):348-51

ABSTRACT: Legionella pneumonia has a serious clinical course and requires treatment at intensive care unit. The need for mechanical ventilation is one of the determinants of prognosis. Mortality rate is higher in patients treated with mechanical ventilation. Non-invasive positive pressure ventilation (NPPV) provides mechanical ventilation without endotracheal intubation and decreases the incidence of ventilator associated pneumonia. It is a treatment modality for patients with hypoxia due to community acquired pneumonia. The present case was admitted to intensive care unit with a diagnosis of legionella pneumonia, and his hypoxemic respiratory failure was successfully treated with NPPV.


Legionella-induced sudden hearing loss: a rare complication

Nolte JE, Altman A, Szyper-Kravitz M, Shoenfeld Y, Zimlichman E.

Infection 2009 Aug;37(4):377-8.



Legionella as a cause of hyperpyrexia

St Clair M, Crowley MJ, Sexton D.

Clin Infect Dis. 2009 Aug 15;49(4):646-7



Exanthema in Legionnaires' disease mimicking a severe cutaneous drug reaction

Ziemer M, Ebert K, Schreiber G, Voigt R, Sayer HG, Marx G.

Department of Dermatology, Friedrich Schiller University of Jena, Jena, Germany.

Clin Exp Dermatol. 2009 Jul;34(5):e72-4.

ABSTRACT: Legionnaires' disease is an acute bacterial infection, generally caused by Legionella pneumophila, which primarily involves the lower respiratory tract, although it is often associated with multisystemic extrapulmonary features. Cutaneous features are very uncommon and may include erythematous or petechial, macular or maculopapular lesions. We report a male patient who expressed all features of a severe lobular pneumonia. Over the course of the disease the patient developed a livid erythematous, maculopapular exanthem rapidly extending over the entire body. Given the rapid development and target-like appearance of the skin lesions with extensive skin involvement and blister formation, the initial diagnosis was that of a severe cutaneous drug reaction. However, histological examination of biopsy did not confirm this diagnosis, but instead was suspicious for a viral exanthem or a more aggressive inflammatory response due to sensitization to bacterial antigens. L. pneumophila infection was verified during the course of the disease.


Mycotic Aortic Aneurysm Associated with Legionella anisa

Tanabe M, Nakajima H, Nakamura A, Ito T, Nakamura M, Shimono T, Wada H, Shimpo H, Nobori T, Ito M.

Department of Cardiology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.

J Clin Microbiol. 2009 Jul;47(7):2340-3.

ABSTRACT: Legionella anisa is rarely associated with human disease. Its gene was identified by broad-range PCR in whole blood and excised tissue from a patient with a culture-negative mycotic aneurysm and was considered as a possible pathogen. This case report is potentially useful for the future diagnosis of intravascular infection.


Treatment strategies for Legionella infection

Pedro-Botet ML, Yu VL.

Universitat Autónoma de Barcelona, Badalona, Spain.

Expert Opin Pharmacother. 2009 May;10(7):1109-21.

ABSTRACT: Given the nonspecific clinical manifestations of Legionnaires' disease and the high mortality of untreated Legionnaires' disease, we recommend routine use of Legionella testing, especially the Legionella urinary antigen test, for all patients with community-acquired pneumonia. This includes patients with ambulatory pneumonia and hospitalized children. Legionella cultures should be more widely available, especially in hospitals where the drinking water is colonized with Legionella. Azithromycin or levofloxacin can be considered as first-line therapy. Other antibiotics including tetracyclines, tigecycline, other fluoroquinolones and other macrolides (especially clarithromycin) are also effective. The clinical response of quinolones may be somewhat more favorable compared to macrolides, but the outcome is similar. If the Legionnaires' disease is hospital-acquired, culturing of the hospital drinking water for Legionella is indicated.


"My foot hurts": a flare of rheumatoid arthritis?

Dugar M, Rankin WA, Rowe E, Smith MD.

Flinders Medical Centre, Adelaide, SA, Australia.

Med J Aust. 2009 Apr 6;190(7):392-3.

ABSTRACT: A 56-year-old man with a history of rheumatoid arthritis presented with a 2-day history of worsening pain in his left foot. Treatment with high-dose steroids was of no benefit, hence a diagnosis of septic arthritis was considered. However, the patient's condition deteriorated despite empirical antibiotic therapy. Following persistent investigation, the cause was identified as a fastidious Legionella longbeachae infection, and appropriate antibiotic therapy led to complete resolution of the sepsis. This emphasises the importance of considering infections with atypical organisms in patients on immunosuppressive therapy.


Prognostic value of procalcitonin in Legionella pneumonia

Haeuptle J, Zaborsky R, Fiumefreddo R, Trampuz A, Steffen I, Frei R, Christ-Crain M, Müller B, Schuetz P.

Department of Internal Medicine, University Hospital Basel, Basel, Switzerland.

Eur J Clin Microbiol Infect Dis. 2009 Jan;28(1):55-60.

ABSTRACT: The diagnostic reliability and prognostic implications of procalcitonin (PCT) (ng/ml) on admission in patients with community-acquired pneumonia (CAP) due to Legionella pneumophila are unknown. We retrospectively analysed PCT values in 29 patients with microbiologically proven Legionella-CAP admitted to the University Hospital Basel, Switzerland, between 2002 and 2007 and compared them to other markers of infection, namely, C-reactive protein (CRP) (mg/l) and leukocyte count (10(9)/l), and two prognostic severity assessment scores (PSI and CURB65). Laboratory analysis demonstrated that PCT values on admission were >0.1 in over 93%, >0.25 in over 86%, and >0.5 in over 82% of patients with Legionella-CAP. Patients with adverse medical outcomes (59%, n = 17) including need for ICU admission (55%, n = 16) and/or inhospital mortality (14%, n = 4) had significantly higher median PCT values on admission (4.27 [IQR 2.46-9.48] vs 0.97 [IQR 0.29-2.44], p = 0.01), while the PSI (124 [IQR 81-147] vs 94 [IQR 75-116], p = 0.19), the CURB65 (2 [IQR 1-2] vs 1 [1-3], p = 0.47), CRP values (282 [IQR 218-343], p = 0.28 vs 201 [IQR 147-279], p = 0.28), and leukocyte counts (12 [IQR 10-21] vs 12 [IQR 9-15], p = 0.58) were similar. In receiver operating curves, PCT concentrations on admission had a higher prognostic accuracy to predict adverse outcomes (AUC 0.78 [95%CI 0.61-96]) as compared to the PSI (0.64 [95%CI 0.43-0.86], p = 0.23), the CURB65 (0.58 [95%CI 0.36-0.79], p = 0.21), CRP (0.61 [95%CI 0.39-0.84], p = 0.19), and leukocyte count (0.57 [95%CI 0.35-0.78], p = 0.12). Kaplan-Meier curves demonstrated that patients with initial PCT values above the optimal cut-off of 1.5 had a significantly higher risk of death and/or ICU admission (log rank p = 0.003) during the hospital stay. In patients with CAP due to Legionella, PCT levels on admission might be an interesting predictor for adverse medical outcomes.


Is activity against "atypical" pathogens necessary in the treatment protocols for community-acquired pneumonia? Issues with combination therapy

Bartlett JG.

Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA.

Clin Infect Dis. 2008 Dec 1;47 Suppl 3:S232-6.

ABSTRACT: The "atypical pathogens" reviewed include Legionella pneumophila, Chlamydophilia pneumoniae, and Mycoplasma pneumoniae. Urinary antigen tests are the most frequently used tests for Legionella species and show good specificity and reasonable sensitivity. For M. pneumoniae, detection of immunoglobulin M, used for the past decade, has substantially improved diagnostic specificity and has simplified testing. For C. pneumoniae, there is no consensus on a simplified test that can be commonly used, and the reported results, with the use of tests that have not been well validated for diagnostic accuracy, show great variation in prevalence. With regard to therapeutic trials, 3 meta-analyses have recently addressed the issue of clinical outcome with or without antibiotics directed against atypical pathogens (macrolides or fluoroquinolones vs. beta-lactam agents). These analyses have not been able to demonstrate any clinical benefit, except in a subset analysis of infections caused by L. pneumophila. Nevertheless, multiple studies from the 1950s and 1960s supported a clinical benefit of tetracycline or erythromycin treatment for infections caused by M. pneumoniae. The largest uncontrolled review of antibiotic treatment for hospitalized patients with community-acquired pneumonia demonstrated a clear benefit from the use of macrolides plus cephalosporins or fluoroquinolones, compared with the use of beta-lactams alone, although these data support a potential role for atypical agents, because other potential explanations make drawing conclusions difficult. With regard to future studies, it is noted that the standard of care in the United States, Canada, and some other countries is routine use of agents to treat infection with atypical pathogens, which makes the conduct of controlled trials to address these issues ethically difficult and practically impossible. Additional limitations are the difficulty in diagnostic testing for C. pneumoniae and the importance of rapid institution of therapy for patients severely ill enough to require hospitalization. These observations introduce substantial ethical and logistical barriers to studies of specific agents, except by retrospective analyses.


Could it be Legionella?

Darby J, Buising K.

Infectious Diseases Unit, St Vincent's Hospital, Fitzroy, Victoria.

Aust Fam Physician. 2008 Oct;37(10):812-5.

ABSTRACT: BACKGROUND: Community acquired pneumonia is a common condition presenting to general practitioners and emergency departments across Australia. Legionella is one of many pathogens responsible for community acquired pneumonia. Cases of Legionella may occur sporadically or as part of an outbreak. OBJECTIVE: This article describes the clinical manifestations of Legionella infection and provides clinicians with an approach to its diagnosis and management. DISCUSSION: Legionella infection is typically associated with community acquired pneumonia, which can be severe. Features pointing to Legionella as a cause of pneumonia include the presence of gastrointestinal symptoms, especially diarrhoea; neurological symptoms, especially confusion; fever up to 40 degrees C; hyponatraemia; and hepatic dysfunction. However, none of these is required to make the diagnosis. Sometimes nonrespiratory symptoms can predominate. Diagnosis requires the use of special tests specific for Legionella, the most clinically useful being urinary antigen tests and serology. Recommended treatments include macrolide therapy or doxycycline.


Pathological evidence of rhabdomyolysis-induced acute tubulointerstitial nephritis accompanying Legionella pneumophila pneumonia

Shimura C, Saraya T, Wada H, Takata S, Mikura S, Yasutake T, Kato J, Kato A, Yamamoto M, Watanabe M, Yokoyama T, Kurai D, Ishii H, Aoshima M, Yamada A, Goto H.

Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.

J Clin Pathol. 2008 Sep;61(9):1062-3.

ABSTRACT: A case of Legionella pneumophila pneumonia with rhabdomyolysis-induced acute tubulointerstitial nephritis (ATIN) and prolonged renal dysfunction is presented. The patient was a 54-year-old man, admitted with high-grade fever, ataxia and muscle dysfunction; chest roentgenogram showed multilobular infiltrations. L pneumophila was detected in his sputum and urine, by PCR and by culture, and L pneumophila pneumonia was diagnosed. Despite antimicrobial treatment, he developed renal failure and rhabdomyolysis. Renal biopsy showed the presence of myoglobin casts that occluded the distal tubuli and tubulointerstitial nephritis, leading to the diagnosis of rhabdomyolysis-induced ATIN. Renal function subsequently normalised, and he was discharged. This is believed to be the first pathological evidence of involvement of rhabdomyolysis in legionellosis-associated ATIN.


Adrenal gland hemorrhage in patients with fatal bacterial infections

Guarner J, Paddock CD, Bartlett J, Zaki SR.

Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.

Mod Pathol. 2008 Sep;21(9):1113-20.

ABSTRACT: A wide spectrum of adrenal gland pathology is seen during bacterial infections. Hemorrhage is particularly associated with meningococcemia, while abscesses have been described with several neonatal infections. We studied adrenal gland histopathology of 65 patients with bacterial infections documented in a variety of tissues by using immunohistochemistry. The infections diagnosed included Neisseria meningitidies, group A streptococcus, Rickettsia rickettsii, Streptococcus pneumoniae, Staphylococcus aureus, Ehrlichia sp., Bacillus anthracis, Leptospira sp., Clostridium sp., Klebsiella sp., Legionella sp., Yersinia pestis, and Treponema pallidum. Bacteria were detected in the adrenal of 40 (61%) cases. Adrenal hemorrhage was present in 39 (60%) cases. Bacteria or bacterial antigens were observed in 31 (79%) of the cases with adrenal hemorrhage including 14 with N. meningitidis, four with R. rickettsii, four with S. pneumoniae, three with group A streptococcus, two with S. aureus, two with B. anthracis, one with T. pallidum, and one with Legionella sp. Bacterial antigens were observed in nine of 26 non-hemorrhagic adrenal glands that showed inflammatory foci (four cases), edema (two cases), congestion (two cases), or necrosis (one case). Hemorrhage is the most frequent adrenal gland pathology observed in fatal bacterial infections. Bacteria and bacterial antigens are frequently seen in adrenal glands with hemorrhage and may play a pathogenic role. Although N. meningitidis is the most frequent bacteria associated with adrenal gland pathology, a broad collection of bacteria can also cause adrenal lesions.


Guillain-Barré syndrome associated with Legionella infection

Akyildiz B, Gümüs H, Kumandas S, Coskun A, Baykan A, Yikilmaz A, Kara I, Okur A.

Department of Pediatric Intensive, Erciyes University Medical Faculty, Kayseri, Turkey.

J Trop Pediatr. 2008 Aug;54(4):275-7.

ABSTRACT: This is the first report of Guillain-Barré syndrome (GBS) related to Legionnella pneumophilia infection. A 13-year-old boy presented with acute dysphagia and dyspnea. He lived in a rural area and had a history of drinking potable deep-hole water. The patient was intubated because of increased respiratory distress. A positive direct fluoresein antigen test confirmed L. pneumophilia infection in BAL. One week after the first admission, acute weakness was noticed including the lower extremities and was more prominent in the distal than the proximal portions. GBS was considered as the initial diagnosis. Tests for all causes known to trigger GBS were negative. Specific serology for L. pneumophilia IgG was positive. He was treated with intravenous immunoglobulins and discharged with minor weakness and difficulty in walking in the second month. On the basis of this case, L. pneumophilia should be included in the etiologic spectrum of GBS.


Atypical pneumonias: current clinical concepts focusing on Legionnaires' disease

Cunha BA.

Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501, USA Tel: +1 516 663 2505; fax: +1 516 663 2753.

Curr Opin Pulm Med. 2008 May;14(3):183-94.

ABSTRACT: PURPOSE OF REVIEW: This review provides clinicians with an overview of the clinical features of the atypical pneumonias. Atypical community-acquired pneumonia pathogens cause systemic infections with pneumonia. The key to the clinical diagnosis of atypical pneumonias depends on recognizing the characteristic pattern of extrapulmonary organ involvement different for each pathogen. As Legionella is likely to present as severe pneumonia and does not respond to beta-lactams, it is important to presumptively diagnose Legionnaires' disease clinically so that Legionella coverage is included in empiric therapy. This study reviews the clinical features and nonspecific laboratory markers of atypical pathogens, focusing on Legionnaires' disease. RECENT FINDINGS: Case reports/outbreaks increase our understanding of Legionnaires' disease transmission. Both Mycoplasma pneumoniae and Chlamydophilia pneumoniae may cause asthma. Antimicrobial therapy of Chlamydophilia pneumoniae/Mycoplasma pneumoniae is important to decrease person-to-person spread and to decrease potential long-term sequelae. SUMMARY: Atypical pulmonary pathogens cause systemic infections accompanied by a variety of characteristic extrapulmonary features. Clinically, it is possible to differentiate Legionnaires' disease from the other typical/atypical pneumonias. Rapid clinical diagnosis of atypical pathogens, particularly Legionnaires' disease, is important in selecting effective empiric therapy and prompting definitive laboratory testing.


Early diagnosis of lower respiratory tract infections (point-of-care tests)

Charles PG.

Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia.

Curr Opin Pulm Med. 2008 May;14(3):176-82.

ABSTRACT: PURPOSE OF REVIEW: Respiratory tract infections are a common reason for prescribing antibiotics, although not all of these infections require such therapy. Rapid diagnosis of etiology using point-of-care tests is a potentially useful way of reducing prescriptions of both unnecessary and unnecessarily broad-spectrum antibiotics. This can also lead to the facilitation of appropriate infection control measures to prevent spread of respiratory viruses within institutions. RECENT FINDINGS: Point-of-care tests are available for diagnosing influenza, respiratory syncytial virus, Streptococcus pneumoniae, and Legionella infections using easily obtainable specimens. Their main benefit is that results can be obtained in about 15 min with reasonable accuracy. In many situations, however, it is still important to confirm diagnosis with more accurate but slower tests such as bacterial cultures with antibacterial susceptibility testing or viral polymerase chain reaction testing. SUMMARY: Although the sensitivities of many of the rapid diagnostic tests are moderate, when used at the time of initial consultation, they have the potential to reduce costs, length of stay, secondary spread of respiratory viruses, and inappropriate antibiotic prescribing.


Severe Legionella pneumonia successfully treated by independent lung ventilation with intrapulmonary percussive ventilation

Fujita M, Tsuruta R, Oda Y, Kaneda K, Miyauchi T, Kasaoka S, Maekawa T.

The Advanced Medical Emergency and Critical Care Center, Yamaguchi University Hospital, Yamaguchi, Japan.

Respirology. 2008 May;13(3):475-7.

ABSTRACT: A case of severe Legionella pneumonia was successfully treated by independent lung ventilation (ILV) with intrapulmonary percussive ventilation (IPV). A 57-year-old man with lobar pneumonia was intubated and mechanically ventilated because of his deteriorating respiratory status. The diagnosis of Legionella pneumonia was made on the fourth day after admission and appropriate antibiotic therapy was commenced. On the fifth hospital day, ILV was commenced because the right unaffected lung was over-distended, his haemodynamic state was unstable and his left lung was producing copious amounts of purulent sputum. His right lung was ventilated and his left lung was treated with IPV owing to the existence of massive atelectasis. After treatment with antibiotics and ILV combined with IPV, his respiratory and haemodynamic status gradually improved. On the tenth day after admission, ILV was changed to conventional bilateral ventilation. The patient was extubated on the sixteenth hospital day and discharged from the intensive care unit 30 days after admission. The combination of ILV and IPV was therapeutically effective during the acute phase of unilateral severe Legionella pneumonia. 


Legionella maceachernii Soft Tissue Infection

Chee CE, Baddour LM.

From the Department of Medicine (cec, lmb), Division of Infectious Diseases (lmb), Mayo Clinic College of Medicine, Rochester, Minnesota.

Am J Med Sci. 2007 Nov;334(5):410-3.

ABSTRACT; Soft tissue infection caused by Legionella spp. is rare. Infection due to Legionella maceachernii has only been described in 5 cases and none of them had soft tissue infection; they were immunocompromised hosts who presented with pneumonia. To our knowledge, this is the first case report of L. maceachernii soft tissue infection.


Tuberculosis and Legionella pneumophila pneumonia in a patient receiving anti-tumour necrosis factor-alpha (anti-TNF-alpha) treatment

Mancini G, Erario L, Gianfreda R, Oliva A, Massetti AP, Mastroianni CM, Vullo V.

Department of Infectious and Tropical Diseases, Sapienza University, Rome, Italy.

Clin Microbiol Infect. 2007 Oct;13(10):1036-7



Activity of iclaprim against Legionella pneumophila

Morrissey I, Hawser S.

GR Micro Ltd, 7-9 William Road, London NW1 3ER, UK.

J Antimicrob Chemother. 2007 Oct;60(4):905-6.



Legionella pneumophilia serogroup 1 pneumonia recurrence postbone marrow transplantation

Gonzalez IA, Martin JM.

Department of Pediatrics, Division of Infectious Diseases, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine Pittsburgh, PA 15213, USA.

Pediatr Infect Dis J. 2007 Oct;26(10):961-3.

ABSTRACT: Recurrences of Legionnaires' disease have been reported uncommonly and rarely in immunocompromised children. We describe a 9-year-old girl with 2 episodes of culture proven infection with Legionella pneumophila. First episode occurred during induction chemotherapy for acute lymphoblastic leukemia and the second shortly after the bone marrow transplant.


Community-acquired lung abscess caused by Legionella micdadei in a myeloma patient receiving thalidomide treatment

Girard LP, Gregson DB.

Division of Medicine, University of Calgary, 9-3535 Research Road NW, Calgary, Alberta, Canada T2L 2K8.

J Clin Microbiol. 2007 Sep;45(9):3135-7.

ABSTRACT: Legionella infection causes 2 to 14% of community-acquired pneumonia (CAP). Legionella micdadei constitutes <1% of these infections. We describe a case of cavitary L. micdadei CAP in a myeloma patient receiving thalidomide treatment. The importance of considering pneumonia and problems in diagnosing pneumonia caused by L. micdadei in this patient population are reviewed.


Legionella bozemanii pulmonary abscess in a pediatric allogeneic stem cell transplant recipient

Miller ML, Hayden R, Gaur A.

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Pediatr Infect Dis J. 2007 Aug;26(8):760-2.

ABSTRACT: Legionella spp. infections are often considered in the differential diagnosis of pneumonia in adults. This case report describes a pediatric stem cell transplant recipient presenting with cavitary pulmonary disease secondary to Legionella bozemanii infection. Also highlighted with this atypical clinical presentation are challenges in diagnosing legionellosis and concerns of increased vulnerability for such infections when severely immunocompromised patients are changed to nontrimethoprim-sulfamethoxazole Pneumocystis jiroveci pneumonia prophylaxis.


Activity of telithromycin and comparators against isolates of Legionella pneumophila collected from patients with community-acquired respiratory tract infections: PROTEKT Years 1-5

Dunbar LM, Farrell DJ.

LSU Health Science Center, New Orleans, LA 70112, USA.

Clin Microbiol Infect. 2007 Jul;13(7):743-6.

ABSTRACT: The in-vitro activity of telithromycin and comparator antibacterial agents was determined against clinical isolates of Legionella pneumophila collected in the PROTEKT surveillance study. In total, 133 isolates were collected between 1999 and 2004 from 13 countries (Australia, Belgium, Czech Republic, France, Germany, Hungary, Ireland, Italy, Japan, Portugal, Spain, Sweden and the USA). MICs were determined by broth microdilution. Telithromycin maintained activity between Year 1 (MIC(90) 0.015 mg/L) and Year 5 (MIC(90) 0.03 mg/L), as did the comparator antibacterial agents. Telithromycin appears to be a candidate for coverage of legionellosis in the empirical treatment of community-acquired respiratory tract infection.


Cavitary Legionella pneumonia in a patient with immunodeficiency due to Hyper-IgE syndrome

Di Stefano F, Verna N, Di Gioacchino M.

Department of Internal Medicine, Respiratory Medicine Unit, Immunology and Allergology Unit, University G. d'Annunzio, Chieti, Italy.

J Infect. 2007 Mar;54(3):e121-3.

ABSTRACT: We report about a 35-year-old man with a cavitary legionella pneumonia who had a history of chronic eczematoid lesions since infancy, recurrent skin and lung infections and a very high total IgE level. We carried out further investigations and made a diagnosis of a primary immunodeficiency classified in the Hyper-IgE syndromes. Cavitation of legionella pneumonia may become fairly common in immunocompromised patients, while is found rarely among immunocompetent hosts.


Legionella pneumophila aortitis in a heart transplant recipient

Guyot S, Goy JJ, Gersbach P, Jaton K, Blanc DS, Zanetti G.

Service of Infectious Diseases, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Transpl Infect Dis. 2007 Mar;9(1):58-9.

ABSTRACT: We describe the case of a patient with a culture-proven infection of the ascending aorta caused by Legionella pneumophila 16 months after cardiac transplantation. Serology follow-up and surveillance culture of the hospital water supply suggested a nosocomial acquisition of the infection during the post-transplantation period. The diagnosis was made after 5 months of recurrent unexplained febrile episodes. A Teflon ring implanted around the aortic suture line during the intervention may have contributed to the unusual localization of the infection. The patient was successfully treated with antibiotics and aortic reconstruction.


Reactive Legionella pneumophila arthritis diagnosed by polymerase chain reaction

Naito T, Suda T, Saga K, Horii T, Chida K.

Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.

Rheumatol Int. 2007;27(4):415-6.



Legionnaire's pneumonia: is there really an interstitial disease?

Godet C, Frat JP, Le Moal G, Roblot F, Michalakis G, Cabon E, Tasu JP.

Service de Maladies Infectieuses, CHU la Milétrie, rue de la milétrie, 86021 Poitiers, France.

Eur J Radiol. 2007 Jan;61(1):150-3.

ABSTRACT: OBJECTIVE: Legionella pneumonia is usually classified as "atypical pneumonia", which suggests a predominance of interstitial patterns in chest X-rays. Based on a selection of recent clinical cases and a brief review of the literature, the aim of the study is to clarify, how far the actual radiological findings would be consistent with these expectations. PATIENTS AND METHODS: A retrospective analysis of 18 epidemic personal cases and a review of the literature data were performed to describe the chest X-ray findings of Legionella pneumophila (LP) community acquired pneumonia. X-ray review was performed simultaneously and in consensus by two radiologists (J.P.T., E.C.) and a physician (C.G.). RESULTS: From our series, 17 patients had an abnormal chest X-ray on admission. Among these pathological X-ray cases, infiltrates were more often confluent (n=16), or patchy (n=7), rather than interstitial (n=1). Fifteen patients had infiltrates involving the lower lung fields. Bilateral distribution of abnormalities and pleural effusion were each observed in three cases. Radiological findings deteriorated between the second and seventh days following admission, particularly in the form of patchy infiltrates with pleural effusion. The review of the literature is consistent with these findings, by reporting prevalent confluent or patchy infiltrates. CONCLUSIONS: These findings are consistent with the physiopathological particularity of this affection and incite us to avoid the classification "atypical pneumonia" in radiologic terminology. This term is more appropriate for clinical and microbiological use.


Intravenous ciprofloxacin versus erythromycin in the treatment of Legionella pneumonia

Haranaga S, Tateyama M, Higa F, Miyagi K, Akamine M, Azuma M, Yara S, Koide M, Fujita J.

Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases (First Department of Internal Medicine), Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.

Intern Med. 2007;46(7):353-7.

BACKGROUND: Erythromycin (EM) and rifampicin (RFP) have mainly been used to treat patients with Legionella pneumonia. Since intravenous ciprofloxacin (CPFX) became available in Japan from 2000, many reports have been published detailing successful treatment of Legionella pneumonia with CPFX. In this study, we compared the evolution of patients with Legionella pneumonia treated with CPFX to those treated with EM. METHODS: The study included nine patients treated with CPFX and eighteen patients treated with EM. Diagnosis of these patients was made by culture, PCR, urinary antigen assay or a serological method. A comparison was made of the patients' characteristics, severity of pneumonia, efficacy of each agent and the clinical course. RESULTS: No significant differences were observed between the two groups, in regard to age, gender, underlying disease or severity of pneumonia. In addition, the period of time from onset of the disease until appropriate therapy did not differ significantly between the two groups. In the CPFX group, all of the patients were cured and in the EM group 16 out of the 18 patients were cured. Although there were no significant differences, the time to apyrexia, normalization of leukocytosis and a 50% decrease in C-reactive protein (CRP) occurred within a relatively shorter time frame in the CPFX group than in the EM group (3.5 versus 4 days, 4 versus 5.2 days, and 2.9 versus 10.3 days, respectively). And, the duration of antibiotic treatment in the CPFX group was significantly shorter than in the EM group. CONCLUSION: CPFX was as effective as erythromycin in the treatment of Legionella pneumonia. The effects of treatment may appear relatively earlier and the duration of treatment was significantly shorter in patients treated with CPFX therapy than with EM therapy.


Current clinical management of Legionnaires' disease

Garcia-Vidal C, Carratalà J.

Infectious Disease Service, IDIBELL-Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de llobregat, Barcelona, Spain.

Expert Rev Anti Infect Ther. 2006 Dec;4(6):995-1004.

ABSTRACT: Legionella pneumophila is increasingly recognized as a cause of both sporadic and epidemic community-acquired pneumonia. Clinical manifestations of Legionnaires' disease are not specific and current diagnostic scores are of limited use. Urinary antigen detection is an effective test for rapid diagnosis of infection caused by L. pneumophila serogroup 1. Improved outcomes regarding the time to defervescence, development of complications and length of stay, have been recently observed for patients treated with levofloxacin monotherapy. Current case-fatality rates for hospitalized patients with community-acquired Legionella pneumonia are lower than those traditionally reported for this infection. Effective preventive strategies are needed.


Emergence of Legionella pneumophila pneumonia in patients receiving tumor necrosis factor-alpha antagonists

Tubach F, Ravaud P, Salmon-Céron D, Petitpain N, Brocq O, Grados F, Guillaume JC, Leport J, Roudaut A, Solau-Gervais E, Lemann M, Mariette X, Lortholary O; Recherce Axée sur la Tolérance des Biothérapies Group.

Université Paris 7, Faculté de Medecine, Paris, France.

Clin Infect Dis. 2006 Nov 15;43(10):e95-100.

BACKGROUND: Patients treated with tumor necrosis factor-alpha (TNF-alpha) antagonists have an increased risk of infection, but infection due to Legionella pneumophila has rarely been described in patients receiving such therapy. METHODS: A registry involving 486 clinical departments in France was designed by a multidisciplinary group (Recherche Axée sur la Tolérance des Biothérapies [RATIO]) to collect data on opportunistic and severe infections occurring in patients treated with TNF-alpha antagonists. All cases are reported to RATIO in accordance with national health authorities and validated by infectious disease experts. The legionellosis rate among patients treated with TNF-alpha antagonists was compared with the rate in France overall. RESULTS: We report a 1-year consecutive series of 10 cases of L. pneumophila pneumonia in France in 2004, including 6 cases treated with adalimumab, 2 treated with etanercept, and 2 treated with infliximab. The median patient age was 51 years (range, 40-69 years). Eight patients were treated for rheumatoid arthritis, 1 was treated for cutaneous psoriasis, and 1 was treated for pyoderma gangrenosum. The median duration of TNF-alpha antagonist treatment at onset of infection was 38.5 weeks (range, 3-73 weeks). Eight patients were receiving concomitant treatment with corticosteroids, and 6 were receiving treatment with methotrexate. The relative risk of legionellosis when receiving treatment with a TNF-alpha antagonist, compared with the relative risk in France overall, was estimated to be between 16.5 and 21.0. We also report a second episode of confirmed legionellosis following the reintroduction of infliximab therapy. CONCLUSIONS: L. pneumophila pneumonia is a potentially severe but curable infection that might complicate anti-TNF-alpha therapy. In patients receiving anti-TNF-alpha who develop pneumonia, legionellosis should be systematically investigated, and first-line antibiotic therapy should be efficient against L. pneumophila.


Impact of rifampicin addition to clarithromycin in Legionella pneumophila pneumonia

Grau S, Antonio JM, Ribes E, Salvadó M, Garcés JM, Garau J.

Pharmacy Department, Hospital del Mar, Passeig Marítim, 25-29, 08003 Barcelona, Spain.

Int J Antimicrob Agents. 2006 Sep;28(3):249-52.

ABSTRACT: We evaluated the effectiveness and safety of rifampicin addition to clarithromycin in the treatment of Legionnaires' disease. An observational cohort study was conducted on patients assigned to a Legionnaires' disease outbreak. Of 32 patients with confirmed Legionella pneumonia, 11 received clarithromycin monotherapy and 21 received combination therapy of clarithromycin with rifampicin. Both groups had similar baseline characteristics and all patients were cured. Patients who received rifampicin had a 50% longer length of stay (P=0.035) and a trend towards higher bilirubin levels (P=0.053). Length of stay was directly correlated with the duration of rifampicin treatment (P=0.001). Combination therapy of clarithromycin and rifampicin had no additional benefit compared with clarithromycin monotherapy and could prolong the length of stay owing to possible negative drug interactions that could also affect other antibiotics.


Multiple pulmonary abscesses caused by Legionella pneumophila infection in an infant with croup

Myers C, Corbelli R, Schrenzel J, Gervaix A.

Hôpitaux Universitaires de Genève, Department of Pediatrics.

Pediatr Infect Dis J. 2006 Aug;25(8):753-4.

ABSTRACT: Legionella infections are uncommon in childhood. We report the case of an infant who developed multiple pulmonary abscesses caused by Legionella pneumophila after receiving prolonged corticosteroid treatment of severe croup. Diagnosis was not suspected because immunosuppression was not initially considered. Caution should be used when prolonging high-dose corticosteroids in children with respiratory diseases.


Community-acquired pneumonia in Shanghai, China: microbial etiology and implications for empirical therapy in a prospective study of 389 patients

Huang HH, Zhang YY, Xiu QY, Zhou X, Huang SG, Lu Q, Wang DM, Wang F.

Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, 200040, People's Republic of China.

Eur J Clin Microbiol Infect Dis. 2006 Jun;25(6):369-374.

ABSTRACT: The aim of this multicenter study was to identify the causative pathogens of community-acquired pneumonia (CAP) in Shanghai, China, and to determine their susceptibility to antimicrobial agents. Pathogens obtained from 389 patients with documented CAP during 2001-2003 were identified by multiple diagnostic tools that included bacterial culture, polymerase chain reaction (PCR), and specific immunological assays. Susceptibility of the bacterial isolates was tested by the broth microdilution method. A specific pathogen was identified in 39.8% (155/389) of the patients: Haemophilus influenzae (n=80), Klebsiella spp. (n=15), Streptococcus pneumoniae (n=12), Staphylococcus aureus (n=6), Moraxella catarrhalis (n=1), other gram-negative organisms (n=9), and atypical pathogens that comprised Mycoplasma pneumoniae (n=42), Chlamydia pneumoniae (n=17), and Legionella pneumophila (n=2). Most H. influenzae isolates were susceptible to ampicillin (88.3%), and all were susceptible to macrolides. Of the S. pneumoniae isolates, 75% (9/12) were susceptible to penicillin, while 25% (3/12) were intermediately susceptible. H. influenzae and atypical pathogens are among the most important pathogens of CAP. Ampicillin, cephalosporins, and the newer fluoroquinolones can be used as empirical therapy for CAP in the Shanghai area. The efficacy of monotherapy with newer macrolides for CAP caused by S. pneumoniae requires further evaluation.


Successful treatment of Legionella maceachernii pneumonia after diagnosis by polymerase chain reaction and culture

van Dam AP, Pronk M, van Hoek B, Claas EC.

Leiden University Medical Ctr., Albinusdreef 2, 2300 RA Leiden, The Netherlands.

Clin Infect Dis. 2006 Apr 1;42(7):1057-9.



Pneumonitis caused by Legionella pneumoniae in a patient with rheumatoid arthritis treated with anti-TNF-alpha therapy (infliximab)

Li Gobbi F, Benucci M, Del Rosso A.

J Clin Rheumatol. 2005 Apr;11(2):119-20.



Extracorporeal membrane oxygenation for Legionnaires disease: a case report

Harris DJ, Duke GJ, McMillan J.

Intensive Care Department, The Northern Hospital, Epping, Victoria.

Crit Care Resusc. 2002 Mar;4(1):28-30.

A case of Legionella pneumonia, severe adult respiratory distress syndrome (ARDS) and multiple organ failure is described in a patient who required extracorporeal membrane oxygenation (ECMO) prior to transfer to a hospital with ECMO facilities. She eventually made a good recovery, highlighting the potential benefits of ECMO in patients with severe and refractory ARDS.


Brainstem involvement in Legionnaires' disease

Morelli N, Battaglia E, Lattuada P.

Department of Respiratory Medicine, Second University of Naples, Italy.

Infection. 2006 Feb;34(1):49-52.

ABSTRACT: OBJECTIVE: To report a case of Legionella pneumonia with unusual neurologic involvement. INTERVENTION: Chest X-ray, lumbar puncture, magnetic imaging of the brain, electroencephalography, audiometry, brainstem acoustic evoked potentials and institution of oral antibiotics and steroids. MAIN RESULT: Gradual clinical improvement of neurologic and pulmonary illness within 4 weeks. CONCLUSION: Legionellosis should be considered in the differential diagnosis of neurologic involvement in the setting of pneumonia.


Renal failure associated with Legionella pneumophila infection

Daram SR, Bastani B.

Department of Internal Medicine, Saint Joseph Regional Medical Center, Medical College of Wisconsin, USA.

Br J Hosp Med (Lond). 2006 Feb;67(2):100-1.



Uptake, transport, delivery, and intracellular activity of antimicrobial agents

Mandell GL.

Division of Infectious Diseases and International Medicine, University of Virginia Health System, Charlottesville, Virginia.

Pharmacotherapy. 2005 Winter;25(12):130S-3S.

ABSTRACT: Antibiotic interactions with cells, including polymorphonuclear neutrophils, may influence therapeutic outcomes. Selected microbes (e.g., Legionella pneumophila) may survive ingestion by polymorphonuclear neutrophils and are thus protected from the action of antimicrobial agents that remain extracellular. Antibiotics that penetrate the cell can kill these microbes. Certain antibiotics are concentrated inside phagocytes, and when the phagocyte migrates toward the site of infection, the antibiotic-loaded cell carries the active agent to the infecting microbes. Active antibiotic may be released when the short-lived phagocyte dies. Even microbes considered to be extracellular pathogens, such as pneumococci, may survive high concentrations of antibiotic by entering cells. Antibiotics that penetrate and are active in cells may aid in enhancing therapeutic outcomes and in eliminating the carrier state for some pathogens.


Legionnaires' disease associated with macular rash: two cases

Calza L, Briganti E, Casolari S, Manfredi R, Chiodo F, Zauli T.

Department of Clinical and Experimental Medicine, Section of Infectious Diseases, University of Bologna Alma Mater Studiorum, S. Orsola Hospital, Italy.

Acta Derm Venereol. 2005;85(4):342-4.

ABSTRACT: Legionnaires' disease is an acute bacterial infection, generally sustained by Legionella pneumophila, which involves primarily the lower respiratory tract, although it is often associated with multi-systemic extrapulmonary manifestations. Afflicted patients may sometimes have gastrointestinal symptoms, liver function abnormalities, renal failure or central nervous system complications, while cutaneous manifestations are very uncommon and may include erythematous, maculopapular or petechial skin lesions. Pathogenesis of skin involvement in the setting of Legionnaires' disease is still uncertain, but may involve toxic or immunological mechanisms. Two exceptional cases of Legionella pneumonia complicated by diffuse, macular rash in two adult women are described, in association with severe peripheral polyneuropathy and flaccid quadriplegia in one case.


Revised SWAB guidelines for antimicrobial therapy of community-acquired pneumonia

Schouten JA, Prins JM, Bonten MJ, Degener J, Janknegt RE, Hollander JM, Jonkers RE, Wijnands WJ, Verheij TJ, Sachs AP, Kullberg BJ.

Nijmegen University Centre for Infectious Diseases (NUCI) and Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.

Neth J Med. 2005 Sep;63(8):323-35.

ABSTRACT: The Dutch Working Party on Antibiotic Policy (SWAB) develops evidence-based guidelines, aimed at optimalisation of antibiotic use and limitation of the spread of antimicrobial resistance. A revision of the SWAB guideline for the treatment of community-acquired pneumonia (CAP), published in 1998, was considered necessary because of changes in resistance patterns and new insights into the epidemiology, diagnostics and treatment of CAP. In contrast to the former version, this guideline is transmural and has been drawn up according to the recommendations for evidence-based guideline development by a multidisciplinary committee consisting of experts from all relevant professional societies. The 'severity of disease' exhibited by the patient with pneumonia on admission is considered important for the choice of the optimum empirical treatment strategy. Severely ill patients are treated empirically with a drug directed against multiple potential pathogens, including Legionella spp. Classification according to 'severity of disease' can be accomplished with a validated scoring system (Pneumonia Severity Index or CURB-65 score) or pragmatically, based on the site of treatment: an outpatient setting, a clinical ward or an intensive care unit. The Legionella urine antigen test plays an important role in decisions on the choice of initial antibiotic treatment.


Empirical atypical coverage for inpatients with community-acquired pneumonia: systematic review of randomized controlled trials

Shefet D, Robenshtok E, Paul M, Leibovici L.

Department of Medicine E, Beilinson Campus, Rabin Medical Center, Petah-Tiqva, Israel.

Arch Intern Med. 2005 Sep 26;165(17):1992-2000.

BACKGROUND: Current guidelines of empirical antibiotic treatment for inpatients with community-acquired pneumonia recommend antibiotics whose spectrum covers intracellular (atypical) pathogens. No sufficient evidence exists to support the necessity of such coverage, whereas limiting it may reduce toxic effects, resistance, and expense. Our goal was to assess the efficacy of empirical coverage of atypical pathogens in terms of mortality and clinical and bacteriological success. METHODS: Systematic review and meta-analysis of randomized, controlled trials comparing treatment regimens with and without coverage of atypical pathogens. We searched MEDLINE, EMBASE, the Cochrane Library, and references. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled using the fixed-effects model. The primary outcome assessed was all-cause mortality. RESULTS: We included 24 trials encompassing 5015 patients. We found no studies of a drug without atypical coverage that compared it with the same drug supplemented with a drug with atypical coverage; nearly all compared a beta-lactam with a single quinolone or macrolide. There was no difference in mortality between the 2 arms (RR, 1.13 [95% CI, 0.82-1.54]). Regimens with coverage of atypical pathogens showed a trend toward clinical success and a significant advantage to bacteriological eradication. Both disappeared when evaluating methodologically high-quality studies alone. These regimens further showed a significant advantage in clinical success for Legionella pneumophila, whereas no advantage for pneumococcal pneumonia was seen. There was no difference between study arms in the frequency of total adverse events. CONCLUSION: Empirical antibiotic coverage of atypical pathogens in hospitalized patients with community-acquired pneumonia showed no benefit of survival or clinical efficacy in this synthesis of randomized trials.


Fluoroquinolones vs macrolides in the treatment of Legionnaires disease

Sabria M, Pedro-Botet ML, Gomez J, Roig J, Vilaseca B, Sopena N, Banos V; Legionnaires Disease Therapy Group.

Infectious Diseases Unit, Hospital Universitari Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Spain.

Chest. 2005 Sep;128(3):1401-5.

ABSTRACT: BACKGROUND: Erythromycin has been the treatment of choice for Legionnaires disease (LD). However, treatment failure and experimental evidence of its bacteriostatic effect have led to evaluation of new drugs such as fluoroquinolones. This study compared the evolution of patients with LD treated with macrolides and fluoroquinolones. METHODS: A prospective observational study was performed, and 130 patients from three centers were included. Diagnoses were made using Legionella urinary antigen assay in all patients. Patients receiving any antibiotic > 36 h before starting the study therapy were excluded. Group 1 included 76 patients who received macrolides (33 patients with erythromycin and 43 patients with clarithromycin), and group 2 included 54 patients treated with fluoroquinolones (50 patients with levofloxacin and 4 patients with ofloxacin). RESULTS: No significant differences were seen between the two groups regarding age, sex, smoking, alcohol intake, underlying diseases, or community/hospital acquisition. The time from onset of LD symptoms until the initiation of antibiotic treatment was 78.5 h and 92.7 h in groups 1 and 2, respectively (p = 0.1). Time to apyrexia was significantly longer in the macrolide group (77.1 h vs 48 h for groups 1 and 2, respectively; p = 0.000). There were no differences according to radiology, clinical complications, or mortality. Nevertheless, a trend to a longer hospital stay was observed in the macrolide group (9.9 days vs 7.6 days in groups 1 and 2, respectively; p = 0.09). CONCLUSIONS: Fluoroquinolones were as effective as erythromycin in the treatment of LD. It is of note that time to apyrexia was significantly shorter and hospital stay tended to be shorter in patients receiving fluoroquinolones.


Focal neurological manifestations in Legionellosis

Kulkarni KH, Thorat SB, Wagle SC, Khadilkar SV.

Department of Medicine, Bombay Hospital Institute of Medical Sciences, Mumbai.

J Assoc Physicians India. 2005 Aug;53:731-3.

ABSTRACT: Legionnaires' disease is an atypical pneumonia with protean multisystem manifestations. Neurological involvement in legionellosis is rare and tends to be among the presenting manifestations. We report a previously healthy young lady who developed focal sensory deficits and cerebellar dysfunction after clinical recovery from Legionella pneumonia. The care is unusual for the delayed appearance of striking focal sensory abnormalities and cerebellar dysfunction.


L. micdadei PVE successfully treated with levofloxacin/valve replacement: case report and review of the literature

Patel MC, Levi MH, Mahadevi P, Nana M, Merav AD, Robbins N.

Division of Infectious Diseases, Department of Internal Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th St, Bronx, NY 10467, USA.

J Infect. 2005 Jul 1; [Epub ahead of print]

ABSTRACT: Prosthetic valve endocarditis (PVE) due to Legionella micdadei was diagnosed in a man a year after valve replacement with a bovine xenograft. He did not have pneumonia. The microbiologic diagnosis was established after valvectomy, which was necessitated by failure of empiric antibiotics to eradicate the infection. The fastidious organism grew only on buffered charcoal yeast extract agar and was confirmed as L. micdadei by gene sequence analysis. We believe this to be the first culture-proven case of L. micdadei PVE reported in the literature.


In vitro activity of telithromycin against Gram-negative bacterial pathogens

Felmingham D, Farrell DJ.

G.R. Micro Ltd, 7-9 William Road, London NW1 3ER, UK.

J Infect. 2005 Jul 1; [Epub ahead of print]

ABSTRACT: OBJECTIVES: To investigate the in vitro activity of the ketolide anti-bacterial telithromycin against a range of commensal bacteria and common aerobic Gram-negative respiratory and non-respiratory pathogens. METHODS: Isolates were derived from both clinical material supplied by centres in various European countries and patients with community-acquired respiratory tract infections (RTIs) from centres worldwide as part of a longitudinal surveillance study. Telithromycin susceptibility testing was conducted using methods in accordance with Clinical and Laboratory Standards Institute (CLSI) guidelines and interpreted using CLSI breakpoints. RESULTS: Telithromycin displayed the highest activity against clinical isolates of Haemophilus spp., Neisseria spp., Bordetella pertussis, Legionella pneumophila and Moraxella catarrhalis, with low activity against a number of other bacterial species, including Acinetobacter spp., Enterobacteriaceae spp., Vibrio spp., Campylobacter jejuni, Aeromonas hydrophila, Plesiomonas shigelloides and Pseudomonas aeruginosa. CONCLUSIONS: Telithromycin provides coverage of key Gram-negative respiratory tract pathogens, but has minimal activity against Gram-negative non-respiratory pathogens and commensal bacteria. These data support the use of telithromycin as an alternative empirical therapy for community-acquired RTIs.


Antibacterial activities of gemifloxacin, levofloxacin, gatifloxacin, moxifloxacin and erythromycin against intracellular Legionella pneumophila and Legionella micdadei in human monocytes

Baltch AL, Bopp LH, Smith RP, Michelsen PB, Ritz WJ.

Infectious Disease Section, Stratton VA Medical Center, Albany, NY 12208, USA.

J Antimicrob Chemother. 2005 Jul;56(1):104-9.

ABSTRACT: OBJECTIVES: The antibacterial activity of a new fluoroquinolone, gemifloxacin, was tested against intracellular Legionella pneumophila and Legionella micdadei and was compared with the activities of levofloxacin, gatifloxacin, moxifloxacin and erythromycin. METHODS: For intracellular assays, bacteria were used to infect human monocyte-derived macrophages prepared from heparinized blood of healthy volunteers. Antibiotics were added following phagocytosis. Numbers of viable bacteria were determined at 0, 24, 48, 72 and 96 h. RESULTS: The intracellular antibacterial activity of gemifloxacin was concentration- and time-dependent. All of the quinolones had similar activities against L. pneumophila and L. micdadei at 10 x MIC, but there were minor differences: at 24 h moxifloxacin was significantly more active than the other quinolones against L. pneumophila, while gemifloxacin was more active against L. micdadei (P < 0.01). All of the quinolones were markedly more active than erythromycin (P < 0.01). The antibacterial effect of gemifloxacin against L. pneumophila following drug removal at 24 h persisted for 72 h at 20 x MIC but not at 10 x MIC, while for L. micdadei the antibacterial effect persisted for 24 h at 10 x MIC. CONCLUSIONS: All of the quinolones had similar activities against intracellular L. pneumophila and L. micdadei and were markedly more effective than erythromycin.


Efficacy of pazufloxacin mesilate in Legionnaires' disease: a case report and in vitro study of the isolate

Higa F, Shinzato T, Toyama M, Haranaga S, Furugen M, Tateyama M, Kawakami K, Saito A.

Department of Internal Medicine and Infectious Diseases, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, 903-0215, Japan.

J Infect Chemother. 2005 Jun;11(3):164-8.

ABSTRACT: We report here a case of culture-proven Legionnaires' disease successfully treated with intravenous injection of pazufloxacin mesilate (PZFX), a fluoroquinolone newly approved in Japan. The patient was a 51-year-old man hospitalized after a diagnosis of community-acquired pneumonia. Legionella pneumophila SG1 was isolated from the patient's bronchoalveolar lavage (BAL) fluid, and the soluble antigen of the bacterium was detected in the fluid as well. Subsequently, intravenous PZFX was administered for a week and proved markedly effective. An in vitro study confirmed that PZFX had excellent extracellular and intracellular activity against the isolate from the patient. This case suggests that PZFX is an option for treating Legionnaires' disease.



In vitro and intracellular activities of LBM415 (NVP PDF-713) against Legionella pneumophila

Edelstein PH, Hu B, Edelstein MA.

Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine and Clinical Microbiology Laboratory, Hospital of the University of Pennsylvania, Philadelphia, PA 19104-4283, USA.

Antimicrob Agents Chemother. 2005 Jun;49(6):2533-5.

ABSTRACT: LBM415 activity against extracellular and intracellular Legionella pneumophila was studied. The LBM415 MIC50 for 20 Legionella sp. strains was 4 microg/ml, versus 0.06, 0.25, and <or=0.03 microg/ml for azithromycin, erythromycin, and levofloxacin, respectively. LBM415 (0.5 and 16 microg/ml) reversibly prevented intracellular growth of two L. pneumophila strains and was less active than erythromycin.



Heterophile antibodies produce spuriously elevated concentrations of cardiac Troponin I in patients with Legionella pneumophila

Garcia-Mancebo ML, Agullo-Ortuno MT, Gimeno JR, Navarro-Martinez MD, Ruiz-Gomez J, Noguera-Velasco JA.

Servicio de Analisis Clinicos, Hospital Universitario "Virgen de la Arrixaca", Ctra. Madrid-Cartagena S/N, 30120 El Palmar (Murcia), Spain.

Clin Biochem. 2005 Jun;38(6):584-7.

ABSTRACT: We found an unusually high positive rate for cTnI in patients recently infected with Legionella pneumophila. The aim of this study was to examine the possible origin of increased cTnI levels and to test if it could be associated with the immune response to legionellosis. The cTnI was above the cut point in 46.7% of patients infected with legionellosis when measured with reagent lot number RF421A. A strong correlation between high cTnI measurements and positive serologic values for legionellosis was found. With a revised formulation of cTnI reagent, lot number RF421C, the positive rate decreased by over 10-fold to 3.3%. We conclude that the revised lot of cTnI reagent minimized interference by heterophilic antibodies produced in response to legionellosis.


Antibiotic susceptibilities of Legionella pneumophila strain Paris in THP-1 cells as determined by real-time PCR assay

Roch N, Maurin M.

CNRS UMR 5163, Universite Joseph Fourier, Faculte de Medecine, Batiment Jean Roget, 38700 La Tronche, France.

J Antimicrob Chemother. 2005 Jun;55(6):866-71.

ABSTRACT: OBJECTIVES: Legionella species are facultative intracellular bacteria. Evaluation of the activity of antibiotics against intracellular L. pneumophila is more predictive of their in vivo efficacy than MICs as determined in axenic medium. However, current methodologies are based on cfu count determination, and are tedious because of the slow growth of Legionella spp. We investigated antibiotic susceptibilities of L. pneumophila strain Paris in THP-1-derived macrophages, using a real-time PCR assay for evaluation of bacterial growth. METHODS: Intracellular activities of seven antibiotic compounds against two human isolates of L. pneumophila strain Paris were determined in THP-1-derived macrophages in vitro. Bacterial growth was evaluated using either cfu methodology or a real-time PCR protocol targeting the mip gene. RESULTS: Bacterial titres as determined using real-time PCR were well correlated with cfu counts. Antibiotic susceptibilities for the two L. pneumophila isolates tested were comparable when using either of the two techniques. MICs were also similar to those previously reported for other L. pneumophila serogroup 1 strains. In particular, rifampicin and the fluoroquinolones were the most active compounds, both in extracellular medium and in THP-1 cells. Real-time PCR, however, was much less laborious than the traditional cfu method. CONCLUSIONS: Real-time PCR is better adapted than cfu-based methods to evaluating the antibiotic susceptibilities of large series of Legionella strains to newer antibiotic compounds.


Efficacy and safety of telithromycin 800 mg once daily for 7 days in community-acquired pneumonia: an open-label, multicenter study

Fogarty CM, Patel TC, Dunbar LM, Leroy BP.

Spartanburg Medical Research, Spartanburg, South Carolina, USA.

BMC Infect Dis. 2005 May 31;5(1):43.

ABSTRACT: BACKGROUND: Community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality throughout the world. Telithromycin (a new ketolide) has shown good in vitro activity against the key causative pathogens of CAP, including S pneumoniae resistant to penicillin and/or macrolides. METHODS: The efficacy and safety of telithromycin 800 mg orally once daily for 7 days in the treatment of CAP were assessed in an open-label, multicenter study of 442 adults. RESULTS: Of 149 microbiologically evaluable patients, 57 (9 bacteremic) had Streptococcus pneumoniae. Of the 57 S pneumoniae pathogens isolated in these patients, 9 (2 bacteremic) were penicillin- or erythromycin-resistant; all 57 were susceptible to telithromycin and were eradicated. Other pathogens and their eradication rates were: Haemophilus influenzae (96%), Moraxella catarrhalis (100%), Staphylococcus aureus (80%), and Legionella spp. (100%). The overall bacteriologic eradication rate was 91.9%. Of the 357 clinically evaluable patients, clinical cure was achieved in 332 (93%). In the 430 patients evaluable for safety, the most common drug-related adverse events were diarrhea (8.1%) and nausea (5.8%). CONCLUSION: Telithromycin 800 mg once daily for 7 days is an effective and well-tolerated oral monotherapy and offers a new treatment option for CAP patients, including those with resistant S pneumoniae.


Comparative activity of quinolones, macrolides and ketolides against Legionella species using in vitro broth dilution and intracellular susceptibility testing

Stout JE, Sens K, Mietzner S, Obman A, Yu VL.

VA Pittsburgh Healthcare System, VA Medical Center, Infectious Disease Section, University Drive C, Pittsburgh, PA 15240, USA.

Int J Antimicrob Agents. 2005 Apr;25(4):302-7.

ABSTRACT: The comparative in vitro activity of quinolones (trovafloxacin, gemifloxacin, levofloxacin, ciprofloxacin, moxifloxacin and grepafloxacin), ketolides (ABT-773 and telithromycin) and macrolides (clarithromycin, azithromycin and erythromycin) were evaluated against Legionella pneumophila by broth dilution and an HL-60 intracellular model. The MIC90 of the quinolones, clarithromycin and ABT-773 were more than eight times lower than for erythromycin. Telithromycin, ABT-773 and azithromycin had significantly greater intracellular activity against L. pneumophila than erythromycin at 1xMIC and 8xMIC. The rank order of intracellular activity against L. pneumophila serogroup 1 was quinolones>ketolides>macrolides. Clinical trials to determine the clinical efficacy of ketolides for the treatment of Legionnaires' disease are warranted.


Empiric antibiotic coverage of atypical pathogens for community acquired pneumonia in hospitalized adults

Shefet D, Robenshtock E, Paul M, Leibovici L. Dept of Medicine E, Beilinson Campus, Rabin Medical Center, Petah-Tiqva, ISRAEL, 49100.

Cochrane Database Syst Rev. 2005 Apr 18;(2):CD004418.

ABSTRACT: BACKGROUND: Community acquired pneumonia (CAP) is caused by various pathogens, traditionally divided to 'typical' and 'atypical'. Initial antibiotic treatment of CAP is usually empirical, customarily covering both typical and atypical pathogens. To date, no sufficient evidence exists to support this broad coverage, while limiting coverage is bound to reduce toxicity, resistance and expense. OBJECTIVES: Assess the efficacy and need of adding antibiotic coverage for atypical pathogens in hospitalized patients with CAP, in terms of mortality and successful treatment. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2005) which includes the Acute Respiratory Infection Group's specialized register; MEDLINE (January 1966 to January Week 2 2005); and EMBASE (January 1980 to January Week 2 2005). SELECTION CRITERIA: Randomized trials of adult patients hospitalized due to CAP, comparing antibiotic regimens with atypical antibiotic coverage to a regimen without atypical antibiotic coverage. DATA COLLECTION AND ANALYSIS: Two reviewers independently appraised the quality of each trial and extracted the data from included trials. Relative risks (RR) with 95% confidence intervals (CI) were estimated, assuming an intention-to-treat (ITT) basis for the outcome measures. MAIN RESULTS: Twenty four trials were included, encompassing 5015 randomized patients. There was no difference in mortality between the atypical arm and the non-atypical arm (RR 1.13; 95% CI 0.82 to 1.54). The atypical arm showed an insignificant trend toward clinical success and a significant advantage to bacteriological eradication, which disappeared when evaluating methodologically high-quality studies alone. Clinical success for the atypical arm was significantly higher for Legionella pneumophilae (L. pneumophilae) and non-significantly lower for pneumococcal pneumonia. There was no significant difference between the groups in the frequency of (total) adverse events, or those requiring discontinuation of treatment. However, gastrointestinal events were more common in the non-atypical arm (RR 0.73, 95% CI 0.54 to 0.99). AUTHORS' CONCLUSIONS: No benefit of survival or clinical efficacy was shown to empirical atypical coverage in hospitalized patients with CAP. This conclusion relates mostly to the comparison of quinolone monotherapy to non-atypical monotherapy. Further trials, comparing beta-lactam (BL) or cephalosporin therapy to BL or cephalosporin combined with a macrolide in this population, using mortality as its primary outcome, should be performed.


Antimicrobial chemotherapy for legionnaires disease: levofloxacin versus macrolides

Blazquez Garrido RM, Espinosa Parra FJ, Alemany Frances L, Ramos Guevara RM, Sanchez-Nieto JM, Segovia Hernandez M, Serrano Martinez JA, Huerta FH.

Section of Infectious Diseases, Department of Microbiology, Hospital J. M. Morales Meseguer, Murcia, Spain.

Clin Infect Dis. 2005 Mar 15;40(6):800-6.

ABSTRACT: BACKGROUND: The community outbreak of legionnaires disease that occurred in Murcia, Spain, in July 2001--to our knowledge, the largest such outbreak ever reported--afforded an unusual opportunity to compare the clinical response of patients with Legionella pneumonia treated with levofloxacin with that of patients treated with macrolides and to determine the role of rifampicin combined with levofloxacin in treating severe legionellosis. METHODS: An observational, prospective, nonrandomized study was conducted involving 292 patients seen at our hospital (Hospital "J. M. Morales Meseguer"; Murcia, Spain) who received a diagnosis of Legionella pneumonia during the Murcia outbreak. To compare both antibiotic regimens (macrolides vs. levofloxacin), patients were stratified by the severity of pneumonia. Duration of fever, clinical outcome, complications, side effects, and length of hospital stay were recorded. To assess the potential effects of adjuvant therapy with rifampicin, 45 case patients treated with levofloxacin plus rifampicin were evaluated and compared with 45 control pairs who were treated with levofloxacin alone. RESULTS: With the exception of 2 patients who died, all patients were cured. There were no significant differences between treatment groups in clinical outcome for patients with mild-to-moderate pneumonia. Nevertheless, in patients with severe pneumonia, levofloxacin exerted superior activity; it was associated with fewer complications (3.4% of patients receiving levofloxacin experienced complications, compared with 27.2% of patients receiving macrolides; P=.02) and shorter mean hospital stays (5.5 vs. 11.3 days; P=.04). Addition of rifampicin to the treatment regimen for patients receiveing levofloxacin for severe pneumonia provides no additional benefit. CONCLUSIONS: Our findings strongly suggest that monotherapy with levofloxacin is a safe and effective treatment for legionnaires disease, including in patients with severe disease. In these patients, levofloxacin appears to be more effective than clarithromycin.


Clinical outcomes for hospitalized patients with Legionella pneumonia in the antigenuria era: the influence of levofloxacin therapy

Mykietiuk A, Carratala J, Fernandez-Sabe N, Dorca J, Verdaguer R, Manresa F, Gudiol F.

Infectious Disease Service, Institut d'Investigacio Biomedica de Bellvitge, Hospital Universitari de Bellvitge, University of Barcelona, Barcelona, Spain.

Clin Infect Dis. 2005 Mar 15;40(6):794-9.

ABSTRACT: BACKGROUND: Although the reduction in case-fatality rate recently observed among patients with Legionella pneumonia has been largely attributed to the progressive utilization of urine antigen testing, other factors, such as changes in empirical antibiotic therapy, may also have contributed. We have analyzed more-recent outcomes of Legionella pneumonia in an institution where urine antigen testing was reflexly performed in cases of community-acquired pneumonia without an etiological diagnosis. METHODS: From a prospective series of 1934 consecutive cases of community-acquired pneumonia in nonimmunocompromised adults, 139 cases of Legionella pneumophila pneumonia were selected for observational review. Legionella cases were analyzed for outcome with respect to antibiotic treatment, mortality, complications, length of stay, time to defervescence, and stability. RESULTS: The early case-fatality rate was 2.9% (4 of 139 patients), and the overall case-fatality rate was 5% (7 of 139 patients). One hundred twenty patients (86.3%) received an appropriate initial therapy, which included macrolides (i.e., erythromycin or clarithromycin) in 80 patients and levofloxacin in 40. Levofloxacin progressively replaced macrolides as the initial therapy during the study period. Compared with patients who received macrolides, patients who received levofloxacin had a faster time to defervescence (2.0 vs. 4.5 days; P<.001) and to clinical stability (3 vs. 5 days; P=.002). No differences were found regarding the development of complications (25% vs. 25%; P=.906) and case-fatality rate (2.5% vs. 5%; P=.518). The median length of hospital stay was 8 days in patients treated with levofloxacin and 10 days in those who received macrolides (P=.014). CONCLUSIONS: Legionella pneumonia is still associated with significant complications in hospitalized patients, but recent mortality is substantially lower than that found in earlier series. Levofloxacin may produce a faster clinical response than older macrolides, allowing for shorter hospital stay.


Treatment of Legionnaires' disease

Amsden GW.

Department of Adult and Pediatric Medicine, Section of Clinical Pharmacology and The Clinical Pharmacology Research Center, Bassett Healthcare, Cooperstown, NY 13326, USA.

Drugs. 2005;65(5):605-14.

ABSTRACT: Legionnaires' disease is pneumonia, usually caused by Legionella pneumophila, which can range in severity from mild to quite severe. While it is commonly acquired in the community, it can just as easily be acquired nosocomially from water sources that have not been appropriately decontaminated. While historically initial treatment was always with erythromycin, current case series and treatment recommendations suggest that outpatients receive immediate treatment with one of the following antibacterials: azithromycin, erythromycin, clarithromycin, telithromycin, doxycycline or an extended-spectrum fluoroquinolone. If the symptoms are severe enough to warrant hospitalisation then the patient should receive treatment with parenteral azithromycin or extended-spectrum fluoroquinolones followed by step-down to oral formulations to complete the regimens. While a shorter course of 7-10 days for more severe infections may be possible for intravenous/oral azithromycin, other antibacterials should be administered for a total of 10-21 days and started as soon as possible upon presentation to optimise outcomes.


Lower mortality among patients with community-acquired pneumonia treated with a macrolide plus a beta-lactam agent versus a beta-lactam agent alone

Garcia Vazquez E, Mensa J, Martinez JA, Marcos MA, Puig J, Ortega M, Torres A.

Infectious Diseases Department, Hospital Clinic Universitari, Barcelona, Spain.

Eur J Clin Microbiol Infect Dis. 2005 Mar;24(3):190-5.

ABSTRACT: A cohort of 1,391 patients with community-acquired pneumonia of unknown etiology, atypical pneumonia, Legionella pneumophila pneumonia, viral pneumonia, or pneumococcal pneumonia was studied according to a standard protocol to analyse whether the addition of a macrolide to beta-lactam empirical treatment decreases mortality rates. Patients admitted to the intensive care unit were excluded. Severity was assessed using the PORT score. An etiological diagnosis was achieved in 498 (35.8%) patients (292 infections due to Streptococcus pneumoniae). Treatment was chosen by the attending physician according to his/her own criteria: beta-lactam agent in 270 and beta-lactam agent plus a macrolide in 918 cases. The mortality rate was 13.3% in the group treated with a beta-lactam agent alone and 6.9% in the group treated with a beta-lactam agent plus a macrolide (p=0.001). The percentage of PORT-group V patients was 32.6% in the group treated with a beta-lactam agent alone compared to 25.7% in the group who received a beta-lactam agent plus a macrolide (p=0.02). After controlling for PORT score, the odds of fatal outcome was two times higher in patients treated with a beta-lactam agent alone than in those treated with a beta-lactam agent plus a macrolide (adjusted OR = 2, 95%CI 1.24-3.23). The results suggest that the addition of a macrolide to an initial beta-lactam-based antibiotic regimen is associated with lower mortality in patients with community-acquired pneumonia, independent of severity of infection, thus supporting the recommendation of a beta-lactam-agent plus a macrolide as empirical therapy. 



Effectiveness of {beta} lactam antibiotics compared with antibiotics active against atypical pathogens in non-severe community acquired pneumonia: meta-analysis

Mills GD, Oehley MR, Arrol B.

Respiratory and Infectious Diseases Department, Waikato Hospital, Private Bag 3200, Hamilton 2001, New Zealand.

BMJ. 2005 Feb 26;330(7489):456.

ABSTRACT: OBJECTIVE: To systematically compare beta lactam antibiotics with antibiotics active against atypical pathogens in the management of community acquired pneumonia. DATA SOURCES: Medline, Embase, Cochrane register of controlled trials, international conference proceedings, drug registration authorities, and pharmaceutical companies.Review methods Double blind randomised controlled monotherapy trials comparing beta lactam antibiotics with antibiotics active against atypical pathogens in adults with community acquired pneumonia. Primary outcome was failure to achieve clinical cure or improvement. RESULTS: 18 trials totalling 6749 participants were identified, with most patients having mild to moderate community acquired pneumonia. The summary relative risk for treatment failure in all cause community acquired pneumonia showed no advantage of antibiotics active against atypical pathogens over beta lactam antibiotics (0.97, 95% confidence interval 0.87 to 1.07). Subgroup analysis was undertaken in those with a specific diagnosis involving atypical pathogens. We found a significantly lower failure rate in patients with Legionella species who were treated with antibiotics active against atypical pathogens (0.40, 0.19 to 0.85). Equivalence was seen for Mycoplasma pneumoniae (0.60, 0.31 to 1.17) and Chlamydia pneumoniae (2.32, 0.67 to 8.03). CONCLUSIONS: Evidence is lacking that clinical outcomes are improved by using antibiotics active against atypical pathogens in all cause non-severe community acquired pneumonia. Although such antibiotics were superior in the management of patients later shown to have legionella related pneumonia, this pathogen was rarely responsible for pneumonia within the included trials. beta lactam agents should remain the antibiotics of initial choice in adults with non-severe community acquired pneumonia.


Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila in elderly patients with stroke (C-PEPS, M-PEPS, L-PEPS): a case-control study on the infectious burden of atypical respiratory pathogens in elderly patients with acute cerebrovascular disease

Ngeh J, Goodbourn C.

Department of Geriatric and Stroke Medicine, Warwick Hospital, Lakin Rd, Warwick CV34 5BW, UK.

Stroke. 2005 Feb;36(2):259-65.

ABSTRACT: BACKGROUND AND PURPOSE: Multiple studies have suggested an association between Chlamydia pneumoniae and Mycoplasma pneumoniae infection and cardiovascular disease. We investigated whether the risk of cerebrovascular disease is associated with Legionella pneumophila infection and the aggregate number/infectious burden of these atypical respiratory pathogens. METHODS: One hundred patients aged >65 years admitted with acute stroke or transient ischemic attack (TIA) and 87 control patients admitted concurrently with acute noncardiopulmonary, noninfective conditions were recruited prospectively. Using enzyme-linked immunosorbent assay (ELISA) kits, we previously reported the seroprevalences of C pneumoniae and M pneumoniae in these patients. We have now determined the seroprevalences of L pneumophila IgG and IgM in this cohort of patients using ELISA. RESULTS: The seroprevalences of L pneumophila IgG and IgM were 29% (n=91) and 12% (n=81) in the stroke/TIA group and 22% (n=86) and 10% (n=72) in the controls, respectively. Using logistic regression to adjust for age, sex, hypertension, smoking, diabetes, ischemic heart disease, and ischemic ECG, the odds ratios for stroke/TIA in relation to L pneumophila IgG and IgM were 1.52 (95% CI, 0.70 to 3.28; P=0.29) and 1.49 (95% CI, 0.45 to 4.90; P=0.51), respectively. The odds ratios in relation to IgG seropositivity for 1, 2, or 3 atypical respiratory pathogens after adjustment were 3.89 (95% CI, 1.13 to 13.33), 2.00 (95% CI, 0.64 to 6.21), and 6.67 (95% CI, 1.22 to 37.04), respectively (P=0.06). CONCLUSIONS: L pneumophila seropositivity is not significantly associated with stroke/TIA. However, the risk of stroke/TIA appears to be associated with the aggregate number of chronic infectious burden of atypical respiratory pathogens such as C pneumoniae, M pneumoniae, and L pneumophila.



Bronchoalveolar lavage findings in severe community-acquired pneumonia due to Legionella pneumophila serogroup 1

Trisolini R, Agli LL, Cancellieri A, Procaccio L, Candoli P, Alifano M, Patelli M.

Maggiore Hospital, Largo Nigrisoli 2, 40133 Bologna, Italy.

Respir Med. 2004 Dec;98(12):1222-6.

ABSTRACT: No specific data are available in the literature on the bronchoalveolar Lavage (BAL) findings of Legionella pneumophila pneumonia. We report on the cytological and immunophenotypical BAL data of three immunocompetent patients with severe community-acquired pneumonia due to L. pneumophila serogroup 1. METHODS: Retrospective chart review. The microbiologial diagnosis was obtained by BAL culture or/and urinary antigen assay. RESULTS: All patients presented with high-grade fever, bilateral chest infiltrates and severe respiratory failure requiring ventilatory support. The cytological BAL pattern at presentation showed in all patients the association of a marked neutrophilia with a variable but remarkable percentage of lymphoblasts. Increased levels of activated T-Lymphocytes (both HLA-DR + and CD25 + cells) and, in 2 out of 3 patients, of T-cells bearing the gamma/delta T-cell receptor were the main immunophenotypical findings on flow cytometric analysis. CONCLUSIONS: We suggest that the association of lymphoblasts with a marked neutrophilia in BAL fluid of patients with a clinical-radiological setting compatible with acute pneumonia should suggest L. pneumophila as a possible etiologic agent.


A case of Legionnaires' disease with extensive concurrent deep vein thrombosis

Samman YS, Abdelaal MA, Wali SO, Almalki AH, Abdelaziz MM.

Department of Medicine, King Khalid National Guard Hospital , Jeddah , Saudi Arabia .

Scand J Infect Dis. 2004;36(10):765-7

ABSTRACT: A previously healthy 37-y-old male presented with community-acquired pneumonia and extensive upper limb deep vein thrombosis. The diagnosis of Legionella pneumonia was made based on a positive direct immunofluorescence of the bronchial wash. An extensive investigation for hypercoagulable states was negative. The possible association between Legionella infection and deep vein thrombosis is highlighted.


In vitro activity of thiamphenicol, erythromycin and fluoroquinolones against Legionella pneumophila

Bonfiglio G, Lanzafame A, Santini L, Mattina R.

J Chemother. 2004 Oct;16(5):502-3.




Efficacy of telithromycin in community-acquired pneumonia caused by Legionella pneumophila

Carbon C, Nusrat R.

Department of Antiinfectives and Pulmonary Clinical Development, Aventis, Mailstop BX2-312A, 200 Crossing Boulevard, 08807, Bridgewater, NJ, USA.

Eur J Clin Microbiol Infect Dis. 2004 Aug;23(8):650-2.



Gemifloxacin: a new fluoroquinolone approved for treatment of respiratory infections

Yoo BK, Triller DM, Yong CS, Lodise TP

College of Pharmacy, Yeungnam University, Dae-dong Kyungsan-si, South Korea.

Ann Pharmacother. 2004 Jul-Aug;38(7-8):1226-35.

ABSTRACT: OBJECTIVE: To evaluate the microbiology, pharmacokinetic parameters, drug interactions, and results of the available clinical trials of gemifloxacin for the treatment of community-acquired pneumonia (CAP) and acute exacerbation of chronic bronchitis (AECB). DATA SOURCES: MEDLINE (1966-September 2003) was searched for primary and review articles. Data from the manufacturer were also included. Key words included adverse effects, clinical trials, drug interactions, gemifloxacin, and pharmacokinetic parameters. STUDY SELECTION AND DATA EXTRACTION: All articles and product labeling concerning gemifloxacin, a fluoroquinolone antibiotic recently approved by the Food and Drug Administration for treatment of CAP and AECB, were included for review. DATA SYNTHESIS: Compared with currently available fluoroquinolones, gemifloxacin demonstrated improved in vitro activity against Streptococcus pneumoniae (minimum inhibitory concentration for 90% eradication 0.03 microg/mL) and similar activity against gram-negative respiratory pathogens (Haemophilus influenzae, Moraxella catarrhalis) and atypical pathogens such as Chlamydia pneumoniae, Legionella pneumophila, and Mycoplasma pneumoniae. Gemifloxacin, consistent with other available fluoroquinolones, has insufficient activity against methicillin-resistant Staphylococcus aureus to allow clinical use for such infections. Gemifloxacin has adequate bioavailability and a favorable drug interaction profile. Gemifloxacin was comparable to commonly employed nonfluoroquinolone regimens for treatment of CAP and AECB, although the studies were designed to demonstrate equivalence. Gemifloxacin once daily for 5-7 days was well tolerated in controlled and uncontrolled clinical studies. Available clinical data, however, are insufficient to draw clinical or toxicologic distinctions between gemifloxacin and other fluoroquinolones. CONCLUSIONS: Gemifloxacin may be a suitable choice for empiric treatment of CAP or AECB. However, due to the significant history of fluoroquinolone-induced hepatic failure and dermatologic complications, the use of this drug should be closely monitored.




The antimicrobial activity of lactoferrin: current status and perspectives

Orsi N.

Department of Public Health Sciences, University of Rome La Sapienza , Italy .

Biometals. 2004 Jun;17(3):189-96.

ABSTRACT: Lactoferrin (Lf) is a multifunctional iron glycoprotein which is known to exert a broad-spectrum primary defense activity against bacteria, fungi, protozoa and viruses. Its iron sequestering property is at the basis of the bacteriostatic effect, which can be counteracted by bacterial pathogens by two mechanisms: the production of siderophores which bind ferric ion with high affinity and transport it into cells, or the expression of specific receptors capable of removing the iron directly from lactoferrin at the bacterial surface. A particular aspect of the problem of iron supply occurs in bacteria (e.g. Legionella) which behave as intracellular pathogens, multiplying in professional and non professional macrophages of the host. Besides this bacteriostatic action, Lf can show a direct bactericidal activity due to its binding to the lipid A part of bacterial LPS, with an associated increase in membrane permeability. This action is due to lactoferricin (Lfc), a peptide obtained from Lf by enzymatic cleavage, which is active not only against bacteria, but even against fungi, protozoa and viruses. Additional antibacterial activities of Lf have also been described. They concern specific effects on the biofilm development, the bacterial adhesion and colonization, the intracellular invasion, the apoptosis of infected cells and the bactericidal activity of PMN. The antifungal activity of Lf and Lfc has been mainly studied towards Candida, with direct action on Candida cell membranes. Even the sensitivity of the genus tricophyton has been studied, indicating a potential usefulness of this molecule. Among protozoa, Toxoplasma gondii is sensitive to Lf, both in vitro and in vivo tests, while Trichomonads can use lactoferrin for iron requirements. As to the antiviral activity, it is exerted against several enveloped and naked viruses, with an inhibition which takes place in the early phases of viral invection, as a consequence of binding to the viral particle or to the cell receptors for virus. The antiviral activity of Lf has also been demonstrated in in vivo model invections and proposed for a selective delivery of antiviral drugs. The new perspectives in the studies on the antimicrobial activity of Lf appear to be linked to its potential prophylactic and therapeutical use in a considerable spectrum of medical conditions, taking advantage of the availability of the recombinant human Lf. But the historical evolution of our knowledge on Lf indicates that its antimicrobial activity must be considered in a general picture of all the biological properties of this multifunctional protein.


Levofloxacin efficacy in the treatment of community-acquired legionellosis

Yu VL, Greenberg RN, Zadeikis N, Stout JE, Khashab MM, Olson WH, Tennenberg AM.

VAMC and University of Pittsburgh , Pittsburgh , PA , USA .

Chest. 2004 Jun;125(6):2135-9.

ABSTRACT: BACKGROUND: Although fluoroquinolones possess excellent in vitro activity against Legionella, few large-scale clinical trials have examined their efficacy in the treatment of Legionnaires disease. Even fewer studies have applied rigorous criteria for diagnosis of community-acquired Legionnaires disease, including culture of respiratory secretions on selective media. METHODS: Data from six clinical trials encompassing 1,997 total patients have been analyzed to determine the efficacy of levofloxacin (500 mg qd or 750 mg qd) in treating patients with community-acquired pneumonia (CAP) due to Legionella. RESULTS: Of the 1,997 total patients with CAP from the clinical trials, 75 patients had infection with a Legionella species. Demographics showed a large portion of these patients were < 55 years of age and nonsmokers. More than 90% of mild-to-moderate and severe cases of Legionella infection resolved clinically at the posttherapy visit, 2 to 14 days after treatment termination. No deaths were reported for any patient with Legionnaires disease treated with levofloxacin during the studies. CONCLUSIONS: Levofloxacin was efficacious at both 500 mg for 7 to 14 days and 750 mg for 5 days. Legionnaires disease is not associated only with smokers, the elderly, and the immunosuppressed, but also has the potential to affect a broader demographic range of the general population than previously thought.


Legionella in two splenectomized patients. Coincidence or causal relationship?

Gorelik O, Lazarovich Z, Boldur I, Almoznino-Sarafian D, Alon I, Modai D, Cohen N.

Dept. of Internal Medicine "F", Assaf Harofeh Medical Center , Affiliated with Sackler Faculty of Medicine, Tel Aviv University , Zerifin 70300 , Israel .

Infection. 2004 Jun;32(3):179-81.

ABSTRACT: We describe two splenectomized patients admitted with pneumonia. The course in one was complicated by overwhelming multiorgan failure when the only indicative laboratory result was seropositivity for Legionella hackeliae and Legionella longbeachae. He was initially treated with ceftriaxone and roxithromycin, followed by levofloxacin as well as intensive supportive treatment, and survived. The second patient was seroreactive for Legionella micdadei. In some cases of pneumonia in splenectomized patients tentatively considered to be caused by Streptococcus pneumoniae, the causative agent might have, in fact, been Legionella. We suggest that splenectomy be considered a possible predisposing factor for Legionella pneumonia. Since prompt diagnosis of Legionella infection, especially the non- pneumophila species, is extremely difficult, alertness to this diagnostic option and early empirical initiation of appropriate aggressive antibiotic treatment may be of critical importance.



Reactive knee and ankle joint arthritis: abnormal manifestation of Legionella pneumophila

Andereya S, Schneider U, Siebert CH, Wirtz DC.

Department of Orthopaedics, Aachen University Hospital, Pauwelsstrasse 30, 52074, Aachen, Germany,

Rheumatol Int. 2004 May;24(3):182-4.

ABSTRACT: This case report demonstrates that active legionellosis is not always characterised by pulmonary symptoms and specific radiomorphological findings. Whereas the initial clinical presentation, as described in the literature, includes fever, cough, expectoration, extrapulmonary organ changes or typical laboratory findings, atypical manifestations such as reactive arthritis must be considered.  


Gemifloxacin: a new fluoroquinolone

Blondeau JM, Missaghi B.

Department of Microbiology, Royal University Hospital, Saskatoon, Saschatchewan, Canada.
Expert Opin Pharmacother. 2004 May;5(5):1117-1152.

ABSTRACT: Gemifloxacin is a dual targeted fluoroquinolone with potent in vitro activity against Gram-positive, -negative and atypical human pathogens - pathogens considered to be important causes of community-acquired respiratory tract infections. Gemifloxacin demonstrates impressive minimal inhibitory concentrations (MIC 90 ) values against clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniae and Legionella spp., with MIC 90 values reported to be 0.016 - 0.06, < 0.0008 - 0.06, 0.008 - 0.3, 0.25, 0.125 and 0.016 - 0.07 microg/ml, respectively. Gemifloxacin is also active in vitro against a broad range of Gram-negative bacilli with MIC 90 values against the Enterobacteriaceae in the range of 0.016 to > 16 microg/ml ( Escherichia coli and Providencia stuartii, respectively), with the majority of the genus having MIC 90 drug concentrations < 0.5 microg/ml. The in vitro activity of gemifloxacin against anaerobic organisms is variable. The MIC values for gemifloxacin are not affected by beta-lactamase production nor by penicillin or macrolide resistance in S. pneumoniae. Gemifloxacin is approved by the FDA to be clinically efficacious against multi-drug resistant S. pneumoniae. The pharmacokinetics of gemifloxacin are such that the drug can be administered orally once-daily to yield or achieve sustainable drug concentrations exceeding the MIC values of clinically important organisms. Gemifloxacin has been shown to target both DNA gyrase (preferred target) and topoisomerase IV (secondary target) - enzymes critical for DNA replication and organism survival - against clinical isolates of S. pneumoniae. This dual targeting activity is thought to be important for reducing the likelihood for selecting for quinolone resistance. Gemifloxacin has been investigated and approved for therapy in patients with community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis. In one study, more patients receiving gemifloxacin compared to clarithromycin remained free of exacerbations for longer periods of time (p < 0.016) and gemifloxacin had a shorter time to eradication of H. influenzae than did clarithromycin (p < 0.02). From efficacy studies, gemifloxacin was found to have an adverse profile that was comparable with other compounds. The most frequent side effects were diarrhoea, abdominal pain and headache. Gemifloxacin is a welcomed addition to currently available agents for the treatment of community-acquired lower respiratory tract infections. Other potential indications appear to be within the spectrum of this compound.  



Pneumonia and Osteomyelitis Due to Legionella longbeachae in a Woman with Systemic Lupus Erythematosus

McClelland MR, Vaszar LT, Kagawa FT.

Department of Medicine and 2Division of Pulmonary and Critical Care Medicine, Stanford University, San Jose, CA, 95128, USA.

Clin Infect Dis. 2004 May 15;38(10):E102-6.

ABSTRACT: A patient with risk factors of systemic lupus erythematosus, corticosteroid use, and malignancy received a diagnosis of concomitant pneumonia and osteomyelitis caused by Legionella longbeachae. In this report, the first description of Legionella osteomyelitis, previous cases of extrapulmonary Legionella infection are detailed.  



Reversible corpus callosum lesion in legionnaires' disease

Morgan JC, Cavaliere R, Juel VC.

Department of Neurology, Medical College of Georgia, Augusta, Georgia, USA.

J Neurol Neurosurg Psychiatry. 2004 Apr;75(4):651-4.

ABSTRACT: Legionnaires' disease is often associated with neurological findings. Despite such findings, computed tomography and neuropathological investigations are typically normal. This report describes a reversible lesion of the corpus callosum identified on magnetic resonance imaging (MRI) in a patient with legionnaires' disease. MRI may show previously undocumented neuropathology in acute legionnaires' disease. Legionella pneumophila infection should be included in the differential diagnosis of conditions associated with reversible lesions of the corpus callosum.



Legionella micdadei infection presenting as severe secretory diarrhea and a solitary pulmonary mass

Medarov BI, Siddiqui AK, Mughal T, Moshiyakhov M, Rossoff LJ.

Department of Pulmonary and Critical Care Medicine, Long Island Jewish Medical Center, New Hyde Park, New York 11040, USA.

Clin Infect Dis. 2004 Apr 1;38(7):e63-5.

ABSTRACT: Sixty percent of infections with non-pneumophila species of Legionella are caused by Legionella micdadei. Although diarrhea is a common symptom of legionellosis, including that due to L. micdadei infection, severe, life-threatening diarrhea is rare. We describe a patient with profound secretory diarrhea (secretion rate, up to 8 L/day) that was secondary to culture-proven L. micdadei pneumonia. In addition, a 3-cm pulmonary nodule was detected, which completely resolved after proper treatment for Legionella infection. Resolving pulmonary nodules have been previously reported in association with treatment of L. micdadei infections.


Acute renal failure associated with Legionella pneumonia and acute cholecystitis

Fung AS, Leikis MJ, McMahon LP.

Department of Nephrology, Western Hospital, Victoria, Australia.

Nephrology (Carlton). 2004 Apr;9(2):105-8.

ABSTRACT: BACKGROUND AND AIMS: Acute cholecystitis in critically ill patients has a high morbidity and mortality. We observed a number of patients presenting with Legionella pneumonia and acute renal failure who subsequently developed acute cholecystitis. There has previously been no reported association between Legionella pneumonia, renal failure and cholecystitis, prompting this examination of the cases and review of the available literature. METHODS: The Western Hospital patient record discharge codes (DRG) from 1993 to 2001 were searched retrospectively for all cases of Legionella pneumonia or acute renal failure requiring dialysis (ARF) at presentation or during their period of hospitalization. Acute cholecystitis was then included as a cross-search and results analysed. RESULTS: Twenty-six cases of isolated Legionella pneumonia and 112 of ARF were identified with a further 10 having both conditions simultaneously. Of these 10 cases, three were identified as also having acute cholecystitis. The combination of Legionella pneumonia and ARF was associated with an increased risk of acute cholecystitis (P = 0.002) whereas neither condition in isolation demonstrated this association. CONCLUSIONS: Patients with Legionella pneumonia can become critically ill with multiple complications including acute renal failure requiring dialysis. In this setting, they may have an increased risk of developing acute cholecystitis, which clinically can be difficult to ascertain. Diagnosis requires a high index of suspicion and vigilance.



Efficacy of 750-mg, 5-day levofloxacin in the treatment of community-acquired pneumonia caused by atypical pathogens

Dunbar LM, Khashab MM, Kahn JB, Zadeikis N, Xiang JX, Tennenberg AM.

Louisiana State University Medical Center, New Orleans, LA, USA.

Curr Med Res Opin. 2004 Apr;20(4):555-63.

ABSTRACT: BACKGROUND: Current recommended durations for treatment of atypical community-acquired pneumonia (CAP) range from 10 to 21 days. However, antibiotics such as the fluoroquinolones may allow for effective, short-course regimens. OBJECTIVE: This study evaluated the efficacy of 750 mg levofloxacin for 5 days compared to a 500-mg, 10-day levofloxacin regimen for the treatment of atypical CAP. METHODS: A randomized, active-controlled, double-blind, multicenter study was conducted within the United States. Of the 528 patients enrolled in the study, 149 were diagnosed with CAP due to Legionella pneumophila, Chlamydia pneumoniae, or Mycoplasma pneumoniae. Patients' baseline symptoms were re-evaluated on Day 3 of therapy. Clinical efficacy and resolution of CAP symptoms were evaluated at the posttherapy visit (7-14 days after the last dose of active drug). RESULTS: This report represents a subgroup analysis of a previous clinical study. Among the 123 clinically evaluable patients diagnosed with atypical CAP (26 patients were unevaluable), the clinical success rates were 95.5% (63 of 66 patients) for the 750-mg group and 96.5% (55 of 57 patients) for the 500-mg group (95% CI for success rate of the 500-mg group minus that of the 750-mg group, -6.8 to 8.8). At the poststudy evaluation (31-38 days after treatment began), relapse occurred in </= 2% of patients in either treatment group. Among patients diagnosed with atypical CAP, the 750-mg therapy resulted in more rapid symptom resolution, with a significantly greater proportion of patients experiencing resolution of fever by Day 3 of therapy (p = 0.031). CONCLUSION: The 750-mg, 5-day course of levofloxacin was at least as effective as the 500-mg, 10-day regimen for atypical CAP. Additionally, the 750-mg, short-course levofloxacin therapy may reduce total antimicrobial drug usage and more rapidly relieve pneumonia symptoms.



Acute renal failure associated with legionellosis

Brewster UC.

Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, LMP 2071, 333 Cedar Street, New Haven, CT 06520-8029, USA.

Ann Intern Med. 2004 Mar 2;140(5):406-7.




Legionella pneumophila serogroup 4 isolated from joint tissue

Linscott AJ, Poulter MD, Ward K, Bruckner DA.

Department of Pathology and Laboratory Medicine, University of California , Los Angeles Medical Center , Los Angeles , California , USA .

J Clin Microbiol. 2004 Mar;42(3):1365-6.

ABSTRACT: We report the isolation of Legionella pneumophila serogroup 4 from synovial tissue obtained from an 80-year-old female with chronic swelling of her right metacarpophalangeal joint. Synovial tissue infections caused by L. pneumophila are rare. Interestingly, this isolate was recovered from chocolate agar after 5 days of incubation.


Causes and factors associated with early failure in hospitalized patients with community-acquired pneumonia

Roson B, Carratala J, Fernandez-Sabe N, Tubau F, Manresa F, Gudiol F.

Infectious Disease Service, Hospital Universitari de Bellvitge, University of Barcelona, L'Hospitalet, Barcelona, Spain.

Arch Intern Med. 2004 Mar 8;164(5):502-8.

ABSTRACT: BACKGROUND: Early failure is a matter of great concern in the treatment of community-acquired pneumonia. However, information on its causes and risk factors is lacking. METHODS: Observational analysis of a prospective series of 1383 nonimmunosuppressed hospitalized adults with community-acquired pneumonia. Early failure was defined as lack of response or worsening of clinical or radiologic status at 48 to 72 hours requiring changes in antibiotic therapy or invasive procedures. Concordance of antimicrobial therapy was examined for cases with an etiologic diagnosis. RESULTS: At 48 to 72 hours, 238 patients (18%) remained febrile, but most of them responded without further changes in antibiotic therapy. Eighty-one patients (6%) had early failure. The main causes of early failure were progressive pneumonia (n = 54), pleural empyema (n = 18), lack of response (n = 13), and uncontrolled sepsis (n = 9). Independent factors associated with early failure were older age (>65 years) (odds ratio [OR], 0.35), multilobar pneumonia (OR, 1.81), Pneumonia Severity Index score greater than 90 (OR, 2.75), Legionella pneumonia (OR, 2.71), gram-negative pneumonia (OR, 4.34), and discordant antimicrobial therapy (OR, 2.51). Compared with treatment responders, early failures had significantly higher rates of complications (58% vs 24%) and overall mortality (27% vs 4%) (P<.001 for both). CONCLUSIONS: Early failure is infrequent but is associated with high morbidity and mortality rates. Its detection and management require careful clinical assessment. Most cases occur because of inadequate host-pathogen responses. Discordant therapy is a less frequent cause of failure, which may be preventable by rational application of the current antibiotic guidelines.


Abnormal radiological findings and a decreased carbon monoxide transfer factor can persist long after the acute phase of Legionella pneumophila pneumonia

Jonkers RE, Lettinga KD, Pels Rijcken TH, Prins JM, Roos CM, van Delden OM, Verbon A, Bresser P, Jansen HM.

Department of Pulmonology, Division of Infectious Diseases, Tropical Medicine, and AIDS, Amsterdam, The Netherlands.

Clin Infect Dis. 2004 Mar 1;38(5):605-11.

ABSTRACT: Pulmonary abnormalities may persist long after the acute phase of legionnaires disease (LD). In a cohort of 122 survivors of an outbreak of LD, 57% were still experiencing an increased number of symptoms associated with dyspnea at a mean of 16 months after recovery from acute-phase LD. For 86 of these patients, additional evaluation involving high-resolution computed tomography (HRCT) of the lung revealed pulmonary abnormalities in 21 (24%); abnormal HRCT findings generally presented as discrete and multiple radiodensities. Residual pulmonary abnormalities were associated with a mean reduction of 20% in the gas transport capacity of the lung. This latter sign could not be used to explain the increased symptoms of dyspnea reported by patients. Receipt of mechanical ventilation during the acute phase of LD, delayed initiation of adequate antibiotic therapy, and chronic obstructive pulmonary disease were identified as risk factors for the persistence of lung abnormalities.


Légionellose chez une patiente sous infliximab [Legionellosis in patient treated with infliximab]

Albert C, Vandenbos F, Brocq O, Carles D, Euller-Ziegler L.

Service de rhumatologie, hôpital de l'Archet-I, CHU de Nice, 151, route Saint-Antoine-de-Ginestière, BP 3079, 06202, Nice cedex 3, France.

Rev Med Interne. 2004 Feb;25(2):167-8.




Ciprofloxacin-induced acute interstitial pneumonitis
Steiger D, Bubendorf L, Oberholzer M, Tamm M, Leuppi JD.
Dept of Internal Medicine, University Hospital, Basel, Switzerland.
Eur Respir J. 2004 Jan;23(1):172-4.

ABSTRACT: The current authors present the case of a 68-yr-old female patient who developed severe respiratory failure after medication with ciprofloxacin for acute urinary tract infection. A chronic subdural haematoma was surgical evacuated. Postoperatively, an acute urinary tract infection was treated with ciprofloxacin. Six days later, C-reactive protein was rising and the patient was suffering from intermittent high fever, dyspnoea and severe hypoxaemia. The high-resolution-computed tomography (HRCT) showed an interstitial lung disease in the anterior upper lobe on the left side as well as in the lingula. Assuming a bacterial infection amoxyl/clavulanic acid was started which did not improve the clinical symptoms. Bronchoalveolar lavage revealed a marked lymphocytosis (87%). Analysis for typical bacterial infections, Tuberculosis, Mycoplasma, Chlamydia and Legionella spp. were all negative. Another HRCT scan was made because of worsening of symptoms and this showed rapidly progressive infiltrates in most lobes. An open lingular biopsy showed an interstitial lymphoplasmocytotic infiltrate with some eosinophilic granulocytes and a few scattered giant cell granulomas, consistent with hypersensitivity pneumonitis. The patient's symptoms rapidly improved with systemic corticosteroid therapy and another HRCT scan revealed complete remission of pulmonary infiltrates. Ciprofloxacin can induce interstitial pneumonitis with acute respiratory failure. This is an important fact considering that ciprofloxacin is a widely used antibiotic agent in treatment of urinary tract infection.

  Legionella pneumonia: infection during immunosuppressive therapy for idiopathic pulmonary hemosiderosis
Watson AM, Boyce TG, Wylam ME.

Department of Pediatrics and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester MN.

Pediatr Infect Dis J. 2004 Jan;23(1):82-4.

ABSTRACT: We report a case of Legionella pneumonia in a 10-year-old girl with idiopathic pulmonary hemosiderosis who was chronically immunosuppressed and had exposure to a hot tub. Prompt diagnosis with bronchoalveolar lavage and subsequent antimicrobial therapy resulted in full recovery. Legionellosis should be included in the differential diagnosis of the immunosuppressed child with respiratory illness. High risk patients should avoid exposure to hot tubs.



Cerebellar involvement in legionellosis
Shelburne SA, Kielhofner MA, Tiwari PS.
Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, St. Luke's Episcopal Hospital, Houston, TX 77030, USA.

South Med J. 2004 Jan;97(1):61-4.

ABSTRACT: The involvement of the cerebellum in Legionnaires' disease has been noted in occasional case reports, but there have been no reviews on this subject to date. We report a previously healthy patient who contracted Legionella pneumonia and developed profound cerebellar dysfunction during his illness. He was treated with antibiotics with improvement of his pneumonia, but his cerebellar symptoms persisted. We review 29 case reports of cerebellar dysfunction in Legionnaires' disease and summarize the clinical course, cultures, cerebrospinal fluid analyses, and neuroimaging. Finally, possible methods of pathogenicity are discussed including data regarding direct bacterial invasion, toxin production, and immune-mediated mechanisms.

Legionella and Q fever community acquired pneumonia in children

Scola BL, Maltezou H.

Unite des Rickettsies, CNRS UMR 6020, Marseille, France.

Paediatr Respir Rev. 2004;5 Suppl A:S171-7.




Azithromycin in the treatment of Legionella pneumonia requiring hospitalization
Plouffe JF, Breiman RF, Fields BS, Herbert M, Inverso J, Knirsch C, Kolokathis A, Marrie TJ, Nicolle L, Schwartz DB
Ohio State University, Columbus, Ohio, USA.

Clin Infect Dis. 2003 Dec 1;37(11):1475-80.

ABSTRACT: Azithromycin is highly active against Legionella pneumophila and has been shown to be efficacious in animal models and in clinical studies of patients with legionnaires disease. This open, prospective, multicenter trial evaluated azithromycin for the treatment of legionnaires disease. Twenty-five hospitalized patients with community-acquired pneumonia and a positive result of a L. pneumophila serogroup 1 urinary antigen assay received monotherapy with intravenous azithromycin (500 mg/day) for 2-7 days, followed by oral azithromycin (1500 mg administered over the course of 3 or 5 days). The mean total duration of intravenous plus oral therapy was 7.92 days. The overall cure rate among clinically evaluable patients was 95% (20 of 21 patients) at 10-14 days after therapy and 96% (22 of 23 patients) at 4-6 weeks after therapy. The results of this study support previously reported data demonstrating that azithromycin is both safe and efficacious for the treatment of hospitalized patients with legionnaires disease.


Current issues in the management of bacterial respiratory tract disease: the challenge of antibacterial resistance

Dunbar LM.

Louisiana State University Medical Center, New Orleans, Louisiana 70112, USA.

Am J Med Sci. 2003 Dec;326(6):360-8.

ABSTRACT: The worldwide burden of respiratory tract disease is enormous. Resistance to penicillins, macrolides, and cephalosporins is now detected among the leading bacterial pathogens that cause respiratory tract infections (RTIs)-Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The increasing role of atypical/intracellular pathogens (eg, Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella pneumophila) in RTIs, as well as their increase in antibiotic resistance prevalence, continues to be of great concern. More recently introduced treatment options for RTIs include the newer respiratory fluoroquinolones, along with the macrolides and azalides. Although these agents demonstrate good activity against common respiratory pathogens, reduced susceptibility to these agents has been reported. The ketolides are recently developed antibacterial agents with targeted-spectrum activity against common respiratory tract pathogens, including atypical/intracellular pathogens, and a low potential for inducing resistance. These promising new drugs have shown in vitro and in vivo efficacy in the treatment of community-acquired RTIs, such as community-acquired pneumonia, acute exacerbations of chronic bronchitis, and acute bacterial maxillary sinusitis.


In vitro and in vivo activity of olamufloxacin (HSR-903) against Legionella spp
Higa F, Arakaki N, Tateyama M, Koide M, Shinzato T, Kawakami K, Saito A.
First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan.

J Antimicrob Chemother. 2003 Dec;52(6):920-4.

ABSTRACT: The activity of the fluoroquinolone olamufloxacin (HSR-903) against Legionella spp. was studied in vitro and in vivo. The olamufloxacin MIC at which 50% of isolates are inhibited (MIC50) for 81 different Legionella spp. strains (59 type strains and 22 clinical isolates) was 0.008 mg/L, which was identical to sparfloxacin, whereas the MIC50s for erythromycin, levofloxacin and ciprofloxacin were 0.25, 0.032 and 0.032 mg/L, respectively. Olamufloxacin and sparfloxacin (at 0.008 mg/L) inhibited intracellular growth and subsequent cytotoxicity of L. pneumophila 80-045 in J774.1 macrophages, whereas levofloxacin and ciprofloxacin did not, at the same concentration. When olamufloxacin was given to the infected guinea pigs orally (5 mg/kg of body weight), peak levels in the lung were 3.02 mg/kg at 2 h post-administration, with a half-life of 3.41 h and an AUC0-12 of 12.31 mg.h/kg. The 2 day post-infection bacterial burden of the lung in the animals treated with olamufloxacin (5 and 1.25 mg/kg given orally twice a day) was much lower than in those treated with levofloxacin (same dose as olamufloxacin) or erythromycin (10 mg/kg given orally twice a day). When treated with olamufloxacin (5 mg/kg given orally twice a day) for 7 days, 11 of 12 L. pneumophila-infected guinea pigs survived for 14 days post-infection, as did all 12 guinea pigs treated with levofloxacin (5 mg/kg given orally twice a day) for 7 days. In contrast, only two of 12 animals treated with erythromycin survived and 10 of 11 died in the physiological saline group. Olamufloxacin was as effective as levofloxacin in a guinea pig model of Legionnaires' disease. These data warrant further study of whether olamufloxacin is an option for the treatment of Legionella infections.


Treatment and outcome of 104 hospitalized patients with legionnaires' disease

Howden BP, Stuart RL, Tallis G, Bailey M, Johnson PD.

Department of Microbiology, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia.

Intern Med J. 2003 Nov;33(11):484-8.

ABSTRACT: BACKGROUND: Large outbreaks of Legionella pneumonia are rare, but when they occur provide an opportunity to assess predictors of mortality and efficacy of drug therapy. Although erythromycin has been the treatment of choice for many years, newer antimicrobials with increased activity against Legionella are available. A large outbreak of legionnaires' disease associated with the Melbourne Aquarium occurred in April 2000. AIM: To describe the patterns and impact of Legionella therapy, and predictors of outcome in a large group of hospitalized patients with legionnaires' disease. METHODS: A 6-month retrospective audit of hospitalized patients with proven legionnaires' disease around the time of the Melbourne Aquarium outbreak was conducted. Statistical analysis was performed using SAS version 8.0 (SAS Institute Inc., NC, USA). RESULTS: Data were obtained on 104 patients (71 aquarium related, 33 not related). There were six deaths (mortality rate 5.8%), three of which were attributable directly to progressive legionnaires' disease. The major predictors of death were pre-existing cardiac failure (P = 0.0035) and renal disease (P = 0.026). Erythro-mycin is still the most commonly used antibiotic (80% received i.v. erythromycin) with clinicians prescribing more than one active Legionella drug in the majority of cases (76%). Choice of initial antibiotic therapy did not statistically affect outcome as measured by death, length of hospital stay or time to defervescence, although there was a trend towards improved survival with i.v. erythromycin (P = 0.063). Intravenous erythromycin was associated with a 19% rate of phlebitis, whereas side-effects from other antibiotics were uncommon. CONCLUSION: The most commonly used Legionella therapy in Australia remains erythromycin. This continues to be an effective agent, however, side-effects are common.


Sinoatrial block complicating legionnaire's disease

Medarov B, Tongia S, Rossoff L.

Division of Pulmonary and Critical Care Medicine, Long Island Jewish Medical Centre, The Long Island Campus of the Albert, 410 Lakeville Road, Suite 203, New Hyde Park, NY 11040, USA.

Postgrad Med J. 2003 Nov;79(937):657-9.

ABSTRACT: A 59 year old woman presented with acute onset of fever, chills, diaphoresis, vague chest discomfort, and was found to be hypotensive and tachypnoeic. An electrocardiogram demonstrated sinoatrial block with a junctional rhythm between 50 and 80 beats/min. All cultures were negative and imaging studies unrevealing. Her urine tested positive for Legionella pneumophila antigen serotype 1 and she improved with antibiotic therapy.



Clinical characteristics and response to newer quinolones in Legionella pneumonia: a report of 28 cases
Santos J, Aguilar L, Garcia-Mendez E, Siquier B, Custardoy J, Garcia-Rey C, Pallares R, Blanquer R, Caminero J, Dal-Re R, Duran J, Gil-Aguado A, Grau I, Ibanez D, Llorca E, Martinez J, Molinos L, Mensa J, Moreno S, Palacios R, Vidal J; 049 Cap Collaborative Study Group.
Infectious Diseases Unit, Hospital Virgen de la Victoria, Malaga, Spain.
J Chemother. 2003 Oct;15(5):461-5.

ABSTRACT: Twenty-eight (11.6%) out of 241 Spanish patients enrolled in an international phase III clinical trial of mild to moderate community-acquired pneumonia (CAP) comparing gemifloxacin vs. trovafloxacin were diagnosed of Legionnaires' disease. A definite diagnosis was established by seroconversion in 13 patients of whom only 2 had a positive Legionella urinary antigen. The remaining 15 patients were possible Legionella infections based on a single elevated IgG titer (> or = 1:512). All patients had a radiologically confirmed diagnosis of pneumonia, 5 (19%) patients were older than 65, comorbidity was present in 9 (33%), and 10 (36%) had to be hospitalized. Fifteen patients were treated with oral gemifloxacin (320 mg/day) and 13 with oral trovafloxacin (200 mg/day). Overall, clinical success occurred in 25 (89.3%) patients after 7 days of treatment and only 1 patient needed a 14-day treatment. There were only one adverse event withdrawal and one clinical failure, and no patients died. In light of the favorable clinical outcome, the use of newer fluoroquinolones seems adequate for the treatment of suspected or proven Legionella pneumonia.



How good is the evidence for the recommended empirical antimicrobial treatment of patients hospitalized because of community-acquired pneumonia? A systematic review

Oosterheert JJ, Bonten MJ, Hak E, Schneider MM, Hoepelman IM.
Division of Medicine, Department of Acute Medicine and Infectious Diseases, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.
J Antimicrob Chemother. 2003 Oct;52(4):555-63.

ABSTRACT: BACKGROUND: For years, monotherapy with a beta-lactam antibiotic (penicillin, amoxicillin or second-generation cephalosporin) was recommended as empirical therapy for patients with community-acquired pneumonia (CAP). A combination of a beta-lactam and a macrolide antibiotic was only recommended for patients with severe CAP needing intensive care treatment or when atypical pathogens, i.e. Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae, were strongly suspected. However, new guidelines recommend a combination of a beta-lactam antibiotic plus a macrolide or monotherapy with a fluoroquinolone for all patients hospitalized with CAP. We evaluated whether treatment with a beta-lactam plus macrolide or quinolone monotherapy is truly superior to beta-lactam treatment alone. METHODS: We systematically reviewed available studies, retrieved from MEDLINE and by hand-searching reference lists from recent reviews and guidelines on the effectiveness of recommended empirical antimicrobial treatment of patients hospitalized because of CAP. RESULTS: Eight relevant studies were selected. In six studies significant reductions in mortality were found, in one study a reduction in hospital length of stay was found and in one study no beneficial effects could be demonstrated for treatment regimens with fluoroquinolone monotherapy or combinations of beta-lactams and macrolides. The beneficial value of macrolides or fluoroquinolones might be the result of a large and mainly unrecognized role of atypical pathogens in the aetiology of CAP, anti-inflammatory effects of macrolides or resistance to beta-lactams of the most important pathogens. However, the studies supporting the recommended treatment regimen were designed as non-experimental cohort studies. As a consequence, the results may have been influenced by confounding by indication. In addition, the outcomes showed several inconsistencies. CONCLUSIONS: A randomized controlled trial is warranted to circumvent the methodological flaws in the designs of the currently available studies. Since the addition of macrolides or treatment with fluoroquinolones may lead to enhanced antibiotic resistance, increased side effects and healthcare-related costs, such a fundamental change in the treatment of CAP should be based on valid data.



Aetiology and Clinical Presentation of Mild Community-Acquired Bacterial Pneumonia

Beovic B, Bonac B, Kese D, Avsic-Zupanc T, Kreft S, Lesnicar G, Gorisek-Rebersek J, Rezar L, Letonja S.
Department of Infectious Diseases, University Medical Centre Ljubljana, Japljeva 2, 1525, Ljubljana, Slovenia.

Eur J Clin Microbiol Infect Dis. 2003 Oct;22(10):584-91.

ABSTRACT: A prospective study was initiated to analyse the bacterial aetiology and clinical picture of mild community-acquired pneumonia in Slovenia using the previously described Pneumonia Severity Index. Radiographically confirmed cases of pneumonia in patients treated with oral antibiotics in seven study centres were included. An aetiological diagnosis was attempted using culture of blood and sputum, urinary antigen testing for Streptococcus pneumoniae and Legionella pneumophila, and antibody testing for Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila in paired serum samples. One hundred thirteen patients were evaluable for clinical presentation and 109 for aetiological diagnosis. At least one pathogen was detected in 62.4% patients. The most common causative agents were Mycoplasma pneumoniae in 24.8%, Chlamydia pneumoniae in 21.1%, and Streptococcus pneumoniae in 13.8% of patients. Dual infection was detected in 8.3% of patients. Most patients suffered from cough, fatigue, and fever. Patients with atypical aetiology of pneumonia differed from those with typical bacterial pneumonia or pneumonia of unknown aetiology in age, presence of dyspnea, and bronchial breathing on lung auscultation. Patients with pneumococcal, chlamydial, and mycoplasmal infections differed in age, risk class, presence of dyspnea, bronchial breathing, and proteinuria. There was an overlap of other clinical symptoms, underlying conditions, and laboratory and radiographic findings among the groups of patients classified by aetiology. Since patients with mild community-acquired pneumonia exhibit similar clinical characteristics and, moreover, since a substantial proportion of cases are attributable to atypical bacteria, broad-spectrum antibiotic treatment seems to be recommended.



Legionella in the veterans healthcare system: report of an eight-year survey
Kelly AA, Danko LH, Kralovic SM, Simbartl LA, Roselle GA.
VA Medical Center, Cincinnati, OH 45220, USA.
Epidemiol Infect. 2003 Oct;131(2):835-9.

ABSTRACT: The Veterans Health Administration (VHA) of the Department of Veterans Affairs tracks legionella disease in the system of 172 medical centres and additional outpatient clinics using an annual census for reporting. In fiscal year 1999, 3.62 million persons were served by the VHA. From fiscal year 1989-1999, multiple intense interventions were carried out to decrease the number of cases and case rates for legionella disease. From fiscal year 1992-1999, the number of community-acquired and healthcare-associated cases decreased in the VHA by 77 and 95.5% respectively (P = 0.005 and 0.01). Case rates also decreased significantly for community and healthcare-associated cases (P = 0.02 and 0.001, respectively), with the VHA healthcare-associated case rates decreasing at a greater rate than VHA community-acquired case rates (P = 0.02). Over the time of the review, the VHA case rates demonstrated a greater decrease compared to the case rates for the United States as a whole (P = 0.02). Continued surveillance, centrally defined strategies, and local implementation can have a positive outcome for prevention of disease in a large, decentralized healthcare system.



In vitro antibacterial potency and spectrum of ABT-492, a new fluoroquinolone
Nilius AM, Shen LL, Hensey-Rudloff D, Almer LS, Beyer JM, Balli DJ, Cai Y, Flamm RK.
Infectious Diseases Research, Abbott Laboratories, Abbott Park, Illinois 60064-3537, USA.

Antimicrob Agents Chemother. 2003 Oct;47(10):3260-9.

ABSTRACT: ABT-492 demonstrated potent antibacterial activity against most quinolone-susceptible pathogens. The rank order of potency was ABT-492 > trovafloxacin > levofloxacin > ciprofloxacin against quinolone-susceptible staphylococci, streptococci, and enterococci. ABT-492 had activity comparable to those of trovafloxacin, levofloxacin, and ciprofloxacin against seven species of quinolone-susceptible members of the family Enterobacteriaceae, although it was less active than the comparators against Citrobacter freundii and Serratia marcescens. The activity of ABT-492 was greater than those of the comparators against fastidious gram-negative species, including Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, and Legionella spp. and against Pseudomonas aeruginosa and Helicobacter pylori. ABT-492 was as active as trovafloxacin against Chlamydia trachomatis, indicating good intracellular penetration and antibacterial activity. In particular, ABT-492 was more active than trovafloxacin and levofloxacin against multidrug-resistant Streptococcus pneumoniae, including strains resistant to penicillin and macrolides, and H. influenzae, including beta-lactam-resistant strains. It retained greater in vitro activity than the comparators against S. pneumoniae and H. influenzae strains resistant to other quinolones due to amino acid alterations in the quinolone resistance-determining regions of the target topoisomerases. ABT-492 was a potent inhibitor of bacterial topoisomerases, and unlike the comparators, DNA gyrase and topoisomerase IV from either Staphylococcus aureus or Escherichia coli were almost equally sensitive to ABT-492. The profile of ABT-492 suggested that it may be a useful agent for the treatment of community-acquired respiratory tract infections, as well as infections of the urinary tract, bloodstream, and skin and skin structure and nosocomial lung infections.


Molecular inflammatory responses measured in blood of patients with severe community-acquired pneumonia

Fernandez-Serrano S, Dorca J, Coromines M, Carratala J, Gudiol F, Manresa F.
Serveis de Pneumologia. Immunologia. Malalties Infeccioses, Hospital Universitari de Bellvitge, Departament de Medicina, Universitat de Barcelona, Barcelona, Spain.
Clin Diagn Lab Immunol. 2003 Sep;10(5):813-20.

ABSTRACT: In order to analyze the characteristics of the inflammatory response occurring in blood during pneumonia, we studied 38 patients with severe community-acquired pneumonia. Venous and arterial blood samples were collected at study entry and on days 1, 2, 3, 5, and 7 after inclusion. The concentrations of proinflammatory (tumor necrosis factor alpha [TNF-alpha], interleukin 1beta [IL-1beta], IL-6, and IL-8) and anti-inflammatory (IL-10) cytokines were determined in order to detect differences related to the origin of the sample, the causative organism, the clinical variables, and the final outcome of the episode. Legionella pneumonia infections showed higher concentrations of TNF-alpha, IL-6, IL-8, and IL-10. After 24 h, plasma IL-6, IL-8, and IL-10 concentrations in pneumococcal episodes increased, whereas in the same time interval, cytokine concentrations in Legionella episodes markedly decreased. The characteristics of the inflammatory response in bacteremic pneumococcal episodes were different from those in nonbacteremic episodes, as indicated by the higher plasma cytokine concentrations in the former group. Finally, our analysis of cytokine concentrations with regard to the outcome--in terms of the need for intensive care unit admittance and/or mechanical ventilation as well as mortality--suggests that there is a direct relationship between the intensity of the inflammatory response measured in blood and the severity of the episode.



Contemporary re-evaluation of the activity and spectrum of grepafloxacin tested against isolates in the United States

Gordon KA, Sader HS, Jones RN.
The JONES Group/JMI Laboratories, North Liberty, IA, USA.

Diagn Microbiol Infect Dis. 2003 Sep;47(1):377-383.

ABSTRACT: Grepafloxacin potency and spectrum of activity were re-evaluated against contemporary pathogens collected from clinical infections in 2001-2002. A total of 995 isolates were tested for grepafloxacin by the reference agar dilution method and these results were compared to those of 25 other antimicrobial agents. Grepafloxacin activity remained comparable to that of ciprofloxacin, levofloxacin and gatifloxacin against Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae (MIC(90), 0.03-2 microg/ml; 0.0-7.7% resistance rates). For Pseudomonas aeruginosa, grepafloxacin was active against ciprofloxacin-susceptible (MIC(90), 2 microg/ml), but not against ciprofloxacin-resistant (MIC(90), >8 microg/ml) isolates. Against methicillin-susceptible Staphylococcus aureus, grepafloxacin susceptibility rate was 91.4%, equal to that of levofloxacin. None of the fluoroquinolones showed reasonable activity against methicillin-resistant staphylococci. Gatifloxacin and grepafloxacin had the same MIC(90) against beta-hemolytic streptococci (0.25 microg/ml) and penicillin-susceptible Streptococcus pneumoniae (0.25 microg/ml). Grepafloxacin and other fluoroquinolone activities were not influenced by penicillin resistance in S. pneumoniae. Grepafloxacin was very active against Haemophilus influenzae (MIC(90), 0.03 microg/ml), Moraxella catarrhalis (MIC(90), 0.03 microg/ml) and Legionella spp. (MIC(90), 0.5 microg/ml). These results on recently isolated organisms indicate that grepafloxacin has a sustained potency and spectrum against most clinically important and indicated pathogens.


High-dose, short-course levofloxacin for community-acquired pneumonia: a new treatment paradigm

Dunbar LM, Wunderink RG, Habib MP, Smith LG, Tennenberg AM, Khashab MM, Wiesinger BA, Xiang JX, Zadeikis N, Kahn JB.
Louisiana State University Medical Center, New Orleans, Louisiana, USA.
Clin Infect Dis. 2003 Sep 15;37(6):752-60.
ABSTRACT: Levofloxacin demonstrates concentration-dependent bactericidal activity most closely related to the pharmacodynamic parameters of the ratio of area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) and the ratio of peak plasma concentration (C(max)) to MIC. Increasing the dose of levofloxacin to 750 mg exploits these parameters by increasing peak drug concentrations, allowing for a shorter course of treatment without diminishing therapeutic benefit. This was demonstrated in a multicenter, randomized, double-blind investigation that compared levofloxacin dosages of 750 mg per day for 5 days with 500 mg per day for 10 days for the treatment of mild to severe community-acquired pneumonia (CAP). In the clinically evaluable population, the clinical success rates were 92.4% (183 of 198 persons) for the 750-mg group and 91.1% (175 of 192 persons) for the 500-mg group (95% confidence interval, -7.0 to 4.4). Microbiologic eradication rates were 93.2% and 92.4% in the 750-mg and 500-mg groups, respectively. These data demonstrate that 750 mg of levofloxacin per day for 5 days is at least as effective as 500 mg per day for 10 days for treatment of mild-to-severe CAP.


Documentation of Legionella pneumophila and Mycobacterium tuberculosis co-existence in a patient with acute respiratory distress syndrome

Metaxa-Mariatou V, Ikonomou A, Tzortzi A, Mihalatos M, Vakalis N, Nasioulas G.

Molecular Biology Research Center, HYGEIA Antonis Papayiannis, Kifissias Ave. & 4 Erythrou Stavrou Str., 151 23 Maroussi, Athens, Greece.

In Vivo. 2003 Jul-Aug;17(4):365-7.

BACKGROUND: Bacterial lung infections are common causes of ARDS and, despite intensive research for decades, the mortality rate remains very high. Only two reports suggest the co-existence of Legionnaires' disease and pulmonary tuberculosis based mainly on clinical presentation and serologic results for Legionella and positive cultures for Mycobacterium tuberculosis (M. tuberculosis). MATERIALS AND METHODS: A variety of specimens from a 61-year-old man was used for detection of Legionella pneumophila (L. pneumophila) and M. tuberculosis by PCR. Further identification of the pathogens was carried out by sequence analysis. RESULTS: L. pneumophila region mip was detected in bronchial washings, bronchoalveolar lavage and urine specimens of the patient. M. tuberculosis regions IS6110 and mtp40 were detected in endo-bronchial secretions and bronchoalveolar lavage. CONCLUSION: By using polymerase chain reaction (PCR) and DNA sequencing we documented L. pneumophila and M. tuberculosis co-existence, in multiple specimens of a patient presenting with acute respiratory distress syndrome (ARDS). Furthermore, the efficacy of the specific antibiotic treatment, based on the PCR results, suggest the co-existence of these two pathogens.


Chest CT findings and clinical features in mild Legionella pneumonia

Yagyu H, Nakamura H, Tsuchida F, Sudou A, Kishi K, Oh-ishi S, Matsuoka T.

Fifth Department of Internal Medicine, Tokyo Medical University, Tokyo Medical University, Kasumigaura Hospital, Ibaraki.

Intern Med. 2003 Jun;42(6):477-82.

OBJECTIVE: To evaluate mild Legionella pneumonia (LP) by chest CT, and clinical features. PATIENTS: In June 2000, an outbreak of LP occurred in Japan. Eight patients with mild LP (seven men, one woman; mean age 55.9 years) had fevers of more than 38 degrees C, but respiratory symptoms were observed only in four. Chest CT was performed before starting an appropriate treatment. MEASUREMENT: CT images were assessed by the distribution of ground-glass opacity (GGO), consolidation, and the existence of pleural effusion. RESULTS: Chest CT findings: multiple segments were affected in all of the patients, (pleural effusion in three, peripheral lung consolidation in seven, and GGO in seven). GGO was located around the consolidation in six patients. CONCLUSION: Mild LP may present as fever without respiratory symptoms. Chest CT findings of mild LP are bilateral, multiple affected segments and peripheral lung consolidation with GGO.



Maximizing efficacy and reducing the emergence of resistance

Wise R.

Department of Medical Microbiology, City Hospital , Birmingham B18 7QH , UK.

J Antimicrob Chemother. 2003 May; 51 Suppl 1: 37 -42.

ABSTRACT: An understanding of the pharmacokinetic and pharmacodynamic properties of antimicrobial agents enables better choices to be made in the clinical situation. The fluoroquinolones share several useful pharmacokinetic properties, such as good bioavailability (in most cases >85%) and the ability to penetrate and concentrate intracellularly, giving them activity against pathogens such as Legionella pneumophila and Listeria monocytogenes. Nevertheless, there are some important differences between the fluoroquinolones, and even the newer fluoroquinolones demonstrate a range of pharmacodynamic properties. When considering the area under the inhibition curve (AUIC) and the Cmax/MIC, the comparative figures are: ciprofloxacin and ofloxacin (5-25, 1-5); levofloxacin, grepafloxacin and gatifloxacin (25-75, 5-10); trovafloxacin (75-250, 10-20) and moxifloxacin, clinafloxacin and gemifloxacin (>250, >20). The development of resistance is also a concern, and selecting an agent that reaches an adequate concentration above the MIC will reduce the opportunity for resistance to develop. These properties should be considered when selecting a fluoroquinolone either for inclusion in a formulary, or for use in an individual patient.


Legionnaires' disease: a rational approach to therapy

Roig J, Rello J.

Pulmonary Division, Hospital Nostra Senyora de Meritxell, Escaldes-Engordany, Principality of Andorra.

J Antimicrob Chemother. 2003 May; 51(5):1119-29.

ABSTRACT: Optimal therapy against Legionella infection is based on agents with a high intrinsic activity, an appropriate pharmacokinetic and pharmacodynamic profile (including the ability to penetrate phagocytic cells), a low incidence of adverse reactions and an advantageous cost-efficacy relationship. Newer macroazalides and fluoroquinolones are among the first-line therapies and in severe infections, particularly those occurring in immunocompromised patients, azithromycin and later fluoroquinolones are the agents of choice. Delay in the onset of adequate therapy is a key factor associated with a poor outcome. Thus, all patients with pneumonia associated with respiratory failure, shock or underlying disease causing severe immunodeficiency should initially receive an agent active against Legionella spp., at least while the aetiology remains unknown. Adjunctive measures improve outcome in critically ill patients. In intubated patients with delayed resolution, superinfection by Pseudomonas aeruginosa or co-infection caused by other pathogens should be excluded.



Severe community-acquired pneumonia: what's in a name?

Oosterheert JJ, Bonten MJ, Hak E, Schneider MM, Hoepelman AI.

Division of Medicine, Department of Acute Medicine and Infectious Diseases, University Medical Center Utrecht, The Netherlands.

Curr Opin Infect Dis. 2003 Apr; 16(2): 153-9.

ABSTRACT: PURPOSE OF REVIEW: Formerly, patients with community-acquired pneumonia admitted to an intensive care unit were considered as having the severe form of the disease. Recently, guidelines have distinguished severe and non-severe community-acquired pneumonia based on clinical definitions. In this review, we describe the different definitions of severe community-acquired pneumonia, and whether a differentiation based on these definitions reflects variation in etiology, risk factors, diagnostic approaches and treatment. RECENT FINDINGS: New definitions do not seem to accurately identify patients with high risks of mortality; patients not admitted to an intensive care unit could also be diagnosed as having severe community-acquired pneumonia. Host-factors, such as genetic factors and underlying diseases, can influence severity of presentation of community-acquired pneumonia. Distribution of pathogens in severe and non-severe disease forms is comparable. Initial antibiotic therapy in patients with severe disease should provide coverage of Streptococcus pneumoniae and Legionella pneumophila, as delay is associated with worse outcomes. However, recent studies also suggested an additional benefit of atypical coverage in non-severe disease. As a result, initial therapy with a beta-lactam plus a macrolide or an anti-pneumococcal fluoroquinolone is recommended for all patients with community-acquired pneumonia. Furthermore, the value of vaccination against pneumococci to prevent episodes of severe disease is yet unknown. SUMMARY: As current guidelines do not adequately identify patients with high risk of mortality and intensive care unit admittance, clinical judgment remains important. Based on distribution of pathogens, investigational procedures and therapy recommended in recent guidelines, differentiation between severe and non-severe community-acquired pneumonia does not seem useful. Whether atypical coverage indeed has additional value in non-severe or pneumococcal CAP, however, remains to be determined. In addition, the preventive benefit of influenza and pneumococcal vaccination for development of SCAP awaits further evidence.