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                     Clinica e terapia (2020 - 2017)

                     [ultimo aggiornamento 25/11/2020]


Epileptic Seizure after Use of Moxifloxacin in Man with Legionella longbeachae Pneumonia

Wang JY, Li X, Chen JY, Tong B.

Department of Internal Medicine, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Jiangxi, China;

Emerg Infect Dis 2020 Nov;26(11):2725-2727.

Abstract: Legionellosis caused by Legionella longbeachae is diagnosed mainly by PCR. We report a case of L. longbeachae infection in mainland China, which was diagnosed by metagenomic next-generation sequencing, in a man who developed an epileptic seizure after using moxifloxacin. Metagenomic next-generation sequencing may be a useful tool to detect Legionella spp.


Antibiotic Resistance of Legionella pneumophila in Clinical and Water Isolates-A Systematic Review

Pappa O, Chochlakis D, Sandalakis V, Dioli C, Psaroulaki A, Mavridou A.

Department of Biomedical Sciences, University of West Attica, 12243 Egaleo, Greece.

Int J Environ Res Public Health 2020 Aug 11;17(16):5809.

Abstract: The current systematic review investigates the antibiotic susceptibility pattern of Legionella pneumophila isolates from the 1980s to the present day, deriving data from clinical and/or water samples from studies carried out all over the world. Eighty-nine papers meeting the inclusion criteria, i.e., "Legionella pneumophila" and "resistance to antibiotics", were evaluated according to pre-defined validity criteria. Sixty articles referred to clinical isolates, and 18 articles reported water-related L. pneumophila isolates, while 11 articles included both clinical and water isolates. Several methods have been proposed as suitable for the determination of MICs, such as the E-test, broth and agar dilution, and disk diffusion methods, in vivo and in vitro, using various media. The E-test method proposed by the European Society of Clinical Microbiology and Infectious Diseases (EUCAST) seems to be the second most frequently used method overall, but it is the preferred method in the most recent publications (2000-2019) for the interpretation criteria. Erythromycin has been proved to be the preference for resistance testing over the years. However, in the last 19 years, the antibiotics ciprofloxacin (CIP), erythromycin (ERM), levofloxacin (LEV) and azithromycin (AZM) were the ones that saw an increase in their use. A decrease in the sensitivity to antibiotics was identified in approximately half of the reviewed articles.


Efficacy of delafloxacin versus moxifloxacin against atypical bacterial respiratory pathogens in adults with community-acquired bacterial pneumonia (CABP): Data from the Delafloxacin Phase 3 CABP Trial

McCurdy S, Nenninger A, Sheets A, Keedy K, Lawrence L, Quintas M, Cammarata S.

Melinta Therapeutics, Morristown, NJ, USA.

Int J Infect Dis 2020 Aug;97:374-379.

Abstract: Objectives: To report atypical pathogens from clinical trial data comparing delafloxacin to moxifloxacin in the treatment of adults with community-acquired bacterial pneumonia (CABP). Methods: Multiple diagnostic methods were employed to diagnose atypical infections including culture, serology, and urinary antigen. Results: The microbiological intent-to-treat (MITT) population included 520 patients; 30% had an atypical bacterial pathogen identified (156/520). Overall, 13.1% (68/520) had a monomicrobial atypical infection and 2.3% (12/520) had polymicrobial all-atypical infections. Among patients with polymicrobial infections, Streptococcus pneumoniae was the most frequently occurring co-infecting organism and Chlamydia pneumoniae was the most frequently occurring co-infecting atypical organism. For Mycoplasma pneumoniae and Legionella pneumophila, serology yielded the highest number of diagnoses. Delafloxacin and moxifloxacin had similar in vitro activity against M. pneumoniae and delafloxacin had greater activity against L. pneumophila. Two macrolide-resistant M. pneumoniae isolates were recovered. No fluoroquinolone-resistant M. pneumoniae were isolated. The rates of microbiological success (documented or presumed eradication) at test-of-cure were similar between the delafloxacin and moxifloxacin groups. There was no evidence of a correlation between minimum inhibitory concentration (MIC) and outcome; a high proportion of favorable outcomes was observed across all delafloxacin baseline MICs. Conclusions: Delafloxacin may be considered a treatment option as monotherapy for CABP in adults, where broad-spectrum coverage including atypical activity is desirable.


Fatal Fulminant Legionnaires' Disease in a Patient on Maintenance Hemodialysis

Kawashima A, Katagiri D, Kondo I, Sakamoto E, Suzuki M, Arai Y, Sato F, Tada M, Hinoshita F.

Department of Nephrology, National Center for Global Health and Medicine, Japan.

Intern Med 2020 Aug 1;59(15):1913-1918.

Abstract: We herein report a case of fulminant Legionnaires' disease with autopsy findings in a patient on maintenance hemodialysis (HD). Chronic kidney disease is a strong risk factor for Legionnaires' disease, although there have been only a few reports in HD patients. Because most patients on HD are anuric, the use of rapid assay kits to detect antigens in urine samples for the diagnosis of Legionnaires' disease is not always feasible. We suggest the use of clinical predictive tools or the loop-mediated isothermal amplification (LAMP) method, which can be applied for anuric patients, such as those on HD, with pneumonia.


Cutaneous Legionella infections in allogeneic hematopoietic cell transplantation recipients

Vaidya T, Schmidt E, Papanicolaou G, Hauser J, Lezcano C, Tang YW, Markova A.

Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY Department of Dermatology, Weill Cornell Medical College, New York, NY.

Dermatol Online J 2020 Jun 15;26(6):13030/qt05f926n7.

Abstract: To date, only twenty cases of cutaneous legionellosis have been reported. Cutaneous legionellosis has heterogeneous manifestations including abscesses, nodules, and cellulitis. The detection of most cutaneous Legionella species requires specific diagnostic cultures and assays. Herein, we report a case of cutaneous legionella in a hematopoietic cell transplantation recipient with culture-negative nodules unresponsive to empiric antibiotics. We also discuss the varied morphology of cutaneous legionellosis and important diagnostic considerations.


Diffuse alveolar hemorrhage due to Legionella pneumophila serogroup 3

Chowdhury A, Khan SA, Haugh S.

Department of Hospital Medicine, Mayo Clinic Health System, Mankato, MN, USA.

J Community Hosp Intern Med Perspect 2020 Jun 14;10(3):262-264.

Abstract: Legionella pneumophilia remains an important cause of pneumonia that can cause substantial clinical morbidity and mortality. We describe a case involving a 67-year-old woman with legionella pneumonia who developed diffuse alveolar haemorrhage. We also highlight the pitfalls of commonly used legionella urine antigen testing. Furthermore, we explore the role of high-dose steroid therapy as a treatment option for patients with diffuse alveolar haemorrhage secondary to legionella pneumonia who continue to deteriorate in spite of adequate antimicrobial therapy.


Persistent Legionnaires' Disease and Associated Antibiotic Treatment Engender a Highly Disturbed Pulmonary Microbiome Enriched in Opportunistic Microorganisms

Pérez-Cobas AE, Ginevra C, Rusniok C, Jarraud S, Buchrieser C.

Institut Pasteur, Biologie des Bactéries Intracellulaires, Paris, France.

mBio 2020 May 19;11(3):e00889-20.

Abstract: Despite the importance of pneumonia to public health, little is known about the composition of the lung microbiome during infectious diseases, such as pneumonia, and how it evolves during antibiotic therapy. To study the possible relation of the pulmonary microbiome to the severity and outcome of this respiratory disease, we analyzed the dynamics of the pathogen and the human lung microbiome during persistent infections caused by the bacterium Legionella pneumophila and their evolution during antimicrobial treatment. We collected 10 bronchoalveolar lavage fluid samples from three patients during long-term hospitalization due to pneumonia and performed a unique longitudinal study of the interkingdom microbiome, analyzing the samples for presence of bacteria, archaea, fungi, and protozoa by high-throughput Illumina sequencing of marker genes. The lung microbiome of the patients was characterized by a strong predominance of the pathogen, a low diversity of the bacterial fraction, and an increased presence of opportunistic microorganisms. The fungal fraction was more stable than the bacterial fraction. During long-term treatment, no genomic changes or antibiotic resistance-associated mutations that could explain the persistent infection occurred, according to whole-genome sequencing analyses of the pathogen. After antibiotic treatment, the microbiome did not recover rapidly but was mainly constituted of antibiotic-resistant species and enriched in bacteria, archaea, fungi, or protozoa associated with pathogenicity. The lung microbiome seems to contribute to nonresolving Legionella pneumonia, as it is strongly disturbed during infection and enriched in opportunistic and/or antibiotic-resistant bacteria and microorganisms, including fungi, archaea, and protozoa that are often associated with infections. IMPORTANCE: The composition and dynamics of the lung microbiome during pneumonia are not known, although the lung microbiome might influence the severity and outcome of this infectious disease, similar to what was shown for the microbiome at other body sites. Here we report the findings of a comprehensive analysis of the lung microbiome composition of three patients with long-term pneumonia due to L. pneumophila and its evolution during antibiotic treatment. This work adds to our understanding of how the microbiome changes during disease and antibiotic treatment and points to microorganisms and their interactions that might be beneficial. In addition to bacteria and fungi, our analyses included archaea and eukaryotes (protozoa), showing that both are present in the pulmonary microbiota and that they might also play a role in the response to the microbiome disturbance.


In Vitro and Intracellular Activities of Omadacycline against Legionella pneumophila

Dubois J, Dubois M, Martel JF.

M360 Inc., Sherbrooke, Québec, Canada.

Antimicrob Agents Chemother 2020 Apr 21;64(5):e01972-19.

Abstract: Omadacycline is an aminomethylcycline antibiotic with in vitro activity against pathogens causing community-acquired bacterial pneumonia (CABP). This study investigated the activity of omadacycline against Legionella pneumophila strains isolated between 1995 and 2014 from nosocomial or community-acquired respiratory infections. Omadacycline exhibited extracellular activity similar to comparator antibiotics; intracellular penetrance was found by day 3 of omadacycline exposure. These results support the utility of omadacycline as an effective antibiotic for the treatment of CABP caused by L. pneumophila.


Persistently positive culture of antimicrobial-susceptible Legionella pneumophila despite appropriate therapy

Rafiei N, Shaw B, Dendle C, Opat S, Williamson D, Graham M.

Monash Infectious Diseases, Monash Health, Clayton, Victoria, Australia.

Access Microbiol. 2020 Mar 2;2(5):acmi000113.

Abstract: Legionella pneumophila is a well-known cause of pneumonia that is infrequently cultured in clinical practice. We report a case of an immunocompromised patient with persistently positive L. pneumophila cultures from invasive respiratory samples despite prolonged treatment with appropriate antibiotics. In vitro testing showed that the isolate remained susceptible to ciprofloxacin and azithromycin.


Transient Parkinsonism Associated with Acute Legionnaires' Disease

Su JS, Honsberger S, Husnain MG.

MetroHealth Medical Center, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

BMJ Case Rep 2020 Jan;13(1):e233152. 

Abstract: A 44-year-old right-handed man with a 5-day history of non-productive cough associated with subjective fevers/chills and night sweats presented to the emergency department with slurred speech. Radiography and urine antigen testing confirmed the diagnosis of Legionella pneumonia. The hospital course was complicated by acute hypoxic respiratory failure that required 7 days of invasive mechanical ventilation. Following extubation, the patient had dysarthria and developed new parkinsonism features. Brain imaging revealed a non-specific focal lesion in the left frontal lobe of unclear significance. Ciprofloxacin was decided as the final antibiotic of choice for its favourable central nervous system profile. Levodopa-carbidopa was initiated to help activate the basal ganglia. The patient had complete resolution of pneumonia and transient parkinsonism. He was able to regain most of his baseline functional status with intensive rehabilitation.


Legionella Pneumonia in Late Pregnancy

Mosaad-Boktor HK, Lee SA.

Hospitalist Department, Arnot Ogden Medical Center, Elmira, NY, USA.

Am J Case Rep 2019 Dec;20:1956-1960.

Abstract: BACKGROUND Legionella pneumonia can be an aggressive form of pneumonia. However, it is rare in pregnant women, particularly in the peripartum period. To the best of our knowledge this is the only case of Legionella pneumonia with endometrial sepsis. We are reporting a patient with this rare condition. CASE REPORT The patient was an 18-year-old female, pregnant with her first baby, who developed symptoms of the common cold near term. The patient was seen at another major facility initially and was discharged home with a diagnosis of "cold". She was still uncomfortable and came to our facility Aront Ogden Medical Center Elmira, NY, USA, where she had rupture of membranes and underwent C-section. She was suspected clinically of having pneumonia. Initial chest x-ray was negative, but computed tomography (CT)-scan did show bilateral pneumonia. Further workup confirmed the diagnosis of Legionella pneumonia and was treated for that as well as for endometritis. She did require Intensive Care Unit (ICU) care during her hospital stay. The patient was seen and evaluated by multiple subspecialties, including Critical Care, Infectious Disease, and Gastroenterology subspecialties. The patient improved steadily and was later discharged home in the care of her family with a healthy baby and was advised to follow up with her Primary Medical Provider as outpatient. CONCLUSIONS Legionella pneumonia in pregnancy may be more common than we think, and could be easily overlooked in that patient population, have to be in the back mind of medical provider. Overlooking diagnosis could lead to serious adverse consequences for these patients.


Prosthetic Valve Legionella Endocarditis

Young JS, Farber BF, Pupovac SS, Graver LM.

Department of Cardiovascular and Thoracic Surgery, Hofstra Northwell School of Medicine, Manhasset, New York.

Ann Thorac Surg 2019 Oct;108(4):e271-e272.

Abstract: This report describes the case of an 80-year-old man with culture-negative prosthetic valve endocarditis who ultimately was given a diagnosis of Legionella pneumophila endocarditis.


Antibiotic Resistance and Azithromycin Resistance Mechanism of Legionella Pneumophila Serogroup 1 in China

Jia X, Ren H, Nie X, Li Y, Li J, Qin T.

State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing, China.

Antimicrob Agents Chemother 2019 Sep;63(10):e00768-19.

Abstract: Legionnaires' disease, caused by Legionella pneumophila, has been treated primarily with antibiotics. However, few reports have been published on antibiotic-resistant Legionella in China. Our aim was to determine the azithromycin resistance mechanism of L. pneumophila serogroup 1 in China. The sensitivities of 149 L. pneumophila serogroup 1 strains, isolated from clinical cases or environmental water in China from 2002 to 2016, to five antibiotics, including erythromycin, azithromycin, levofloxacin, moxifloxacin, and rifampin, were evaluated. The mechanisms of the resistance of L. pneumophila serogroup 1 to azithromycin were studied. The expression levels of efflux pump gene lpeAB and the MIC of azithromycin-resistant strains in the presence and absence of the efflux pump inhibitor carbonyl cyanide-chlorophenylhydrazone (CCCP) were determined. All 149 strains were sensitive to erythromycin, levofloxacin, moxifloxacin, and rifampin, among which 25 of the strains exhibited azithromycin resistance. These 25 strains, including strains of sequence type 1 (ST1), ST144, ST150, ST154, and ST629, were screened. Expression of lpeAB was responsible for the reduced azithromycin susceptibility in all 25 of these strains. The phenotypes of 25 strains with virulence were linked by evaluating the intracellular growth ability in mouse macrophage J774 cells. Among the 25 strains, 60% were more virulent than the ATCC 33152 reference strain. The results determined in our study represent data supporting the further study of the antibiotic sensitivity of L. pneumophila strains in China.


Legionella Co-Infection in HIV-associated Pneumonia

Head BM, Trajtman A, Bernard K, Burdz T, Vélez L, Herrera M, Rueda ZV, Keynan Y.

Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada;

Diagn Microbiol Infect Dis 2019 Sep;95(1):71-76.

Abstract: Due to poor diagnostics and increased co-infections, HIV-associated Legionella infections are underreported. We aimed to retrospectively determine the frequency of Legionella infections in bronchoalveolar lavage (BAL) from HIV-associated pneumonia patients hospitalized in Medellin, Colombia, between February 2007 and April 2014. Although culture was negative, 17 BAL (36%) were positive for Legionella by quantitative polymerase chain reaction, most of which were in the Mycobacterium tuberculosis or Pneumocystis jirovecii co-infected patients, and included L. anisa (n=6), L. bozemanae (n=4), L. pneumophila (n=3), and L. micdadei (n=2). All L. bozemanae and L. micdadei associated with Pneumocystis, while all L. pneumophila associated with M. tuberculosis. Legionella probable cases had more complications and higher mortality rates (P=0.02) and were rarely administered empirical anti-Legionella therapy while in hospital. Clinicians should be aware of the possible presence of Legionella in HIV and M. tuberculosis or P. jirovecii co-infected patients.


An Unusual Presentation of Legionella Pneumonia in a Returning Traveller

Shorten RJ, Norman J, Sweeney LC.

Microbiology, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK.

BMJ Case Rep 2019 Aug;12(8):e230130.

Abstract: A male patient in his mid-60s presented with a severe pneumonia following return to the UK after travel to Crete. He was diagnosed with Legionnaire's disease (caused by an uncommon serogroup of Legionella pneumophila). He was pancytopenic on admission, and during a long stay on critical care he was diagnosed with a disseminated Aspergillus infection. Bone marrow aspiration revealed an underlying hairy cell leukaemia that undoubtedly contributed to his acute presentation and subsequent invasive fungal infection.


Severe Transient Left Ventricular Dysfunction in a Patient with Legionella Pneumophila Pneumonia

Elikowski W, Małek-Elikowska M, Greberska W, Fertała N, Zawodna M, Marchlewska J, Dudziak J.

Józef Struś Hospital, Department of Internal Medicine, Poznań, Poland.

Pol Merkur Lekarski 2019 Jul;47(277):19-24.

Abstract: Legionella pneumophila infection (legionellosis) usually presents as a multisystemic disease, predominantly affecting the lungs (Legionnaires' disease - LD). Immunodeficiency, chemotherapy or chronic steroids use increase the risk of developing LD. Extrapulmonary manifestations of LD include cardiac complications: myocarditis, pericarditis or endocarditis. A case report: The authors describe a case of a 51-year-old female with a history of cryoglobulinemic vasculitis, Sjögren syndrome and chronic lymphocytic leukemia who was admitted due to a high fever, fatigue, tachycardia, dyspnea and cough. Chest X-ray and CT showed bilateral pulmonary infiltrations and pleural effusion. LD was diagnosed on positive L. pneumophila urinary antigen test. Echocardiography revealed severe left ventricular (LV) dysfunction with substantially decreased ejection fraction and global longitudinal strain (GLS), with a pattern resembling reverse takotsubo syndrome (rTTS). The coronary arteries in non-invasive coronary angiography were normal. During therapy with levofloxacin and intravenous immunoglobulins as well as with carvedilol, ramipril and diuretics, gradual clinical improvement with complete normalization of LV function was observed within 5 weeks. Cardiac magnetic resonance (CMR) performed on day 35 revealed only small intramural foci of late gadolinium enhancement (LGE) with localization not corresponding to the most decreased regional longitudinal strain in the initial echocardiographic examination. The authors suggest that the mechanism of transient LV dysfunction in the case presented may have been of complex nature, including LD myocarditis and stress-induced cardiomyopathy (with the prevalence of the latter) which has not so far been reported in the literature.


A Case of Legionnaire's Endophthalmitis

Yu JH, Avaylon J, Kil H, Kim JK, Gallemore RP.

Department of Clinical Research, Retina Macula Institute, Torrance, CA, USA.

Int Med Case Rep J 2019 Jun;12:173-177.

Abstract: Purpose: To report a case of endophthalmitis associated with Legionella pneumophila. Case Report: A 46-year-old, highly myopic male with a complex history of recurrent retinal detachments, macular hole, cataract surgery and an infected scleral buckle in the left eye, presented with pain, redness, hypopyon and vision loss in the left eye, 14 days following blunt head trauma. Empirical treatment for endophthalmitis with intravitreal injections of Vancomycin and Ceftazidime afforded minimal improvement. He developed recurrent hypopyon and underwent vitrectomy surgery with intravitreal antibiotic injections at the time of surgery and had improvement. Intraoperative culture was positive for Legionella pneumophila. He had continued episodes of recurrent inflammation which were quelled by intravitreal moxifloxacin injections performed every 3-10 days. He developed a recurrent RD with proliferative vitreoretinopathy (PVR) and underwent vitrectomy with silicone oil. The retina was reattached but had no light perception vision in the affected eye. Conclusion: When endophthalmitis is contracted in a work-place setting, a culture for L. pneumophila should be considered. A combination of intravitreal moxifloxacin and oral azithromycin may be effective.


Pneumonia and Pulmonary Abscess Due to Legionella micdadei in an Immunocompromised Patient

Foissac M, Bergon L, Vidal J, Cauquil P, Mainar A, Mourguet M.

MD, Service de Maladies infectieuses, Centre Hospitalier Castres-Mazamet, Castres, France.

Germs 2019 Jun;9(2):89-94.

Abstract: Introduction: Legionella micdadei are gram-negative bacilli living in soil and aquatic habitats. They are responsible for less than 10% of legionellosis but have a propensity to affect people suffering from immunodeficiency. Lung cavitations may also occur in this population. Isolation of L. micdadei on clinical samples requires specific culture media that are not routinely used. Moreover, serologic methods and urinary assays are specific for Legionella pneumophila serogroup 1 (the most frequent serogroup isolated from clinical specimens), and lack sensitivity for diagnosing L. micdadei infection. As a consequence, this diagnosis is difficult to confirm. Case report: We report here a severe case of community-acquired legionellosis due to L. micdadei, in a patient under immunosuppressive medications and high-dose corticosteroids for rheumatoid arthritis. The source of his infection was hypothesized to be his continuous positive airway pressure device, which was regularly cleaned with tap water instead of sterile water, thus potentially resulting in Legionella contamination. Conclusions: L. micdadei must be considered as a possible cause of community-acquired severe pneumonia in case of immunodeficiency. For outpatients, advice concerning the cleaning of aerosols-generating devices at home must be emphasized.


Validation of a Prediction Rule for Legionella Pneumonia in Emergency Department Patients

Bolliger R, Neeser O, Merker M, Vukajlovic T, Felder L, Fiumefreddo R, Haubitz S, Koch D, Hammerer-Lercher A, Ottiger C, Fux CA, Mueller B, Schuetz P.

Department of General Internal and Emergency Medicine, University, Aarau, Switzerland.

Open Forum Infect Dis 2019 Jun;6(7):ofz268.

Abstract: We validated a clinical prediction rule for Legionella based on clinical parameters (dry cough, fever) and laboratory findings (C-reactive protein, lactate dehydrogenase, sodium, platelet counts) in 713 consecutive patients with community-acquired pneumonia. The Legionella Score performed well in estimating the likelihood for Legionella infection and thus may help to direct diagnostic and therapeutic decisions.


Legionella Pneumonia Complicated by Rhabdomyolysis

Sutarjono B, Alexis J, Sachidanandam JC.

Internal Medicine, Brookdale University Hospital Medical Center, Brooklyn, New York, USA.

BMJ Case Rep. 2019 Jun 20;12(6):e229243. 

Abstract: Legionnaires' disease is a recognised but rare cause of rhabdomyolysis. It can be further complicated with renal impairment. In this case report, we describe a previously healthy, semi active 50-year-old man who within days was reduced to having periods of dyspnea after minutes of walking in addition to near fatal acute renal failure. He was found to have the rare triad of Legionella pneumonia, renal failure and rhabdomyolysis, which is associated with high morbidity and mortality. He was treated according to guidelines with azithromycin monotherapy and aggressive fluid hydration. 20 days after admission, the patient was walking independently and discharged home.


Susceptibility of Legionella pneumophila to Antimicrobial Agents and the Presence of the Efflux Pump LpeAB

Natås OB, Brekken AL, Bernhoff E, Hetland MAK, Löhr IH, Lindemann PC.

Department of Medical Microbiology, Stavanger University Hospital, Stavanger, Norway.

J Antimicrob Chemother 2019 Jun;74(6):1545-1550.

Abstract: Objectives: Legionella pneumophila strains resistant to antimicrobial agents are rare. We tested 10 antimicrobial agents against clinical and environmental strains and performed WGS to screen for the presence of resistance mechanisms. Methods: A total of 122 clinical and environmental strains of L. pneumophila collected between 2000 and 2017 and characterized by serogroup and ST were included. Antimicrobial susceptibility was tested by gradient diffusion tests on buffered charcoal yeast extract agar medium supplemented with α-ketoglutarate (BCYE-α) and a subgroup of strains were whole-genome sequenced using Illumina technology and analysed. Results: All strains showed a WT MIC distribution for ciprofloxacin, levofloxacin, moxifloxacin, rifampicin, cefotaxime, tetracycline and trimethoprim/sulfamethoxazole. All strains of L. pneumophila serogroup 1, ST1 (18/122; 14.7%) showed reduced susceptibility to azithromycin (MIC 0.5-1 mg/L) and harboured the efflux pump component lpeAB. Two strains of L. pneumophila serogroup 5 (ST1328) and one strain of serogroup 4 (ST1973) also showed reduced susceptibility to azithromycin (MIC 0.5 mg/L). They harboured lpeAB gene variants with 91.37% and 92.52% nucleotide identity, respectively, compared with the lpeAB genes of serogroup 1, ST1 strains. Conclusions: Our collection of L. pneumophila strains was susceptible to most antimicrobial agents except azithromycin. Gradient diffusion tests on BCYE-α test medium detected strains with reduced susceptibility to azithromycin. All L. pneumophila serogroup 1, ST1 strains showed reduced susceptibility to macrolides and contained the efflux pump component lpeAB. Reduced susceptibility to azithromycin in non-serogroup 1 strains may be due to the presence of an lpeAB efflux pump variant.


Antibiotic Susceptibility of Environmental Legionella pneumophila Isolated in India

Sreenath K, Chaudhry R, Vinayaraj EV, Thakur B.

Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India.

Future Microbiol 2019 May;14:661-669.

Abstract: Aim: Data are limited regarding the antibiotic susceptibility of Legionella pneumophila in India. The aim of this study was to determine the drug susceptibility of environmental L. pneumophila isolates in India for antibiotics commonly used in clinical practice for Legionnaires' disease treatment. Materials & methods: The activities of seven antibiotics against 46 environmental isolates of L. pneumophila were evaluated by using E-test on buffered charcoal yeast extract-α agar. Results: Among the L. pneumophila isolates tested, no tendency toward drug resistance was observed. Rifampicin was the most potent drug followed by levofloxacin, while doxycycline and tetracycline were found to be the less active agents. Conclusion: Susceptibility testing of Legionella environmental isolates could be beneficial to notify resistance to antibiotics in the environment before it becomes evident in clinical strains.


Emerging Respiratory Infections: The Infectious Disease Pathology of SARS, MERS, Pandemic Influenza, and Legionella

Bradley BT, Bryan A.

University of Washington, Department of Laboratory Medicine, Seattle, USA.

Semin Diagn Pathol 2019 May;36(3):152-159.

Abstract: Lower respiratory infections remain one of the top global causes of death and the emergence of new diseases continues to be a concern. In the first two decades of the 21st century, we have born witness to the emergence of newly recognized coronaviruses that have rapidly spread around the globe, including severe acute respiratory syndrome virus (SARS) and Middle Eastern respiratory syndrome virus (MERS). We have also experienced the emergence of a novel H1N1 pandemic influenza strain in 2009 that caused substantial morbidity and mortality around the world and has transitioned into a seasonal strain. Although we perhaps most frequently think of viruses when discussing emerging respiratory infections, bacteria have not been left out of the mix, as we have witnessed an increase in the number of infections from Legionella spp. since the organisms' initial discovery in 1976. Here, we explore the basic epidemiology, clinical presentation, histopathology, and clinical laboratory diagnosis of these four pathogens and emphasize themes in humans' evolving relationship with our natural environment that have contributed to the infectious burden. Histology alone is rarely diagnostic for these infections but has been crucial to bettering our understanding of these diseases. Together, we rely on the diagnostic acumen of pathologists to identify the clinicopathologic features that raise the suspicion of these diseases and lead to the early control of the spread in our populations.


Successful Treatment of Legionnaires' Disease with Tigecycline in an Immunocompromised Man with a Legion of Antibiotic Allergies

Arget M, Kosar J, Suen B, Peermohamed S.

Internal Medicine/Infectious Disease, University of Saskatchewan College of Medicine, Saskatoon, CAN.

Cureus 2019 Apr;11(4):e4577.

Abstract: Legionella species are Gram-negative bacilli that are relatively rare causes of community-acquired pneumonia but can be associated with significant morbidity and mortality if unrecognized or improperly treated. Limited data exist regarding the use of tigecycline, a third generation glycylcycline, in the treatment of Legionnaires' disease. We present an immunocompromised patient with Legionnaires' disease and allergies to both fluoroquinolones and macrolides, which are first-line treatment options for Legionnaires' disease. He was successfully treated using tigecycline, a third generation glycylcycline, indicating that tigecycline may serve as a safe and effective alternative therapeutic option for treatment of Legionnaires' disease.


Extreme Rhabdomyolysis, Acute Renal Failure, and Protracted Ileus in a Case of Legionella Pneumonia

Laivier C, Bleuze MO, Hantson P, Devos J.

Department of Intensive Care, Centre Hospitalier de Mouscron, 7700 Mouscron, Belgium.

Case Rep Crit Care 2019 Jan;2019:3472627.

Abstract: A 53-year-old man developed a Legionella pneumophila pneumonia complicated by rhabdomyolysis, acute kidney injury, and protracted ileus. Risk factors were smoking and chronic alcoholism, but the patient had no history of previous abdominal surgery. Hemodialysis was required for a period of 5 weeks with a full renal recovery. Pneumonia required respiratory support but for a limited period of 6 days. The protracted course of the ileus led to explorative laparotomy despite negative computed tomography findings. No cause of mechanical obstruction was found at surgery and common etiologies of intestinal obstruction were excluded. Parenteral nutrition was needed for a total of 4 weeks, before recovery of intestinal motility. This case illustrates the apparent discrepancy between the pulmonary symptoms and the extrapulmonary manifestations that could be seen as a consequence of an exaggerated immune response.


Veno-Arterial Extracorporeal Membrane Oxygenation for Septic Cardiomyopathy Due to Legionella Pneumonia After Influenza Virus Infection

Asaki M, Masuda T, Miki Y.

Department of Emergency Medicine, Emergency and Critical Care Center, Fujieda Municipal General Hospital, Shizuoka, Japan.

Case Rep Crit Care 2018 Oct;2018:6973197.

Abstract: A 57-year-old man presented to the emergency department with fever and progressive altered level of consciousness of 5 days' duration. Three days before admission, influenza A was diagnosed at a clinic. On admission, his vital signs were unstable. Pneumonia was diagnosed through chest computed tomography, and urinary Legionella antigen test was positive. A diagnosis of septic shock due to Legionella and influenza pneumonia was made, and critical care management was initiated, including mechanical ventilation and vasopressors. However, tachycardia did not improve, left ventricular ejection fraction was 20%, and circulatory insufficiency progressed. Therefore, considering the involvement of septic cardiomyopathy and cardiogenic shock, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was initiated for circulation assistance on day 3 since admission. Tachycardia and myocardial dysfunction improved by day 8, and VA-ECMO was withdrawn. Subsequently, nutrition management and rehabilitation were performed, and the patient was transferred to a recovery hospital on day 108. VA-ECMO may be beneficial when concomitant with circulatory assistance in uncontrollable cases of septic cardiomyopathy using catecholamines and β-blockers. It may be necessary to adopt VA-ECMO at an appropriate time before the patient progresses to cardiopulmonary arrest.


Antibiotic Susceptibility of Legionella pneumophila Strains Isolated in England and Wales 2007-17

Wilson RE, Hill RLR, Chalker VJ, Mentasti M, Ready D.

Public Health England, Colindale, London, UK.

J Antimicrob Chemother 2018 Oct;73(10):2757-2761.

Abstract: Objectives: Antibiotic susceptibility of Legionella pneumophila is poorly understood, with treatment of Legionnaires' disease often based on empirical choice. The aim of this study was to determine the antibiotic susceptibility of L. pneumophila strains. Methods: Antibiotic susceptibility of 92 L. pneumophila strains isolated in England and Wales between 2007 and 2017 was determined using a microbroth dilution methodology for each agent tested. MICs and MBCs were determined and compared with published intracellular concentrations of each agent tested. Results: The MIC range of erythromycin was 0.06-1 mg/L, the MIC range of rifampicin was 0.0001 mg/L, the MIC range of ciprofloxacin was 0.004-0.25 mg/L and the MIC range of levofloxacin and moxifloxacin was 0.03-0.25 mg/L. The MBC range of erythromycin was 1-32 mg/L, but the MBC range of ciprofloxacin was the same as the MIC range. For levofloxacin and moxifloxacin, the MBC range was elevated by one dilution and two dilutions, respectively. Typically, intracellular bronchial secretion concentrations of erythromycin might be expected to reach a suitable level to exceed the MIC range; however, 91 of 92 (98.9%) isolates had an MBC below the expected intracellular concentrations, which indicated erythromycin may have variable efficacy. MIC and MBC values of ciprofloxacin, levofloxacin and moxifloxacin were below achievable intracellular levels within bronchial secretions. Comparison of the MIC/MBC correlation showed very little clustering for erythromycin, but strong clustering for levofloxacin and to a lesser extent ciprofloxacin. Conclusions: Use of the MIC/MBC linkage analysis seems an appropriate way forward for antimicrobial susceptibility testing and supports current guidance recommending levofloxacin for the treatment of Legionnaires' disease.


Legionella Pneumonia Complicated with Acquired Fanconi Syndrome

Koda R, Itoh R, Tsuchida M, Ohashi K, Iino N, Takada T, Narita I.

Department of Nephrology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan.

Intern Med 2018 Oct;57(20):2975-2980.

Abstract: Legionella pneumonia is occasionally accompanied by renal complications; however, the cause of this remains unknown. We herein report a 70-year-old Japanese man with Legionella pneumonia who presented with hyponatremia, hypophosphatemia, and hypouricemia. The levels of urinary β2-microglobulin and N-acetyl-β-D-glucosaminidase were remarkably high, indicating severe renal tubular damage. The presence of glycosuria and aminoaciduria as well as increased fractional excretion of uric acid and decreased tubular reabsorption of phosphate indicated that the patient's condition was complicated with Fanconi syndrome. After antimicrobial therapy, the electrolyte abnormalities and renal tubular damage were completely resolved.


A Novel Diagnostic Scoring System to Differentiate Between Legionella pneumophila Pneumonia and Streptococcus pneumoniae Pneumonia

Saraya T, Nunokawa H, Ohkuma K, Watanabe T, Sada M, Inoue M, Honda K, Oda M, Ogawa Y, Tamura M, Yokoyama T, Kurai D, Kimura H, Ishii H, Goto H, Takizawa H.

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

Intern Med 2018 Sep;57(17):2479-2487.

Abstract: Objective We investigated a novel diagnostic scoring system to differentiate Legionella pneumophila pneumonia from Streptococcus pneumoniae pneumonia. Methods We retrospectively reviewed the clinical data of 62 patients with L. pneumophila pneumonia (L-group) and 70 patients with S. pneumoniae pneumonia (S-group). Results The serum sodium (Na) levels tended to be lower according to the severity [age, dehydration, respiratory failure, orientation disturbance, low blood pressure (A-DROP)] score in the L-group. On a multivariate analysis, we found that four factors were independent predictive markers for inclusion in the L-group: relative bradycardia [hazard ratio (HR) 5.177, 95% confidence interval (CI): 1.072-24.993, p=0.041], lactate dehydrogenase (LDH) levels ≥292 IU/L (HR 6.804, 95% CI: 1.629-28.416, p=0.009), C-reactive protein (CRP) levels ≥21 mg/dL (HR 28.073, 95% CI: 5.654-139.462, p<0.001), and Na levels ≤137 meq/L (HR 5.828, 95% CI: 1.411-24.065, p=0.015). Furthermore, a total score [ranging from 0 to 4, the sum of the points for each factor (0 or 1)] ≥3 points indicated a higher probability of inclusion in the L-group than in the S-group. The diagnostic accuracy of a total score of 3 had a sensitivity of 36.3%, specificity of 100%, and area under the curve of 0.682 (95% CI: 0.558-0.806, p=0.004), and that of a total score of 4 had a sensitivity 27.4%, specificity of 98.2%, and area under the curve (AUC) of 0.627 (95% CI: 0.501-0.754, p=0.045). The diagnostic accuracy had low sensitivity but high specificity. Conclusions We found four markers that might be useful for differentiating L-group from S-group and created a novel diagnostic scoring system.


Presence of Legionella Spp. in Human Dental Plaque

Tesauro M, Petrelli F, Lizioli A, Pregliasco F, Masia C, Cossellu G, Farronato G, Consonni M, Sisto F.

Department of Biomedical Surgical and Dental Sciences, University of Milan, Italy.

Ann Ig 2018 Sep-Oct;30(5):387-390.

Abstract: Aims: The aim of this research is to verify the presence of Legionella in human dental plaque. Methods: 65 adult patients not treated with systemic or local antibiotics at least 2 months before the time of sample collection were enrolled for plaque collection between September 2015 and December 2016. A brief questionnaire about lifestyle and health risks was administered. Legionella spp. detection has been executed by semi- nested PCR. Results: 8 out of 65 plaque samples (12.3%) were positive for Legionella spp. As regards health risks and lifestyle aspects, no relevant difference was observed between patients involved in our study, except for two positive patients who have reported a COPD ongoing and a pneumonia in the past. Conclusions: This study represents a step forward in the knowledge of reservoirs of the microorganism and richness of oral microbiota.


Disseminated Extrapulmonary Legionella pneumophila Infection Presenting with Panniculitis: Case Report and Literature Review

Chitasombat MN, Ratchatanawin N, Visessiri Y.

Division of Infectious Disease, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

BMC Infect Dis 2018 Sep;18(1):467.

Abstract: Background: Legionellosis is a well-known cause of pneumonia. Primary cutaneous and subcutaneous infection caused by Legionella pneumophila is rare and the diagnosis is challenging. Case presentation: A 38-year-old Thai woman with systemic lupus erythematosus and myasthenia gravis treated with prednisolone and azathioprine presented to our hospital with low-grade fever, diarrhea, and indurated skin lesions on both thighs. Initial examination showed plaques on both inner thighs. Magnetic resonance imaging showed myositis and swelling of the skin and subcutaneous tissue. Diagnosis of panniculitis due to L. pneumophila was carried out by histopathology, Gram stain, and 16S rRNA gene sequencing method of tissue biopsy from multiple sites on both thighs. Myocarditis was diagnosed by echocardiography. The final diagnosis was disseminated extrapulmonary legionellosis. Treatment comprised intravenous azithromycin for 3 weeks and the skin lesions, myositis and myocarditis resolved. Oral azithromycin and ciprofloxacin were continued for 3 months to ensure eradication of the organism. The patient's overall condition improved. Conclusions: To our knowledge, we report the first case of L. pneumophila infection manifesting with panniculitis, possible myositis, and myocarditis in the absence of pneumonia. The diagnosis of extrapulmonary Legionella infection is difficult, especially in the absence of pneumonia. A high index of suspicion and appropriate culture with special media or molecular testing are required. Initiation of appropriate treatment is critical because delaying therapy was associated with progressive infection in our patient.


Immunosuppressive Treatment and Its Effect on the Occurrence of Pneumocystis jiroveci, Mycoplasma pneumoniae, Chlamydophila pnemoniae, and Legionella pneumophila Infections/Colonizations among Lung Transplant Recipients

Wojarski J, Ochman M, Latos M, Biniszkiewicz P, Karolak W, Woźniak-Grygiel E, Maruszewski M, Urlik M, Mędrala W, Kułaczkowska Z, Pyrc K, Żegleń S.

Department of Cardiac, Vascular and Endovascular Surgery and Transplantology, Medical University of Silesia in Katowice, Silesian Center for Heart Diseases, Zabrze, Poland.

Transplant Proc 2018 Sep;50(7):2053-2058.

Abstract: Background: The aim of the study was to assess the frequency of infections caused by Pneumocystis jiroveci, Chlamydophila pneumoniae, Legionella pneumophila, and Mycoplasma pneumoniae among lung transplant recipients in the context of immunosuppression. Methods: The study group consisted of 94 patients (37 women and 57 men; mean age 42.03 years) transplanted between 2009 and 2016 at the Silesia Center for Heart Diseases (SCCS). Immunosuppressive treatment (induction and maintenance therapy) was assessed. The immunofluorescence methods were used to detect the P. jiroveci, L. pneumophila, C. pneumoniae, and M. pneumoniae antigens in samples obtained from the respiratory tract. Results: Thirty-two of 94 graft recipients developed atypical or opportunistic infection. The median time of its occurrence was 178 days after transplantation. P. jiroveci was responsible for 84.38% of first infections. Five patients developed infection with P. jiroveci and C. pneumoniae. None of the infections occurred during induction of immunosuppression. An opportunistic or atypical infection developed in 19.35% of the patients treated with a tacrolimus-based regimen, and in 43.33% of patients on a cyclosporine-based regimen. Conclusion: Infection with P. jiroveci is a recognized problem after lung transplantation and should be monitored. The percentage of infected patients is higher in patients treated with a cyclosporine-based regimen in comparison to those treated with tacrolimus.


MAIT Cells Protect Against Pulmonary Legionella longbeachae Infection

Wang H, D'Souza C, Lim XY, Kostenko L, Pediongco TJ, Eckle SBG, Meehan BS, Shi M, Wang N, Li S, Liu L, Mak JYW, Fairlie DP, Iwakura Y, Gunnersen JM, Stent AW, Godfrey DI, Rossjohn J, Westall GP, Kjer-Nielsen L, Strugnell RA, McCluskey J, Corbett AJ, Hinks TSC, Chen Z.

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia.

Nat Commun 2018 Aug;9(1):3350.

Abstract: Mucosal associated invariant T (MAIT) cells recognise conserved microbial metabolites from riboflavin synthesis. Striking evolutionary conservation and pulmonary abundance implicate them in antibacterial host defence, yet their functions in protection against clinically important pathogens are unknown. Here we show that mouse Legionella longbeachae infection induces MR1-dependent MAIT cell activation and rapid pulmonary accumulation of MAIT cells associated with immune protection detectable in immunocompetent host animals. MAIT cell protection is more evident in mice lacking CD4+ cells, and adoptive transfer of MAIT cells rescues immunodeficient Rag2-/-γC-/- mice from lethal infection. Protection is dependent on MR1, IFN-γ and GM-CSF, but not IL-17A, TNF or perforin, and enhanced protection is detected earlier after infection of mice antigen-primed to boost MAIT cell numbers before infection. Our findings define a function for MAIT cells in protection against a major human pathogen and indicate a potential role for vaccination to enhance MAIT cell immunity.


In Vitro Activity of Various Antibiotics Against Clinical Strains of Legionella Species Isolated in Japan

Miyashita N, Kobayashi I, Higa F, Aoki Y, Kikuchi T, Seki M, Tateda K, Maki N, Uchino K, Ogasawara K, Kurachi S, Ishikawa T, Ishimura Y, Kanesaka I, Kiyota H, Watanabe A.

Department of Internal Medicine 1, Kawasaki Medical School, Okayama, Japan.

J Infect Chemother 2018 May;24(5):325-329.

Abstract: The activities of various antibiotics against 58 clinical isolates of Legionella species were evaluated using two methods, extracellular activity (minimum inhibitory concentration [MIC]) and intracellular activity. Susceptibility testing was performed using BSYEα agar. The minimum extracellular concentration inhibiting intracellular multiplication (MIEC) was determined using a human monocyte-derived cell line, THP-1. The most potent drugs in terms of MICs against clinical isolates were levofloxacin, garenoxacin, and rifampicin with MIC90 values of 0.015 μg/ml. The activities of ciprofloxacin, pazufloxacin, moxifloxacin, clarithromycin, and azithromycin were slightly higher than those of levofloxacin, garenoxacin, and rifampicin with an MIC90 of 0.03-0.06 μg/ml. Minocycline showed the highest activity, with an MIC90 of 1 μg/ml. No resistance against the antibiotics tested was detected. No difference was detected in the MIC distributions of the antibiotics tested between L. pneumophila serogroup 1 and L. pneumophila non-serogroup 1. The MIECs of ciprofloxacin, pazufloxacin, levofloxacin, moxifloxacin, garenoxacin, clarithromycin, and azithromycin were almost the same as their MICs, with MIEC90 values of 0.015-0.06 μg/ml, although the MIEC of minocycline was relatively lower and that of rifampicin was higher than their respective MICs. No difference was detected in the MIEC distributions of the antibiotics tested between L. pneumophila serogroup 1 and L. pneumophila non-serogroup 1. The ratios of MIEC:MIC for rifampicin (8) and pazufloxacin (2) were higher than those for levofloxacin (1), ciprofloxacin (1), moxifloxacin (1), garenoxacin (1), clarithromycin (1), and azithromycin (1). Our study showed that quinolones and macrolides had potent antimicrobial activity against both extracellular and intracellular Legionella species. The present data suggested the possible efficacy of these drugs in treatment of Legionella infections.


Legionella feeleii: An Unusual Organism Associated with Cutaneous Infection in an Immunocompromised Patient

Verykiou S, Goodhead C, Parry G, Meggitt S.

Dermatology Department, Royal Victoria Infirmary, Newcastle upon Tyne, UK.

Clin Exp Dermatol Apr 2018;43(3):300-302.

Abstract: We report a 23-year-old immunocompromised woman who, following cardiac transplantation, presented with an unusual cutaneous eruption. She developed a widespread pustular rash, systemic symptoms and a high temperature with raised inflammatory markers. The diagnosis was reached when a skin biopsy was cultured onto Legionella agar (buffered charcoal yeast extract) and Legionella feeleii was isolated. The patient was treated with 6 weeks of moxifloxacin and her cutaneous lesions gradually resolved. Cutaneous Legionella infections are uncommon and usually affect immunocompromised patients.


Hepatic Legionella pneumophila Infection in an Infant with Severe Combined Immunodeficiency

Lapidot R, Alawdah L, Köhler JR, Paulson V, Levy O.

Division of Pediatric Infectious Diseases, Boston Medical Center, Boston, MA, USA.

Pediatr Infect Dis J 2018 Apr;37(4):356-358.

Abstract: Rare cases of extrapulmonary involvement in Legionella spp. infections have been described, mostly in immunocompromised adults. We report a case of a 2-month old male with reticular dysgenesis variant of severe combined immune deficiency with multiple liver lesions. Core-needle biopsies of one liver lesion demonstrated Gram-negative bacilli and a broad-spectrum polymerase chain reaction assay detected Legionella pneumophila.


Study of the Radiologic Features of Legionnaires' Disease with Mediastinal Adenopathy: Legionella or Lymphoma?

Cunha BA, Varantsova A, Jimada I.

Infectious Disease Division, NYU Winthrop Hospital, Mineola, NY, USA.

Eur J Clin Microbiol Infect Dis 2018 Mar;37(3):463-468.

Abstract: An index case of Legionnaires's disease with mediastinal adenopathy prompted us to review our recent experience with Legionnaires' disease to determine the incidence of mediastinal adenopathy of this finding in Legionnaires' disease. We reviewed the radiographic findings of 90 hospitalized adults with Legionnaires' disease from 2015 to 2017. Excluded were 11 patients with mediastinal adenopathy due to non-Legionnaires' disease causes, e.g., lymphoma. Thirty-seven of the remaining patients had both chest films and chest computed tomography (CT) scans. Of the 37 Legionnaires' disease cases, 13/37 (35%) had mediastinal adenopathy and 8/27 (24%) also had unilateral hilar adenopathy. These chest CT findings were not seen on chest films. Chest CT scans are needed to detect mediastinal adenopathy in Legionnaires' disease. Mediastinal adenopathy may be due to Legionnaires' disease or a malignancy. Some findings in Legionnaires' disease are also present in mediastinal adenopathy due to lymphomas, e.g., highly elevated erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), and ferritin. Hospitalized adults with Legionnaires' disease and mediastinal adenopathy should have serial chest CT scans to monitor resolution of the mediastinal adenopathy. In hospitalized adults with otherwise unexplained persistent mediastinal adenopathy, they should be considered as being due to another etiology, e.g., lymphoma, until proven otherwise.


Legionella Pneumonia Due to non-Legionella Pneumophila Serogroup 1: Usefulness of the Six-Point Scoring System

Ito A, Ishida T, Washio Y, Yamazaki A, Tachibana H.

Department of Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central Hospital, Okayama, Japan.

BMC Pulm Med 2017 Dec;17(1):211.

Abstract: Background: Because of a limited number of reports, we aimed to investigate the clinical characteristics of patients with Legionella pneumonia due to non-Legionella pneumophila serogroup 1 and the diagnostic usefulness of the six-point scoring system for such patients compared with patients with pneumonia caused by L. pneumophila serogroup 1. Methods: We retrospectively analysed patients diagnosed with Legionella pneumonia due to non-L. pneumophila serogroup 1 between March 2001 and June 2016. We examined the clinical characteristics, including symptoms, laboratory findings, radiologic findings, pneumonia severity, initial treatment and prognosis. We also calculated scores using the six-point scoring system in these patients. Furthermore, we compared the clinical characteristics and six-point scores between non-L. pneumophila serogroup 1 patients and L. pneumophila serogroup 1 patients among hospitalized community-acquired pneumonia patients enrolled prospectively between October 2010 and July 2016. Results: Eleven patients had pneumonia due to non-L. pneumophila serogroup 1; their median age was 66 years and 8 patients (72.7%) were male. The most common pathogen was L. pneumophila serogroup 3 (6/11), followed by L. pneumophila serogroup 9 (3/11), L. pneumophila serogroup 6 (1/11) and L. longbeachae (1/11). Non-specific symptoms, such as fever and cough, were common. Six patients (54.5%) had liver enzyme elevation, but no patient developed hyponatremia at <130 mEq/L. Nine patients (81.8%) showed lobar pneumonia and 7 patients (63.6%) manifested with consolidation and ground-glass opacity. Patients with mild to moderate severity comprised 10 (90.9%) by CURB-65 and 5 (45.5%) by the Pneumonia Severity Index. Of all patients, 4 were admitted to the intensive care unit and 3 died despite appropriate empiric therapy. The clinical characteristics were not significantly different between non-L. pneumophila serogroup 1 patients and L. pneumophila serogroup 1 patients (n=23). At a cut-off value of ≥2 points, the sensitivity of the six-point scoring system was 54.5% (6/11) for non-L. pneumophila serogroup 1 patients and 95.7% (22/23) for L. pneumophila serogroup 1 patients. Conclusions: Cases of non-L. pneumophila serogroup 1 pneumonia varied in severity from mild to severe and the clinical characteristics were often non-specific. The six-point scoring system was not useful in predicting such Legionella pneumonia cases.


Low Antibodies Titer and Serological Cross-Reaction Between Coxiella burnetii and Legionella pneumophila Challenge the Diagnosis of Mediastinitis, an Emerging Q Fever Clinical Entity

Edouard S, Million M, Casalta JP, Collart F, Amphoux B, Raoult D.

Aix Marseille Univ, CNRS, Marseille, France.

Infection 2017 Dec;45(6):911-915.

Abstract: Background: Coxiella burnetii is an intracellular and fastidious bacterium responsible of acute and persistent Q fever infection. Endocarditis and vascular infections are the most common serious complications of acute Q fever. Case report: We report the case of a 63-year-old man that presented a mediastinitis associated with a prosthetic vascular infection. Serological cross-reaction was observed between Coxiella burnetii, the agent of Q fever, and Legionella pneumophila with higher antibodies titer for L. pneumophila (IgG=1:512) than for C. burnetii (phase I IgG=1:400). We performed western blot with cross-adsorption that supports the diagnosis of C. burnetii infection. Two weeks later, a positive qPCR and culture for C. burnetii on swab taken from the mediastinal cutaneous fistula confirmed the definitive microbiological diagnosis of Q fever mediastinitis. Conclusion: Cross-reactivity between C. burnetii and Legionella spp. has long been known and should be considered in patients with persistent infections. It is important to establish the definite diagnosis because the antibiotic treatment regimens and duration are significantly different. To the best of our knowledge, we reported here the first case of mediastinitis associated to C. burnetii and we diagnosed this persistent infection despite low anti-C. burnetii phase I IgG levels.


Innate Immune Surveillance in the Central Nervous System Following Legionella pneumophila Infection

Laganà P, Soraci L, Gambuzza ME, Mancuso G, Delia SA.

Regional Reference Laboratory of Clinical and Environmental Surveillance of Legionellosis, Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.

CNS Neurol Disord Drug Targets 2017;16(10):1080-1089.

Abstract: Background & objective: The innate immune response is a common occurrence in many neuroinflammatory diseases. Central Nervous System (CNS) resident immune cells are able to detect and react to infections and sterile trauma. Peripheral immune cell migration into CNS is regulated by the blood-brain barrier, although peripheral immune cells can invade CNS through meninges, choroid plexus, perivascular spaces, and cerebrospinal fluid. Consequently, in the brain, immune reactions can be mediated by both resident and peripheral immune cells. Both in the periphery and within the CNS, innate immune response is regulated by a wide array of pattern recognition receptors, including Toll-like, scavenger, Retinoic Acid-inducible Gene-1 like, and nucleotide-binding oligomerization domains-like responsible for inflammasome formation. Inflammasome pathway activation induces pyroptosis, a highly inflammatory cell death pattern that occurs to remove intracellular pathogens. Legionella pneumophila is an intracellular microorganism responsible for Legionnaires' disease, a lung infection always associated to neurological dysfunctions. Recent studies have been shown that Toll-like receptors, nucleotide-binding oligomerization domains-like receptors, and RIG-1 like, are activated by L. pneumophila. This flagellated bacterium is able to replicate in phagocytic cells, including macrophages and microglia, responding by activating inflammasome pathways that may be the cause of CNS dysfunction detected in several infected patients.

Conclusion: The aim of this review is to bring together the latest findings concerning L. pneumophila infection and innate immune host cell responses. A deeper knowledge of these processes could allow the use of immunomodulatory compounds able to counteract CNS involvement following L. pneumophila infection.


Legionnaires' Disease Complicated with Rhabdomyolysis and Acute Kidney Injury in an AIDS Patient

Seegobin K, Maharaj S, Baldeo C, Downes JP, Reddy P.

Department of Internal Medicine, University of Florida College of Medicine, Jacksonville, FL 32209, USA.

Case Rep Infect Dis 2017;2017:8051096.

Abstract: Objective: To present a case of an uncommon triad of Legionella pneumonia, rhabdomyolysis, and renal failure, with review of the relevant literature. Case: A 51-year-old with a history of human immunodeficiency virus (HIV), chronic obstructive pulmonary disease (COPD), and hypertension presented with fever, cough, and shortness of breath over four days. Chest X-ray showed consolidation in left lower lung field; urine was positive for Legionella antigen and myoglobin; creatine kinase was 51092U/L; creatine was 6.9 mg/dL, and his CD4 count was 41 cells/ul. He was managed with azithromycin and levofloxacin and further required dialysis and ventilatory support in the intensive care unit due to renal failure and respiratory failure. He responded well to the treatment and made a complete recovery. Legionella pneumophila infection is a recognized but rare cause of rhabdomyolysis with high morbidity and mortality when there is extrapulmonary involvement. Early diagnosis and appropriate treatment is essential to improve outcomes. Conclusion: Physicians should consider Legionella pneumonia in patients with rhabdomyolysis, renal failure, and respiratory symptoms. Early diagnosis and treatment have been shown to have good clinical response. Timely intensive care management, together with early and judicious use of dialysis in patients complicated with rhabdomyolysis and renal failure, may lead to good outcomes.


Clinical Presentation of Legionella Pneumonia: Evaluation of Clinical Scoring Systems and Therapeutic Efficacy

Miyashita N, Higa F, Aoki Y, Kikuchi T, Seki M, Tateda K, Maki N, Uchino K, Ogasawara K, Kiyota H, Watanabe A.

Department of Internal Medicine 1, Kawasaki Medical School, Okayama, Japan.

J Infect Chemother 2017 Nov;23(11):727-732.

Abstract: To evaluate scoring systems to predict Legionella pneumonia and therapeutic efficacy against Legionella pneumonia, the Japanese Society of Chemotherapy Legionella committee has collected data on cases of Legionella pneumonia from throughout Japan. We analyzed 176 patients with Legionella pneumonia and compared them with 217 patients with Streptococcus pneumoniae pneumonia and 202 patients with Mycoplasma pneumoniae pneumonia. We evaluated four scoring systems, the Winthrop-University Hospital score, Community-Based Pneumonia Incidence Study Group score, and Japan Respiratory Society score, but they demonstrated limited sensitivity and specificity for predicting Legionella pneumonia. Using six clinical and laboratory parameters (high fever, high C-reactive protein, high lactate dehydrogenase, thrombocytopenia, hyponatremia, and unproductive cough) reported by Fiumefreddo and colleagues, only 6% had Legionnella pneumonia when less than 2 parameters were present. The efficacy rates of antibiotics at the time of termination were 94.6% for intravenous antibiotics, including ciprofloxacin and pazufloxacin, and 95.5% for oral antibiotics, including ciprofloxacin, levofloxacin, garenoxacin, moxifloxacin, and clarithromycin. Our results suggested that the previously reported clinical scoring systems to predict Legionella pneumonia are not useful, but 6 simple diagnostic score accurately ruled out Legionella pneumonia, which may help to optimize initial empiric therapy. Quinolones and clarithromycin still showed good clinical efficacy against Legionella pneumonia.


Levofloxacin Versus Azithromycin for Treating Legionella Pneumonia: A Propensity Score Analysis

Garcia-Vidal C, Sanchez-Rodriguez I, Simonetti AF, Burgos J, Viasus D, Martin MT, Falco V, Carratalà J.

Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, Spain; REIPI, Instituto de Salud Carlos III, Madrid, Spain.

Clin Microbiol Infect 2017 Sep;23(9):653-658.

Abstract: Objectives: Concerns have arisen regarding the equivalence of levofloxacin and some macrolides for treating community-acquired legionella pneumonia (LP). We aimed to compare the outcomes of current patients with LP treated with levofloxacin, azithromycin and clarithromycin. Methods: Observational retrospective multicentre study of consecutive patients with LP requiring hospitalization (2000-2014) conducted in two hospitals. The primary outcome assessed was 30-day mortality. To control for confounding, therapy was assessed by multivariate analysis. Results: We documented 446 patients with LP, of which 175 were treated with levofloxacin, 177 with azithromycin and 58 with clarithromycin. No significant differences in time to defervescence (2 (interquartile range (IQR) 1-4) versus 2 (IQR 1-3) days; p 0.453), time to achieve clinical stability (3 (2-5) versus 3 (2-5) days; p 0.486), length of intravenous therapy (3 (2-5.25) versus 4 (3-6) days; p 0.058) and length of hospital stay (7 (5-10) versus 6 (5-9) days; p 0.088) were found between patients treated with levofloxacin and those treated with azithromycin. Patients treated with clarithromycin had longer intravenous antibiotic treatment (3 (2-5.25) versus 5 (3-6.25) days; p 0.002) and longer hospital stay (7 (5-10) versus 9 (7-14) days; p 0.043) compared with those treated with levofloxacin. The overall mortality was 4.3% (19 patients). Neither univariate nor multivariate analysis showed a significant association of levofloxacin versus azithromycin on mortality (4 (2.3%) versus 9 (5.1%) deaths; p 0.164). The results did not change after incorporation of the propensity score into the models. Conclusions: In our study, no significant differences in most outcomes were found between patients treated with levofloxacin and those treated with azithromycin. Due to the small number of deaths, results regarding mortality should be interpreted with caution.


Septic Arthritis Due to Legionella Cincinnatiensis: Case Report and Review of the Literature

Banderet F, Blaich A, Soleman E, Gaia V, Osthoff M.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.

Infection 2017 Aug;45(4):551-555.

Abstract: Legionella spp. are an important cause of pulmonary and rarely extrapulmonary infections. L. cincinnatiensis has only been implicated in five cases to date. We herein report the first case of L. cincinnatiensis septic arthritis in a 90-year old lady with a past medical history of chronic kidney disease. She developed septic arthritis of her left wrist after having received intraarticular corticosteroid injections and oral corticosteroids administered for presumed chondrocalcinosis. Appropriate antimicrobial treatment of L. cincinnatiensis septic arthritis was delayed until identification of this organism in joint biopsies by broad-range bacterial PCR targeting the 16S rRNA gene with subsequent rDNA sequence analysis and by culture on special media. Reviewing all reported cases of septic arthritis caused by Legionella spp. other than L. cincinnatiensis it is notable that diagnosis was established by PCR in the majority of cases and only subsequently confirmed by special culture. Although most patients were immunosuppressed, outcome was favourable. Treatment consisted of a fluoroquinolone alone or in combination with rifampicin or a macrolide. Our case highlights the need for a high index of suspicion for infections with unusual/fastidious organisms when symptoms are suggestive of septic arthritis, but conventional methods fail to identify a causative organism.


Early Radiographic and Tomographic Manifestations of Legionnaires' Disease

Poirier R, Rodrigue J, Villeneuve J, Lacasse Y.

Centre de recherche, Centre de pneumologie, Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, Québec City, Québec, Canada.

Can Assoc Radiol J 2017 Aug;68(3):328-333

Abstract: Purpose: Legionnaires' disease (LD) may occur sporadically or in the course of outbreaks, where the typical radiological manifestations of the disease may better be delineated. We took advantage of a rare community-based epidemic of LD (181 patients) that occurred in 2012 in Quebec City, Canada, to describe the radiographic features of LD and compare the its tomographic presentation with that of community-acquired pneumonia caused by common bacteria other than Legionella pneumophila. Methods: From the 181 individuals affected in the outbreak, we obtained the chest radiographs of 159 individuals (mean 63±15 years of age) for detailed analysis; 33 patients had a computed tomography (CT) scan performed during the course of their illness. In a case-control study, we compared the CT scans of patients with LD with those of patients who had received a diagnosis of community-acquired pneumonia caused by a pathogen other than Legionella and confirmed by chest CT scan. Results: Overall, LD most often presented as an airspace consolidation involving 1 of the lower lobes. Pleural effusion and mediastinal adenopathies were apparent only in a minority, whereas no pneumothorax or cavitation was noted. We did not find any significant difference in chest CT scan findings in patients with LD vs those with community-acquired pneumonia from other bacterial origin. No radiological finding was clearly associated with an increased risk of intensive care unit admission or mortality. Conclusions: The early radiographic and tomographic manifestations of LD are nonspecific and similar to those found in community-acquired pneumonia from other bacterial origin.


Macrolide Therapy for Community-Acquired Pneumonia Due to Atypical Pathogens: Outcome Assessment at an Early Time Point

File TM Jr, Eckburg PB, Talbot GH, Llorens L, Friedland HD.

Summa Health System, Akron, OH, USA.

Int J Antimicrob Agents 2017 Aug;50(2):247-251.

Abstract: Background: Therapy directed against atypical pathogens in patients with community-acquired pneumonia (CAP) is often recommended. This post-hoc analysis evaluated the effect of addition of a macrolide to ceftaroline fosamil or ceftriaxone treatment in atypical CAP. Methods: Two phase 3, double-blind, comparative safety and efficacy studies of ceftaroline fosamil vs. ceftriaxone, FOCUS 1 and FOCUS 2, enrolled adults with CAP. Only FOCUS 1 included 24-h adjunctive clarithromycin therapy for all patients on day 1. Day 4 and test-of-cure (TOC) outcomes were compared for adjunctive vs. no adjunctive therapy. Results: Of 1240 enrolled patients, 130 patients with CAP due to atypical pathogens alone were included (FOCUS 1, n=64; FOCUS 2, n=66). Among patients infected with Mycoplasma pneumoniae and/or Chlamydophila pneumoniae alone, a higher clinical response rate was observed with clarithromycin plus ceftaroline fosamil or ceftriaxone compared with treatment without additional clarithromycin at day 4 [38/49 (77.6%; FOCUS 1) vs. 24/43 (55.8%; FOCUS 2)], but not at the TOC assessment [42/49 (85.7%; FOCUS 1) vs. 41/43 (95.3%; FOCUS 2)]. In patients infected with Legionella pneumophila alone, a higher clinical response rate with adjunctive clarithromycin therapy was observed at the TOC assessment alone [12/12 (100%; FOCUS 1) vs. 14/19 (73.7%; FOCUS 2)]. The unadjusted odds ratio of a favourable clinical response at day 4 with adjunctive clarithromycin vs. no adjunctive clarithromycin was 2.4 (95% confidence interval 1.1-5.1;P=0.0299) for all pathogens combined. Conclusions: These results suggest that empirical antibiotic therapy against atypical pathogens may improve early clinical response rate. This hypothesis is best evaluated in a prospective trial.


Legionella pneumophila Pneumonia in Two Infants Treated with Adrenocorticotropic Hormone

Shachor-Meyouhas Y, Ravid S, Hanna S, Yaacoby-Bianu K, Kassis I.

Pediatric Infectious Diseases Unit, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.

J Pediatr 2017 Jul;186:186-188.

Abstract: Patients with infantile spasms, an intractable epileptic disorder, often are treated with adrenocorticotropic hormone. Legionella pneumophila is a rare cause of pneumonia in children. We describe 2 infants with Legionella pneumonia whose infection occurred within 1 month after starting adrenocorticotropic hormone.


Outcome and Management of Refractory Respiratory Failure with Timely Extracorporeal Membrane Oxygenation: Single-Center Experience with Legionella Pneumonia

Roncon-Albuquerque R Jr, Vilares-Morgado R, van der Heijden GJ, Ferreira-Coimbra J, Mergulhão P, Paiva JA.

Department of Emergency and Intensive Care Medicine, Centro Hospitalar S. João, Porto, Portugal.

J Intensive Care Med 2019 Apr;34(4):344-350.

Abstract: Objective: To analyze the management and outcome of patients with refractory respiratory failure complicating severe Legionella pneumonia rescued with extracorporeal membrane oxygenation (ECMO) in our Center. Design and setting: Observational study of patients with refractory respiratory failure treated with ECMO in Hospital S. João (Porto, Portugal), between November 2009 and September 2016. Participants: A total of 112 patients rescued with ECMO, of which 14 had Legionella pneumonia. Results: Patients with Legionella pneumonia were slightly older than patients with acute respiratory failure of other etiologies (51 [48-56] vs 45 [35-54]), but with no significant differences in acute respiratory failure severity between groups: Pao2/Fio2 ratio 67 (60-75) versus 69 (55-85) and Respiratory Extracorporeal Membrane Oxygenation Survival Prediction score 4 (1-5) versus 2 (-1-4), respectively. Legionella pneumonia was associated with earlier ECMO initiation (days of invasive mechanical ventilation [IMV] before ECMO: 2.0 [1.0-4.0] vs 5.0 [2.0-9.5]). After IMV adjustment to "lung rest" settings, this group presented higher respiratory system (RS) static compliance (28.7 [18.8-37.4] vs 16.0 [10.0-20.8] mL/cmH2O) but required higher ECMO support (blood flow 5.0 [4.3-5.4] vs 4.2 [3.6-4.8]). Patients with Legionella pneumonia had shorter IMV (16 [14-23] vs 27 [20-42] days) and lower incidence of intensive care unit nosocomial infections (35.7% vs 64.3%), with a trend to higher hospital survival (85.7% vs 62.2%; P = .13). Conclusion: In Legionella pneumonia complicated by refractory respiratory failure, ECMO support allowed patient stabilization under lung protective ventilation and high survival rates. Timely ECMO referral should be considered for Legionella pneumonia failing conventional treatment.


Legionella Pneumonia Associated with Severe Acute Respiratory Distress Syndrome and Diffuse Alveolar Hemorrhage - A Rare Association

Kashif M, Patel R, Bajantri B, Diaz-Fuentes G.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Bronx Lebanon Hospital Center, Affiliated with Icahn School of Medicine at Mount Sinai, USA.

Respir Med Case Rep, 2017 Mar;21:7-11.

Abstract: Legionella pneumophila is a common, usually underreported and undiagnosed cause of community acquired pneumonia which can lead to significant morbidity and mortality. Diffuse alveolar hemorrhage rarely has been associated with legionella infection. We present a 61-year-old man with hypertension, diabetes mellitus and obesity admitted with severe acute respiratory distress syndrome. He was found to have Legionella pneumonia with associated diffuse alveolar hemorrhage diagnosed with bronchoscopic sequential bronchoalveolar lavage. He was successfully managed with antibiotics, lung protective strategies and intravenous pulse dose steroids. This patient highlights the unusual association ofinfection and diffuse alveolar hemorrhage. Additionally, the case re-enforces the need for early and aggressive evaluation and management of patients presenting with pneumonia and progressive hypoxia despite adequate treatment.


Legionnaire's Disease and Its Mimics: A Clinical Perspective

Cunha BA, Cunha CB.

Infectious Disease Division, Winthrop-University Hospital, Mineola, NY, USA.

Infect Dis Clin North Am 2017 Mar;31(1):95-109.

Abstract: Whenever the cardinal manifestations of a disorder occur in similar disorders, there is potential for a disease mimic. Legionnaire's disease has protean manifestations and has the potential to mimic or be mimicked by other community acquired pneumonias (CAPs). In CAPs caused by other than Legionella species, the more characteristic features in common with legionnaire's disease the more difficult the diagnostic conundrum. In hospitalized adults with CAP, legionnaire's disease may mimic influenza or other viral pneumonias. Of the bacterial causes of CAP, psittacosis and Q fever, but not tularemia, are frequent mimics of legionnaire's disease.


Legionnaire's Disease: A Clinical Diagnostic Approach

Cunha BA, Cunha CB.

Infectious Disease Division, Winthrop-University Hospital, Mineola, NY, USA.

Infect Dis Clin North Am 2017 Mar;31(1):81-93.

Abstract: Legionnaire's disease is a nonzoonotic atypical pneumonia caused by Legionella sp that occurs sporadically or in outbreaks. Legionnaire's disease pneumonia is accompanied by several extrapulmonary clinical and laboratory findings. Rather than testing all pneumonias for Legionnaire's disease, the clinical challenge is to recognize the diagnostic significance of Legionnaire's disease. The pretest probability of Legionnaire's disease is increased if several characteristic extrapulmonary findings are present. Similarly, if certain key findings are absent, Legionnaire's disease may be eliminated from further diagnostic consideration. If characteristic clinical findings are present, then specific tests should be ordered to confirm or rule out Legionnaire's disease.


Legionnaire's Disease: Cardiac Manifestations

Brusch JL.

Medical Department, Cambridge Health Alliance, Cambridge, MA, USA.

Infect Dis Clin North Am 2017 Mar;31(1):69-80.

Abstract: Most cardiac infections with Legionella are secondary to bacteremias arising from a pulmonary focus. Other possible sites of origin are infected sternotomy wounds or equipment contaminated by Legionella spp. Legionella endocarditis is truly a "stealth" infection, with almost no hallmarks of bacterial endocarditis. The key step in making the diagnosis of Legionella endocarditis is for the physician to be aware of the clinical causes of culture-negative infective endocarditis and to include Legionella cardiac involvement in this differential. Many times the issue of endocarditis arises only on examination of resected valvular material.


Antimicrobial Therapy for Legionnaire's Disease: Antibiotic Stewardship Implications

Cunha CB, Cunha BA.

Division of Infectious Disease, Rhode Island Hospital, The Miriam Hospital, Brown University Alpert School of Medicine, Providence, RI, USA.

Infect Dis Clin North Am 2017 Mar;31(1):179-191.

Abstract: Legionnaire's disease is a common cause of community-acquired pneumonia (CAP). Although no single clinical feature is diagnostic, if characteristic extrapulmonary findings are present a presumptive clinical syndromic diagnosis is possible. Depending on geographic location, season, and physician awareness, Legionnaire's disease may be included in the differential diagnosis of CAP. Some antibiotics effective against Legionella sp are also effective in treating the typical bacterial causes of CAP. From an antimicrobial stewardship program (ASP) perspective, monotherapy is preferred to double-drug therapy. From an ASP and pharmacoeconomic standpoint, monotherapy with doxycycline or a respiratory quinolone provides optimal cost-effective therapy.


Legionnaire's Disease and Influenza

Magira EE, Zakynthinos S.

1st Department of Critical Care Medicine, Evangelismos General Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Infect Dis Clin North Am 2017 Mar;31(1):137-153.

Abstract: Legionella pneumophila and influenza types A and B viruses can cause either community-acquired pneumonia with respiratory failure, or Legionella infection could attribute to influenza infection with potentially fatal prognosis. Copathogenesis between pandemic influenza and bacteria is characterized by complex interactions between coinfecting pathogens and the host. Understanding the underlying reason of the emersion of the secondary bacterial infection during an influenza infection is challenging. The dual infection has an impact on viral control and may delay viral clearance. Effective vaccines and antiviral therapy are crucial to increase resistance toward influenza, decrease the prevalence of influenza, and possibly interrupt the potential secondary bacterial infections.


Legionnaire's Disease in Compromised Hosts

Lanternier F, Ader F, Pilmis B, Catherinot E, Jarraud S, Lortholary O.

AP-HP, Hôpital Necker-Enfants malades, Centre d'Infectiologie Necker-Pasteur, IHU Imagine, Université Paris Descartes, Paris, France. e

Infect Dis Clin North Am 2017 Mar;31(1):123-135.

Abstract: Legionnaire's disease (LD) is mainly reported in apparently immunocompetent patients. Among them, risk factors include chronic lung disease and smoking. However, LD is also well reported among immunocompromised patients, particularly those treated with anti-tumor necrosis factor alpha therapy, patients with hematological malignancy, and transplant patients. This article discusses the available data on immunity against Legionella spp, epidemiology, clinical presentation, diagnosis, and treatment of LD in immunocompromised patients.


Severe Pneumonia Caused by Legionella pneumophila: Differential Diagnosis and Therapeutic Considerations

Chahin A, Opal SM.

Critical Care Division, Miriam Hospital, Brown University Alpert School of Medicine, Providence, RI, USA.

Infect Dis Clin North Am 2017 Mar;31(1):111-121.

Abstract: Severe legionella pneumonia poses a diagnostic challenge and requires early intervention. Legionnaire's disease can have several presenting signs, symptoms, and laboratory abnormalities that suggest that Legionella pneumophila is the pathogen, but none of these are sufficient to distinguish L. pneumophila pneumonia from other respiratory pathogens. L. pneumophila is primarily an intracellular pathogen and needs treatment with antibiotics that efficiently enter the intracellular space.


Legionnaire's Disease and Immunosuppressive Drugs

Htwe TH, Khardori NM.

Sentara Infectious Diseases Specialists, Sentara Medical Group, Norfolk, VA, USA.

Infect Dis Clin North Am 2017 Mar;31(1):29-42.

Abstract: Immunosuppressive agents predispose patients to legionnaire's disease. Patients receiving tumor necrosis factor antagonists are generally not severely immunocompromised by the underlying disease. In patients with malignancy receiving immunosuppressive therapies, it is difficult to balance the underlying disease versus the therapy used. Transplant recipients are often on multiple drugs, including immunosuppressants. It seems that immunosuppressive drugs add to the risk for legionella infection. The index of suspicion should be high for legionella infection early during a compatible clinical syndrome. The control of Legionella species and prevention of transmission should be the foremost goal in protecting susceptible populations from Legionnaire's disease.


Nervous System Abnormalities and Legionnaire's Disease

Halperin JJ.

Sidney Kimmel Medical College of Thomas Jefferson University, Summit, NJ, USA.

Infect Dis Clin North Am 2017 Mar;31(1):55-68.

Abstract: Although patients with Legionnaire's disease frequently develop alterations of consciousness, this is no more frequent than in patients hospitalized with other, equally severe forms of bacterial pneumonia. Legionella meningitis occurs rarely, if ever. Patients with Legionnaire's are susceptible to critical illness polyneuropathy/myopathy, as are other critically ill patients. Legionnaire's patients may develop MRI hyperdensities in the splenium of the corpus callosum, as may other patients with severe infections. Patients with Legionnaire's may be at increased risk of, and rarely develop, immune-mediated multifocal brain (acute disseminated encephalomyelitis) or peripheral nerve disease (Guillain-Barré syndrome).


Assessment of Antibiotic Susceptibility of Legionella pneumophila Isolated from Water Systems in Poland

Sikora A, Gładysz I, Kozioł-Montewka M, Wójtowicz-Bobin M, Stańczak T, Matuszewska R, Krogulska B.

Department of Medical Microbiology, Medical University of Lublin, Poland.

Ann Agric Environ Med 2017 Mar;24(1):66-69.

Abstract: Introduction and objective: Several studies have reported therapy failures in patients with Legionnaires’ disease; however, antimicrobial resistance of clinical and environmental isolates of Legionella spp. has not yet been documented. Routine susceptibility testing of Legionella spp. is not recommended because of difficulties in determining standard minimal inhibitory concentration values. The purpose of this study was to analyze the antimicrobial susceptibility of Legionella pneumophila strains isolated from a water supply system. Materials and method: Twenty-eight isolates of L. pneumophila (16-L. pneumophila SG 1, 12-L. pneumophila SG 2-14) obtained from water systems in public buildings in Poland were tested. Susceptibility testing was performed using the E-test method. The tested antibiotic were azithromycin, ciprofloxacin, and rifampicin. The medium used for the susceptibility testing was BCYE-, a special medium for Legionella cultivation. Results: Among the tested strains, L. pneumophila was the only one resistant to azithromycin. It was a strain of L. pneumophila SG 2-14 isolated from the water system in a sanitorium. All isolates were found to be sensitive to ciprofloxacin and rifampicin. However, the azithromycin-resistant strain exhibited higher ciprofloxacin and rifampicin MIC (1.5 μg/ml, and 0.19 μg/ml, respectively). The MIC50 for azithromycin, ciprofloxacin, and rifampicin were 0.032, 0.125, and 0.003 μg/ml, respectively. The MIC90 for azithromycin, ciprofloxacin, and rifampicin were 0.032, 0.125, and 0.003 μg/ml, respectively. Conclusions: Azithromycin resistance was found in one strain of L. pneumophila SG 2-14, but the resistance mechanism is unknown and needs further study. It is possible that therapeutic failures in Legionnaires' disease may be associated with bacterial resistance which should be taken into account. The antibiotic sensitivity testing described in this study could be helpful in detecting the resistance of clinical L. pneumophila isolates. Ciprofloxacin and rifampicin have good in vitro activity against environmental L. pneumophila SG 1 and SG 2-14 in Poland.


Legionella jamestowniensis Fatal Pneumonia in an Immunosuppressed Man

Edelstein PH.

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

J Infect Chemother 2017 Jan;23(1):59-61.

Abstract: A fatal case of Legionnaires' disease caused by Legionella jamestowniensis is reported in a severely immunocompromised patient with metastatic hepatocellular carcinoma, and liver and kidney transplants. L. jamestowniensis was cultured from two separate respiratory tract specimens and a PCR test for Legionella species was also positive from the same specimens. This is apparently the first reported case of human infection caused by L. jamestowniensis.


Influence of Antibiotics on the Detection of Bacteria by Culture-Based and Culture-Independent Diagnostic Tests in Patients Hospitalized with Community-Acquired Pneumonia

Harris AM, Bramley AM, Jain S, Arnold SR, Ampofo K, Self WH, Williams DJ, Anderson EJ, Grijalva CG, McCullers JA, Pavia AT, Wunderink RG, Edwards KM, Winchell JM, Hicks LA.

Centers for Disease Control and Prevention, Atlanta, Georgia.

Open Forum Infect Dis 2017 Feb;4(1):ofx014.

Abstract: Background: Specimens collected after antibiotic exposure may reduce culture-based bacterial detections. The impact on culture-independent diagnostic tests is unclear. We assessed the effect of antibiotic exposure on both of these test results among patients hospitalized with community-acquired pneumonia (CAP). Methods: Culture-based bacterial testing included blood cultures and high-quality sputum or endotracheal tube (ET) aspirates; culture-independent testing included urinary antigen testing (adults) for Streptococcus pneumoniae and Legionella pneumophila and polymerase chain reaction (PCR) on nasopharyngeal and oropharyngeal (NP/OP) swabs for Mycoplasma pneumoniae and Chlamydia pneumoniae. The proportion of bacterial detections was compared between specimens collected before and after either any antibiotic exposure (prehospital and/or inpatient) or only prehospital antibiotics and increasing time after initiation of inpatient antibiotics. Results: Of 4678 CAP patients, 4383 (94%) received antibiotics: 3712 (85%) only inpatient, 642 (15%) both inpatient and prehospital, and 29 (<1%) only prehospital. There were more bacterial detections in specimens collected before antibiotics for blood cultures (5.2% vs 2.6%; P<.01) and sputum/ET cultures (50.0% vs 26.8%; P<.01) but not urine antigen (7.0% vs 5.7%; P=.53) or NP/OP PCR (6.7% vs 5.4%; P=.31). For all diagnostic testing, bacterial detections declined with increasing time between inpatient antibiotic administration and specimen collection. Conclusions: Bacteria were less frequently detected in culture-based tests collected after antibiotics and in culture-independent tests that had longer intervals between antibiotic exposure and specimen collection. Bacterial yield could improve if specimens were collected promptly, preferably before antibiotics, providing data for improved antibiotic selection.


Comparison of Sputum Microbiome of Legionellosis-Associated Patients and Other Pneumonia Patients: Indications for Polybacterial Infections

Mizrahi H, Peretz A, Lesnik R, Aizenberg-Gershtein Y, Rodríguez-Martínez S, Sharaby Y, Pastukh N, Brettar I, Höfle MG, Halpern M.

Department of Evolutionary and Environmental Biology, Faculty of Natural Sciences, University of Haifa, Mount Carmel, Haifa, Israel.

Sci Rep 2017 Jan;7:40114.

Abstract: Bacteria of the genus Legionella cause water-based infections resulting in severe pneumonia. Here we analyze and compare the bacterial microbiome of sputum samples from pneumonia patients in relation to the presence and abundance of the genus Legionella. The prevalence of Legionella species was determined by culture, PCR, and Next Generation Sequencing (NGS). Nine sputum samples out of the 133 analyzed were PCR-positive using Legionella genus-specific primers. Only one sample was positive by culture. Illumina MiSeq 16S rRNA gene sequencing analyses of Legionella-positive and Legionella-negative sputum samples, confirmed that indeed, Legionella was present in the PCR-positive sputum samples. This approach allowed the identification of the sputum microbiome at the genus level, and for Legionella genus at the species and sub-species level. 42% of the sputum samples were dominated by Streptococcus. Legionella was never the dominating genus and was always accompanied by other respiratory pathogens. Interestingly, sputum samples that were Legionella positive were inhabited by aquatic bacteria that have been observed in an association with amoeba, indicating that amoeba might have transferred Legionella from the drinking water together with its microbiome. This is the first study that demonstrates the sputum major bacterial commensals and pathogens profiles with regard to Legionella presence.