All-trans-retinoic acid restores CD4+ T cell response after sepsis by inhibiting the expansion and activation of myeloid-derived suppressor cells.

BACKGROUND: Patients are susceptible to immunosuppression in late-stage of sepsis, in which myeloid-derived suppressor cells (MDSCs) is an important contributor. This study aims to investigate whether all-trans-retinoic acid (ATRA), which has been proved to inhibit MDSCs generation in cancer, will ameliorate sepsis-induced immuno-suppression through modulating MDSCs. METHODS: A clinically relevant "two-hit'' model of sepsis, the cecal ligation and puncture (CLP) model and secondary pneumonia model, were established in mice. The effects of ATRA on the mortality, the bacterial burden, the expansion and activity of CLP-induced MDSCs, as well as the function of CD4+ T cells were evaluated. RESULTS: In CLP model, ATRA was found to reduce frequency of MDSCs in spleen of mice and inhibit activity of MDSCs by regulating the generation and activity of arginase-1 and iNOS, and the secretion of immune-supressive cytokines. ATRA administration eventually reduced mortality of secondary infection by Legionella pneumophila in CLP-surviving mice, which might be associated with the restoration of CD4+ T cells proliferating and secreting activity. CONCLUSION: ATRA can restore CD4+ T cells dysfunction in sepsis by modulating the expansion and function of MDSCs and therefore provides a potential therapy that targets the immunosuppressive state of sepsis.

Community-acquired versus nosocomial Legionella pneumonia: factors associated with Legionella-related mortality.

Over the past decade, changes in the diagnosis and management of Legionella pneumonia occurred and risk factors for severe infection and increased mortality were identified. Previous reports found that nosocomial infection is associated with higher mortality while others showed no differences. We aimed to evaluate the differences in the clinical course and mortality rates between hospital-acquired pneumonia (HAP) and community-acquired pneumonia (CAP) caused by Legionella pneumophila. A retrospective cohort study of patients admitted due to Legionella pneumonia between January 2012 through November 2019 was conducted in a tertiary referral center (Rambam Health Care Campus, Haifa, Israel). The primary outcome was 30-day Legionella pneumonia-related mortality. A multivariable logistic regression was performed to determine whether a nosocomial infection is an independent predictor of mortality. One hundred nine patients were included. Seventy (64.2%) had CAP and 39 (35.8%) had HAP. The groups were comparable regarding age, gender, and comorbidities. Time to diagnosis was longer and the number of patients receiving initial empiric anti-Legionella spp. treatment was smaller in the HAP group (8 days [IQR 5.5-12.5] vs. 5 days [IQR 3-8], p < 0.001 and 65.5% vs. 78.6%, p = 0.003, respectively). Patients with HAP had higher 30-day mortality, 41% vs. 18.6%, p = 0.02. In a multivariable logistic regression model, only pneumonia severity index and nosocomial source were independently associated with increased mortality. HAP caused by Legionella spp. is independently associated with increased mortality when compared to CAP caused by the same pathogen. The possible reasons for this increased mortality include late diagnosis and delayed initiation of appropriate treatment.

Health after Legionnaires' disease: A description of hospitalizations up to 5 years after Legionella pneumonia.

BACKGROUND AND OBJECTIVES: Research on Legionnaires' Disease (LD) suggests there may be long-term health complications, but data are limited. This study investigated whether Intensive Care Unit (ICU) admission during LD hospitalization may be associated with adverse health outcomes and characterized subsequent discharge diagnoses in patients with LD up to 5 years post-LD. METHODS: We conducted a retrospective case series study with follow up for 5 years among patients hospitalized at a Department of Veterans Affairs (VA) Medical Center between 2005 and 2010 with LD. Data were collected from medical records on health history, LD severity (including ICU admission), and discharge diagnoses for 5 years post-LD or until death. We used ordinal logistic regression to explore associations between ICU admission and hospitalizations post-LD. Frequency counts were used to determine the most prevalent discharge diagnoses in the 5 years post-LD. RESULTS: For the 292 patients with laboratory-confirmed LD, those admitted to the ICU during LD hospitalization were more likely to have a greater number of hospitalizations within 5 years compared to non-ICU patients (ORHosp 1.92 CI95% 1.25, 2.95). Fifty-five percent (161/292) had ≥ 1 hospitalization within 5 years post-LD. After accounting for pre-existing diagnosis codes in patients with at least one hospitalization in the 2 years prior to LD (n = 77/161 patients, 47.8%), three of the four most frequent new diagnoses in the 5 years post-LD were non-chronic conditions: acute renal failure (n = 22, 28.6%), acute respiratory failure (n = 17, 22.1%) and unspecified pneumonia (n = 15, 19.5%). CONCLUSIONS: Our findings indicate that LD requiring ICU admission is associated with more subsequent hospitalizations, a factor that could contribute to poorer future health for people with severe LD. In addition to chronic conditions prevalent in this study population, we found new diagnoses in the 5-year post-LD period including acute renal failure. With LD incidence increasing, more research is needed to understand conditions and factors that influence long term health after LD.

[Severe community-acquired pneumonia caused by Legionella pneumophila with acute respiratory failure: clinical characteristics and prognosis of 34 cases].

Objective: To describe the clinical characteristics and treatment of severe community-acquired pneumonia(SCAP) caused by Legionella pneumophila with acute respiratory failure and to analyze the risk factors for mortality. Methods: From October 2011 to October 2019, 34 patients were diagnosed with SCAP caused by Legionella pneumophila with acute respiratory failure.There were 25 males and 9 females, aged from 17 to 82 years, with a median age of 61 (48, 69) years. According to the prognosis, the patients were divided into a survival group and a death group for comparative analysis.The survival group included 24 patients, 17 males and 7 females, with a median age of 65 (55, 70) years. There were 10 cases in the death group, 8 males and 2 females, with a median age of 53 (50, 58) years. Multivariable logistic regression analysis was used for risk factors of ICU mortality. Results: The median time of admission to ICU was 7 (5, 11) days, the median time of stay in RICU was 12 (7, 22) days, and the PaO(2)/FiO(2) was 134 (91, 216) mmHg(1 mmHg=0.133 kPa). Ten patients died during ICU hospitalization, with a mortality of 29%. Sequential organ failure assessment (SOFA) of death group was 9 (7, 12), which was significantly higher than that of the survival group [4 (3, 8)], P=0.018. The time from onset of pneumonia symptoms to initiation of targeted treatment of the death group was 10 (7, 14) d, which was significantly longer than that of the survival group of [4 (3, 7) d], P=0.019. Multivariable logistic regression analysis showed that SOFA score (OR=1.461, 95%CI 1.041-2.051, P=0.028) and the time from onset of pneumonia symptoms to initiation of targeted treatment (OR=1.293, 95%CI 1.029-1.625, P=0.027) were independent risk factors for hospital mortality. Conclusions: The ICU mortality of severe legionella pneumonia was high. Critical organ dysfunctions and delayed initial targeted treatment were related with the increase of ICU mortality.

Probable reinfection with Legionella pneumophila - A case report.

In Germany community-acquired Legionnaires' disease is usually caused by the species Legionella pneumophila. Recurrent cases of Legionnaires' disease are rarely reported and are due either to a second infection (reinfection) or a relapse of a previous case. We report a case of recurrent Legionnaires' disease in an 86-year-old female patient infected with Legionella pneumophila serogroup 1, monoclonal antibody-subtype Knoxville, sequence type unknown. Between the two disease incidents the patient had completely recovered. Legionella pneumophila was detected with the monoclonal antibody-subtype Knoxville, sequence type 182, in the drinking water of the patient's apartment. Exposure to contaminated drinking water was interrupted after the first incident exposure through the application of point-of-use water filters. The filters were later removed due to low water pressure, and the second illness occurred thereafter. It is unclear if immunological predisposition has contributed to this case of probable reinfection of Legionnaires' disease. Clinical, microbiological and epidemiological information combined suggest this is a case of reinfection of Legionnaires' disease. In cases of recurrent Legionnaires' disease complete collection of patient and water samples is necessary to differentiate relapse from reinfection cases, to implicate the source of infection and to gain more evidence for the role of immunological predisposition.

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

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.

Legionnaires' disease at a medical center in southern Taiwan.

BACKGROUND/PURPOSE: Legionella pneumophila had been recognized as a pathogen for both healthcare-associated and community-acquired pneumonia. We aimed to evaluate clinical features and outcomes of patients with Legionnaires' disease at a tertiary medical center in southern Taiwan. METHODS: From January 2005 to December 2013, a retrospective study of adult cases of Legionnaires' disease was conducted in a 1200-bed tertiary hospital. Their medical records were reviewed for further evaluation and analysis. RESULTS: A total of 61 cases of Legionnaires' disease were identified during the study period. Their mean age was 61.1 years, with male predominance (43, 70.5%). Among them, 30 (49.2%) had healthcare-associated pneumonia (HCAP), 20 (32.8%) had community-acquired pneumonia, and notably 11 (18.0%) were caregivers. Patients with healthcare-associated pneumonia tend to have higher Charlson comorbidity scores than those with community-acquired pneumonia (3.6±2.4 vs. 1.9±1.9, p=0.008) and caregivers (0.5±0.5, p<0.001). Six patients died, resulting in an in-hospital mortality rate of 9.8%. Underlying cancer (66.7% vs. 20.0%, p=0.028) and a higher Charlson comorbidity score (4.7±2.6 vs. 2.2±2.2, p=0.013) were related to a fatal outcome. CONCLUSION: L. pneumophila remains an important pathogen for pneumonia acquired from the community or associated with healthcare facility. Healthy caregivers may potentially be at risk for Legionella infection in certain clinical settings.

Antimicrobial strategy for severe community-acquired legionnaires' disease: a multicentre retrospective observational study.

Background: Legionnaires' disease (LD) is an important cause of community-acquired pneumonia with high mortality rates in the most severe cases. Objectives: To evaluate the effect of antimicrobial strategy on ICU mortality. Methods: Retrospective, observational study including patients admitted to 10 ICUs for severe community-acquired LD over a 10 year period (2005-15) and receiving an active therapy within 48 h of admission . Patients were stratified according to the antibiotic strategy administered: (i) fluoroquinolone-based versus non-fluoroquinolone-based therapy; and (ii) monotherapy versus combination therapy. The primary endpoint was in-ICU mortality. A multivariable Cox model and propensity score analyses were used. Results: Two hundred and eleven patients with severe LD were included. A fluoroquinolone-based and a combination therapy were administered to 159 (75%) and 123 (58%) patients, respectively. One hundred and forty-six patients (69%) developed acute respiratory distress syndrome and 54 (26%) died in the ICU. In-ICU mortality was lower in the fluoroquinolone-based than in the non-fluoroquinolone-based group (21% versus 39%, P = 0.01), and in the combination therapy than in the monotherapy group (20% versus 34%, P = 0.02). In multivariable analysis, a fluoroquinolone-based therapy, but not a combination therapy, was associated with a reduced risk of mortality [HR = 0.41, 95% CI 0.19-0.89; P = 0.02]. Conclusions: Patients with severe LD receiving a fluoroquinolone-based antimicrobial regimen in the early course of management had a lower in-ICU mortality, which persisted after adjusting for significant covariates.

Microbiology and Epidemiology of Legionnaire's Disease.

Legionnaire's disease (LD) is the pneumonic form of legionellosis caused by aerobic gram-negative bacilli of the genus Legionella. Individuals become infected when they inhale aerosolized water droplets contaminated with Legionella species. Forty years after the identification of Legionella pneumophila as the cause of the 1976 pneumonia outbreak in a hotel in Philadelphia, we have non-culture-based diagnostic tests, effective antibiotics, and preventive measures to handle LD. With a mortality rate still around 10%, underreporting, and sporadic outbreaks, there is still much work to be done. In this article, the authors review the microbiology, laboratory diagnosis, and epidemiology of LD.

[Prognostic factors in adult patients hospitalized for pneumonia caused by Legionella pneumophila]. / Factores pronósticos en adultos hospitalizados por neumonía causada por Legionella pneumophila.

INTRODUCTION: Legionellosis is a multisystem bacterial disease, which causes pneumonia with high mortality in patients with comorbidity and admitted in intensive care units (ICU). OBJECTIVE: Determine predictors of mortality or ICU admission. METHODS: Retrospective follow-up of patients diagnosed with Legionella pneumophila pneumonia in Complexo Hospitalario Universitario de A Coruña. Period 2000-2013 (n=240). Analysis of multivariate logistic regression was performed. RESULTS: Mean age was 57.2±15.4 years old, 88.3% were male. Average score of comorbidity (Charlson score) was 2.3±2.3. There was a clear seasonal variation. Predominant symptoms were fever (92.5%), dry cough (38.1%) and dyspnea (33.9%). Creatinine clearance was lower than 60 mL/min/1.73 m² in 29.7% and sodium<135 mEq/l in 58.3%. Admission to ICU rate was 16.3% and 10.8% needs mechanical ventilation. Inhospital mortality rate was 4.6%, rising to 23.1% in patients admitted to ICU. Variables associated to predict ICU admission were age (OR=0.96), liver disease (OR=7.13), dyspnea (OR=4.33), delirium (OR=5.86) and high levels of lactatedehydrogenase (OR=1.002). Variables associated with inhospital mortality were Charlson index (OR=1.70), mechanical ventilation (OR=31.44) and high levels of lactatedehydrogenase (OR=1.002). DISCUSSION: Younger patients with liver disease, dyspnea and confusion are more likely to be admitted to ICU. Comorbidity, mechanical ventilation and elevated LDH levels are associated with higher mortality rate.

Factores pronósticos en adultos hospitalizados por neumonía causada por Legionella pneumophila / Prognostic factors in adult patients hospitalized for pneumonia caused by Legionella pneumophila

Introduction: Legionellosis is a multisystem bacterial disease, which causes pneumonia with high mortality in patients with comorbidity and admitted in intensive care units (ICU). Objective: Determine predictors of mortality or ICU admission. Methods: Retrospective follow-up of patients diagnosed with Legionella pneumophila pneumonia in Complexo Hospitalario Universitario de A Coruña. Period 2000-2013 (n = 240). Analysis of multivariate logistic regression was performed. Results: Mean age was 57.2 ± 15.4 years old, 88.3% were male. Average score of comorbidity (Charlson score) was 2.3 ± 2.3. There was a clear seasonal variation. Predominant symptoms were fever (92.5%), dry cough (38.1%) and dyspnea (33.9%). Creatinine clearance was lower than 60 mL/min/1.73 m² in 29.7% and sodium < 135 mEq/l in 58.3%. Admission to ICU rate was 16.3% and 10.8% needs mechanical ventilation. Inhospital mortality rate was 4.6%, rising to 23.1% in patients admitted to ICU. Variables associated to predict ICU admission were age (OR = 0.96), liver disease (OR = 7.13), dyspnea (OR = 4.33), delirium (OR = 5.86) and high levels of lactatedehydrogenase (OR = 1.002). Variables associated with inhospital mortality were Charlson index (OR = 1.70), mechanical ventilation (OR = 31.44) and high levels of lactatedehydrogenase (OR = 1.002). Discussion: Younger patients with liver disease, dyspnea and confusion are more likely to be admitted to ICU. Comorbidity, mechanical ventilation and elevated LDH levels are associated with higher mortality rate.

Introducción: La legionelosis es una enfermedad bacteriana multisistémica, causante de neumonías con mortalidad elevada en pacientes con comorbilidad e ingresos en Unidad de Cuidados Intensivos (UCI). Objetivo: Determinar factores pronósticos de mortalidad o ingreso en UCI. Material y Métodos: Estudio de seguimiento retrospectivo de pacientes diagnosticados de neumonía por Legionella pneumophila en Complexo Hospitalario Universitario de A Coruña (España). Período 2000-2013 (n = 240), con análisis de regresión logística multivariada. Resultados: La edad media fue 57,2 ± 15,4 años, 88,3% fueron hombres. La puntuación media de comorbilidad (score Charlson) fue 2,3 ± 2,3. Existe clara estacionalidad. La clínica predominante fue fiebre (92,5%), tos seca (38,1%) y disnea (33,9%). El 29,7% presentó aclaramiento de creatinina < 60 mL/min/1,73 m² y el 58,3% sodio < 135 mEq/l. Un 16,3% ingresó en UCI, precisando ventilación mecánica invasiva el 10,8%. La mortalidad global fue 4,6% y de 23,1% en ingresados en UCI. Variables asociadas para predecir ingreso en UCI fueron menor edad (OR = 0,96), hepatopatía (OR = 7,13), disnea (OR = 4,33), síndrome confusional (OR = 5,86) y lactato deshidrogenasa elevada (OR = 1,002). Las variables asociadas a mortalidad intrahospitalaria fueron índice de Charlson (OR = 1,70), ventilación mecánica invasiva (OR = 31,44) y cifras elevadas de lactato deshidrogenasa (OR = 1,002). Discusión: Pacientes jóvenes, con hepatopatía, disnea o confusión tienen más probabilidad de ingresar en UCI. Comorbilidad, ventilación mecánica y lactato deshidrogenasa elevada se asocian a mortalidad.

Legionnaires' disease and associated comorbid conditions as causes of death in the U.S., 2000-2010.

OBJECTIVE: Recent U.S. outbreaks of Legionnaires' disease (LD) underscore the virulent nature of this infectious pneumonia. To date, only a paucity of literature has described the mortality burden of LD. This study updates LD mortality using U.S. multiple-cause-of-death data from 2000-2010. METHODS: We calculated crude and age-adjusted rates for LD mortality for age, sex, race, state, Census region, and year. We conducted Poisson regression to assess seasonal and temporal trends. We generated matched odds ratios (MORs) to describe the association between LD-related deaths and other comorbid conditions listed on the death certificates. RESULTS: We identified a total of 1,171 LD-related deaths during 2000-2010. The age-adjusted mortality rate remained relatively static from 2000 (0.038 per 100,000 population, 95% confidence interval [CI] 0.031, 0.046) to 2010 (0.040 per 100,000 population, 95% CI 0.033, 0.047). The absolute number increased from 107 to 135 deaths during this period, with adults ≥45 years of age having the highest caseload. Overall, LD mortality rates were 2.2 times higher in men than in women. White people accounted for nearly 83.3% of all LD-related deaths, but the age-adjusted mortality rates for black and white people were similar. Comorbid conditions such as leukemia (MOR=4.8, 95% CI 3.5, 6.6) and rheumatoid arthritis (MOR=5.6, 95% CI 3.3, 9.4) were associated with LD diagnosis on death certificates. CONCLUSION: Comorbid conditions that could lead to an immunocompromised state were associated with fatal LD on U.S. death certificates. Characterization of LD mortality burden and related comorbidities has practice implications for clinical medicine and public health surveillance.

Legionnaires' Disease Outbreak at a Long-Term Care Facility Caused by a Cooling Tower Using an Automated Disinfection System--Ohio, 2013.

On July 9, 2013, an outbreak of Legionnaires' disease (LD) was identified at Long-Term Care Facility A in central Ohio. This article describes the investigation of the outbreak and identification of the outbreak source, a cooling tower using an automated biocide delivery system. In total, 39 outbreak LD cases were identified; among these, six patients died. Water samples from a cooling tower were positive for Legionella pneumophila serogroup 1, reactive to monoclonal antibody 2, with matching sequence type to a patient isolate. An electronic control system turned off cooling tower pumps during low-demand periods, preventing delivery of disinfectant by a timed-release system, and leading to amplification of Legionella in the cooling tower. Guidelines for tower maintenance should address optimal disinfection when using automated systems.

Legionnaires' disease in Italy: results of the epidemiological surveillance from 2000 to 2011.

According to the Italian Surveillance System for Legionnaires' disease (LD), physicians must fill in a form for every case and send it through the Local Health Units to the National Institute of Health (Istituto Superiore di Sanità, ISS). Forms reported in the period from 2000 to 2011 were analysed and discussed. A total of 9,803 cases of LD were reported to ISS during the study period. The median age of cases was 63 years, with a ratio male/female of 2.6 and a case fatality rate of 11.8%. The number of cases has been steadily increasing from 192 cases in 2000 to 1,235 in 2010 and 1,008 cases in 2011. The reported cases showed a geographical gradient, with the highest number notified in the north and the lowest in the south. The majority of cases (73.0%) were community-acquired, followed by travel-associated (13.5%) and healthcare-associated cases (9.3%), cases acquired in long-term care facilities (2.1%), and other types of exposure (2.1%). Even though the increasing trend of LD in Italy indicates an improvement in the ability to detect and report cases, the geographical gradient highlights the existence of low reporting areas where the epidemiological surveillance of LD should be further strengthened.

Etiology and factors contributing to the severity and mortality of community-acquired pneumonia.

OBJECTIVE: Community-acquired pneumonia (CAP) remains a major cause of death. No studies have reported the use of rapid influenza diagnostic tests (RIDT) for the etiological diagnosis, and the factors contributing to severity and mortality have not yet been fully investigated. The aim of this study was to review the etiologies of CAP using RIDT and to identify risk factors related to the severity and mortality of the disease. METHODS: This retrospective study assessed these factors in hospitalized patients, with special emphasis on microbial etiology. RESULTS: A total of 1,032 patients aged 63.9±18.3 years were studied, 66.2% of whom were men. Microbial identification was obtained in 57.0% of the cases. The most frequent causative microbial agents were Streptococcus pneumoniae, Mycoplasma pneumoniae and the influenza virus, and the second most frequent pathogens in the patients with severe CAP and the non-survivors were S. pneumoniae and the influenza virus. Age (≥65 years), chronic obstructive pulmonary disease, congestive heart failure, diabetes mellitus, dementia and Legionella spp. infection and polymicrobial infection were each found to be independent factors related to severity in the multivariate analysis, whereas "unidentified pathogen" was found to be an independent factor for non-severe CAP. Age (≥65 years), chronic pulmonary aspergillosis, post-lung cancer surgery and severe CAP were found to be independent factors for non-survival according to a multivariate analysis. CONCLUSION: In addition to S. pneumoniae, the influenza virus was a frequent cause of CAP overall and a frequent causative pathogen in both severe cases of CAP and non-survivors. Legionella spp. infection and polymicrobial infection were found to be an independent factor for the severity of CAP along with advanced age and certain comorbidities. An advanced age, certain respiratory comorbidities and severe CAP were found to be important independent factors for the mortality of CAP.

Community-acquired Legionella Pneumonia in the intensive care unit: Impact on survival of combined antibiotic therapy.

OBJECTIVES: To compare intensive care unit (ICU) mortality in patients with severe community-acquired pneumonia (SCAP) caused by Legionella pneumophila receiving combined therapy or monotherapy. METHODS: A prospective multicenter study was made, including all patients with sporadic, community-acquired Legionnaires' disease (LD) admitted to the ICU. Admission data and information on the course of the disease were recorded. Antibiotic prescriptions were left to the discretion of the attending physician and were not standardized. RESULTS: Twenty-five cases of SCAP due to L. pneumophila were included, and 7 patients (28%) out of 25 died after a median of 7 days of mechanical ventilation. Fifteen patients (60%) presented shock. Levofloxacin and clarithromycin were the antibiotics most commonly used in monotherapy, while the most frequent combination was rifampicin plus clarithromycin. Patients subjected to combination therapy presented a lower mortality rate versus patients subjected to monotherapy (odds ratio for death [OR] 0.15; 95%CI 0.02-1.04; p=0.08). In patients with shock, this association was stronger and proved statistically significant (OR for death 0.06; 95%CI 0.004-0.86; p=0.04). CONCLUSIONS: Combined antibiotic therapy decreases mortality in patients with SCAP and shock caused by L. pneumophila.

Legionnaires' disease--risk management.

Steve Mount, an independent Legionella management consultant and trainer with over 25 years' previous experience in microbiology and UKAS-accredited Legionella analysis, underlines the rising number of nosocomial cases of Legionnaires' disease in recent years, and explains the key risk assessment, management, and monitoring steps that must be taken by those responsible for hospital water systems to comply with legislation governing the 'control and management' of Legionella risk.

Factors associated with hospital mortality in community-acquired legionellosis in France.

The aims of this study were to describe the clinical, biological and radiological features of community-acquired (CA) Legionnaires' disease (LD) and identify the predictors of mortality in hospitalised patients. Demographic data, risk factors, clinical and biological features, medical management, complications, and outcome from 540 hospitalised patients with confirmed CA LD were prospectively recorded. 8.1% of patients (44 out of 540) died. The predictors of survival after Kaplan-Meier analysis were male sex (p = 0.01), age <60 yrs (p = 0.02), general symptoms (p = 0.006), intensive care unit (ICU) stay (p<0.001), and class II-III Pneumonia Severity Index score (p = 0.004). Six predictors of death were identified by multivariate analysis: age (per 10-yr increment) (relative hazard (RH) 1.50, 95% CI 1.21-1.87), female sex (RH 2.00, 95% CI 1.08-3.69), ICU admission (RH 3.31, 95% CI 1.67-6.56), renal failure (RH 2.73, 95% CI 1.42-5.27), corticosteroid therapy (RH 2.54, 95% CI 1.04-6.20) and C-reactive protein (CRP) >500 mg · L(-1) (RH 2.14, 95% CI 1.02-4.48). Appropriate antibiotic therapy was prescribed for 70.8% (292 out of 412) of patients after admission and for 99.8% (537 out of 538) of patients after diagnosis confirmation. In conclusion, female sex, age, ICU stay, renal failure, corticosteroid treatment and increased level of CRP are significant risk factors for mortality in CA LD.

[Interdisciplinary management of a large Legionella outbreak in Germany]. / Interdisziplinäres Management eines länderübergreifenden Legionellenausbruchs.

Between December 2009 and the end of January 2010, the largest hitherto known outbreak of Legionella in Germany took place in the cities of Ulm and Neu-Ulm. Of a total of 64 patients involved, 60 patients had to be hospitalized, and 5 patients died from the infection. This event was caused by a wet cooling tower of a large air conditioning system in the city center of Ulm. The search for the source of the Legionella emission was extremely difficult, since these plants are neither notifiable nor subject to authorization in Germany. We report about the search for the source and the measures to control the outbreak. We also discuss communication and coordination during these investigations. Regulatory measures as proposed by the World Health Organization (WHO) and the European Network for Legionellosis (EWGLI) and already implemented in numerous other European countries would be desirable to prevent such outbreaks in the future.