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

Chidiac, Christian; Che, Didier; Pires-Cronenberger, S.; Jarraud, Sophie; Campese, C; Bissery, Anne; Weinbreck, P.; Brun‐Buisson, Christian; Sollet, J.-P.; Écochard, René; Desenclos, J C; Etienne, Jérôme; Vanhems, Philippe

doi:10.1183/09031936.00076911

Cited by 53 publications

(43 citation statements)

References 28 publications

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“…29–33 In our cohort, older age, diabetes mellitus, and chronic respiratory disease were each significantly associated with an increased risk of LD (Table 4) in a univariate analysis. Smoking was also associated with increased LD risk that did not reach significance in the univariate analysis (p=0.2).…”

Section: Resultsmentioning

confidence: 82%

A TLR6 polymorphism is associated with increased risk of Legionnaires’ disease

et al. 2013

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Legionella pneumophila (Lp), the etiologic agent of Legionnaires’ Disease (LD), is an important cause of community-acquired and nosocomial pneumonia. However, the host immune and genetic determinants of human susceptibility to Lp are poorly understood. Here we show that both TLR6 and TLR1 cooperate with TLR2 to recognize Lp in transfected HEK293 cells. We also perform a human genetic association study of 14 candidate single nucleotide polymorphisms in Toll-like receptors (TLRs) 1, 2, and 6 in 98 LD cases and 268 controls from the Netherlands. No polymorphisms in TLR1 or TLR2 were associated with LD. A TLR6 polymorphism, 359T>C (rs5743808), was associated with an elevated risk of LD in genotypic and dominant (OR 5.83, p=7.9×10−5) models. The increased risk in persons with 359 TC or CC genotypes was further enhanced among smokers. In a multivariate model, 359T>C was associated with a higher risk of LD (OR 4.24, p=0.04), than any other variable, including age and smoking. Together, these data suggest that the human TLR6 variant, 359T>C, is an independent risk factor for LD.

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Section: Resultsmentioning

confidence: 82%

A TLR6 polymorphism is associated with increased risk of Legionnaires’ disease

et al. 2013

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“…Legionellosis is an acute pneumonia caused by inhalation of aerosols containing Legionella sp., with L. pneumophila serogroup (sg) 1 accounting for more than 90% of human infections ( Newton et al, 2010; Carratalà and Garcia-Vidal, 2010 ). The macrolides (especially azithromycin) and the fluoroquinolones are first-line antibiotics for the treatment of legionellosis patients ( Chidiac et al, 2012; Jespersen et al, 2010; Yu et al, 2009; Pedro-Botet and Yu, 2009; Burdet et al, 2014 ). However, treatment failures and relapses may occur despite administration of an appropriate antibiotic therapy ( Chidiac et al, 2012; Jespersen et al, 2010; Yu et al, 2009; Pedro-Botet and Yu, 2009; Burdet et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Hidden Selection of Bacterial Resistance to Fluoroquinolones In Vivo: The Case of Legionella pneumophila and Humans

et al. 2015

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BackgroundInfectious diseases are the leading cause of human morbidity and mortality worldwide. One dramatic issue is the emergence of microbial resistance to antibiotics which is a major public health concern. Surprisingly however, such in vivo adaptive ability has not been reported yet for many intracellular human bacterial pathogens such as Legionella pneumophila.MethodsWe examined 82 unrelated patients with Legionnaire's disease from which 139 respiratory specimens were sampled during hospitalization and antibiotic therapy. We both developed a real time PCR assay and used deep-sequencing approaches to detect antibiotic resistance mutations in L. pneumophila and follow their selection and fate in these samples.FindingsWe identified the in vivo selection of fluoroquinolone resistance mutations in L. pneumophila in two infected patients treated with these antibiotics. By investigating the mutational dynamics in patients, we showed that antibiotic resistance occurred during hospitalization most likely after fluoroquinolone treatment.InterpretationIn vivo selection of antibiotic resistances in L. pneumophila may be associated with treatment failures and poor prognosis. This hidden resistance must be carefully considered in the therapeutic management of legionellosis patients and in the control of the gradual loss of effectiveness of antibiotics.

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“…Legionella pneumophila, especially serogroup 1 (sg1), is the major cause of LD, which remains a serious disease. Several host-related risk factors have been clearly identified [2–4] , including older age, male sex, smoking, diabetes, chronic heart or lung disease, cancer or hematologic malignancy and steroid use or any immunosuppressive therapy.…”

Section: Introductionmentioning

confidence: 99%

Epidemiologic characteristics associated with ST23 clones compared to ST1 and ST47 clones of Legionnaires disease cases in France

Cassier

Campese

Strat

et al. 2015

New Microbes and New Infections

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In France, approximately 1200 cases of Legionnaires disease (LD) are reported annually, and isolates are available for approximately 20% of cases identified since 2000. All Legionella pneumophila serogroup 1 (sg1) isolates are characterized by sequence-based typing at the National Reference Centre. LD cases caused by L. pneumophila sg1 reported from 2008 through 2012 were considered for the study. Our study objective was to describe cases according to their sequence type (ST). We also constructed multivariable modified Poisson regression models to estimate the incidence rate ratio (IRR) and to identify characteristics potentially associated with ST23 clones compared to ST1 and ST47 clones. We studied 1192 patients infected by ST1 (n = 109), ST23 (n = 236), ST47 (n = 123) or other STs (n = 724). The geographic distribution of the ST23 cases across the country was significantly different compared to other ST groups. This genotype was significantly associated with the absence of corticosteroid therapy compared to ST1 (IRR = 0.56; p 0.016). Concerning exposure, the ST23 genotype was significantly less associated with hospital-acquired infections compared to ST1 (IRR = 0.32; p 0.001), but it was more associated with infections acquired in hospitals and elderly settings compared with ST47. Finally, the ST23 genotype was less frequently associated with travel than other STs. Despite the large number of cases of ST23 infection, we did not identify any characteristics specific to this ST. However, we identified independent associations between ST1 and nosocomial transmission and steroid therapy. These findings should encourage further exploration, especially in terms of environmental diffusion, strain virulence and host factors.

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

Cited by 53 publications

References 28 publications

A TLR6 polymorphism is associated with increased risk of Legionnaires’ disease

A TLR6 polymorphism is associated with increased risk of Legionnaires’ disease

Hidden Selection of Bacterial Resistance to Fluoroquinolones In Vivo: The Case of Legionella pneumophila and Humans

Epidemiologic characteristics associated with ST23 clones compared to ST1 and ST47 clones of Legionnaires disease cases in France

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