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Valour F.,Service des Maladies Infectieuses et Tropicales | Valour F.,University Claude Bernard Lyon 1 | Karsenty J.,Service des Maladies Infectieuses et Tropicales | Bouaziz A.,Service des Maladies Infectieuses et Tropicales | And 12 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2014

Prolonged antimicrobial therapy is recommended for methicillin-susceptible Staphylococcus aureus (MSSA) bone and joint infections (BJI), but its safety profile and risk factors for severe adverse events (SAE) in clinical practice are unknown. We addressed these issues in a retrospective cohort study (2001 to 2011) analyzing antimicrobial-related SAE (defined according to the Common Terminology Criteria for Adverse Events) in 200 patients (male, 62%; median age, 60.8 years [interquartile range {IQR}, 45.5 to 74.2 years]) with MSSA BJI admitted to a reference regional center with acute (66%) or chronic arthritis (7.5%), osteomyelitis (9.5%), spondylodiscitis (16%), or orthopedic device-related infections (67%). These patients received antistaphylococcal therapy for a median of 26.6 weeks (IQR, 16.8 to 37.8 weeks). Thirty-eight SAE occurred in 30 patients (15%), with a median time delay of 34 days (IQR, 14.75 to 60.5 days), including 10 patients with hematologic reactions, 9 with cutaneomucosal reactions, 6 with acute renal injuries, 4 with hypokalemia, and 4 with cholestatic hepatitis. The most frequently implicated antimicrobials were antistaphylococcal penicillins (ASP) (13 SAE/145 patients), fluoroquinolones (12 SAE/187 patients), glycopeptides (9 SAE/101 patients), and rifampin (7 SAE/107 patients). Kaplan-Meier curves and stepwise binary logistic regression analyses were used to determine the risk factors for the occurrence of antimicrobial-related SAE. Age (odds ratio [OR], 1.479 for 10- year increase; 95% confidence interval [CI], 1.116 to 1.960; P 0.006) appeared to be the only independent risk factor for SAE. In patients receiving ASP or rifampin, daily dose (OR, 1.028; 95% CI, 1.006 to 1.051; P 0.014) and obesity (OR, 8.991; 95% CI, 1.453 to 55.627; P 0.018) were associated with the occurrence of SAE. The high rate of SAE and their determinants highlighted the importance of the management and follow-up of BJI, with particular attention to be paid to older persons, especially for ASP dosage, and to rifampin dose adjustment in obese patients. Copyright © 2014, American Society for Microbiology. All Rights Reserved. Source


Stegger M.,Statens Serum Institute | Andersen P.S.,Statens Serum Institute | Kearns A.,Public Health England | Pichon B.,Public Health England | And 6 more authors.
Clinical Microbiology and Infection | Year: 2012

The recent finding of a new mecA homologue, mecA LGA251, with only 70% nucleotide homology to the conventional mecA gene has brought the routine testing for mecA as a confirmatory test for methicillin-resistant Staphylococcus aureus (MRSA) into question. A multiplex PCR was designed to differentiate mecA LGA251 from the known mecA together with detection of lukF-PV and the spa gene fragments, enabling direct spa typing by sequencing of the PCR amplicons. The PCR analysis and subsequent spa typing were validated on a large collection (n=185) of contemporary MRSA and methicillin-sensitive S. aureus isolates, including 127 isolates carrying mecA LGA251. The mecA LGA251 gene was situated in staphylococcal cassette chromosome mec type XI elements, and sequence variation within a 631-bp fragment of mecA LGA251 in 79 isolates indicated a very conserved gene sequence. Following a successful validation, the multiplex PCR strategy was implemented in the routine testing of MRSA for national surveillance. Over a 2-month period, among 203 samples tested, 12 new MRSA cases caused by isolates carrying mecA LGA251 were identified, emphasizing the clinical importance of testing for these new MRSA isolates. © 2011 Statens Serum Institut. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases. Source


Rasigade J.-P.,Center National Of Reference Des Staphylocoques
Journal of Infectious Diseases | Year: 2010

Background. Panton-Valentine leukocidin (PVL)-positive methicillin- susceptible Staphylococcus aureus and methicillin-resistant S. aureus (MSSA and MRSA, respectively) are both associated with severe infections, such as necrotizing pneumonia. The epidemiological profile of PVL-positive community-acquired (CA) MRSA has been extensively studied, but few corresponding data on PVL-positive MSSA are available. Objectives. The objectives of the study were to investigate the global population structure of PVL-positive MSSA, to compare it with that reported for CA-MRSA, and thus to examine the phylogenetic relationship between these pathogens. Methods. We determined the agr types, multilocus sequence types, and toxin gene profiles of 211 PVL-positive MSSA clinical isolates collected in 19 countries throughout the world between 1981 and 2007. Results. The predominant lineages of PVL-positive MSSA were agr3/ST30, agr4/ST121, agr3/ST1, agr2/ST5, and agr3/ST80. Except for agr4/ST121, these lineages are also reported to be prevalent among CA-MRSA. PVL-positive MSSA lineages that are genetically related to CA-MRSA have gradually replaced other lineages (especially agr4/ST121) over the past 2 decades. Within a given sequence type, the toxin gene content of PVL-positive MSSA strains was very similar to that of PVL-positive CA-MRSA. Conclusions. The molecular epidemiological profiles of PVL-positive MSSA and CA-MRSA are dynamically interrelated, with the former appearing to constitute a reservoir for the latter. © 2010 by the Infectious Diseases Society of America. All rights reserved. Source


Duval X.,University Paris Diderot | Duval X.,French Institute of Health and Medical Research | Delahaye F.,Hospices Civils de Lyon | Delahaye F.,University of Lyon | And 19 more authors.
Journal of the American College of Cardiology | Year: 2012

Objectives: The goal of this study was to evaluate temporal trends in infective endocarditis (IE) incidence and clinical characteristics after 2002 French IE prophylaxis guideline modifications. Background: There are limited data on changes in the epidemiology of IE since recent guidelines recommended restricting the indications of antibiotic prophylaxis of IE. Methods: Three 1-year population-based surveys were conducted in 1991, 1999, and 2008 in 3 French regions totaling 11 million inhabitants age <20 years. We prospectively collected IE cases from all medical centers and analyzed age- and sex-standardized IE annual incidence trends. Results: Overall, 993 expert-validated IE cases were analyzed (323 in 1991; 331 in 1999; and 339 in 2008). IE incidence remained stable over time (95% confidence intervals given in parentheses/brackets): 35 (31 to 39), 33 (30 to 37), and 32 (28 to 35) cases per million in 1991, 1999, and 2008, respectively. Oral streptococci IE incidence did not increase either in the whole patient population (8.1 [6.4 to 10.1], 6.3 [4.8 to 8.1], and 6.3 [4.9 to 8.0] in 1991, 1999, and 2008, respectively) or in patients with pre-existing native valve disease. The increased incidence of Staphylococcus aureus IE (5.2 [3.9 to 6.8], 6.8 [5.3 to 8.6], and 8.2 [6.6 to 10.2]) was not significant in the whole patient population (p = 0.228) but was significant in the subgroup of patients without previously known native valve disease (1.6 [0.9 to 2.7], 3.7 [2.6 to 5.1], and 4.1 [3.0 to 5.6]; p = 0.012). Conclusions: Scaling down antibiotic prophylaxis indications was not associated with an increased incidence of oral streptococcal IE. A focus on avoidance of S. aureus bacteremia in all patients, including those with no previously known valve disease, will be required to improve IE prevention. © 2012 American College of Cardiology Foundation. Source


Khanafer N.,CNRS Biometry and Evolutionary Biology Laboratory | Sicot N.,Center National Of Reference Des Staphylocoques | Vanhems P.,CNRS Biometry and Evolutionary Biology Laboratory | Dumitrescu O.,Center National Of Reference Des Staphylocoques | And 8 more authors.
BMC Infectious Diseases | Year: 2013

Background: Necrotizing pneumonia attributed to Panton-Valentine leukocidin-positive Staphylococcus aureus has mainly been reported in otherwise healthy children and young adults, with a high mortality rate. Erythroderma, airway bleeding, and leukopenia have been shown to be predictive of mortality. The objectives of this study were to define the characteristics of patients with severe leukopenia at 48-h hospitalization and to update our data regarding mortality predicting factors in a larger population than we had previously described.Methods: It was designed as a case-case study nested in a cohort study. A total of 148 cases of community-acquired, necrotizing pneumonia were included. The following data were collected: basic demographic information, medical history, signs and symptoms, radiological findings and laboratory results during the first 48 h of hospitalization. The study population was divided into 2 groups: (1) with severe leukopenia (leukocyte count ≤3,000 leukocytes/mL, n=62) and (2) without severe leukopenia (>3,000 leukocytes/mL, n=86).Results: Median age was 22 years, and the male-to-female gender ratio was 1.5. The overall in-hospital mortality rate was 41.2%. Death occurred in 75.8% of severe leukopenia cases with median survival time of 4 days, and in 16.3% of cases with leukocyte count >3,000/mL (P<0.001). Multivariate analysis indicated that the factors associated with severe leukopenia were influenza-like illness (adjusted odds ratio (aOR) 4.45, 95% CI (95% confidence interval) 1.67-11.88, P=0.003), airway bleeding (aOR 4.53, 95% CI 1.85-11.13, P=0.001) and age over 30 years (aOR 2.69, 95% CI 1.08-6.68, P=0.033). A personal history of furuncles appeared to be protective (OR 0.11, 95% CI 0.01-0.96, P=0.046).Conclusion: S. aureus-necrotizing pneumonia is still an extremely severe disease in patients with severe leukopenia. Some factors could distinguish these patients, allowing better initial identification to initiate adapted, rapid administration of appropriate therapy. © 2013 Khanafer et al.; licensee BioMed Central Ltd. Source

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