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Background Enterococcus faecalis infective endocarditis (EFIE) is characterized by a higher frequency of relapses than other infective endocarditis. The role of the treatment on its occurrence remains poorly understood. The aim of this study was to investigate whether the antibiotic regimen could impact the risk of relapse in EFIE. Materials This was a multicenter retrospective study of patients diagnosed with definite EFIE between 2015 and 2019 in 14 French hospitals. The primary endpoint was the occurrence of relapses within the year following endocarditis diagnosis. As death was a competing risk for relapse, Fine and Gray models were used for studying risk factors and impact of treatment. Results Of the 279 patients included, 83 (29.7%) received the amoxicillin-gentamicin (A-G) combination, 114 (40.9%) amoxicillin-ceftriaxone (A-C), 63 (22.6%) A-G and A-C (A-G/A-C) sequentially, 9 (3.2%) amoxicillin (A), and 10 received other treatments. One-year-relapse rate was 9.3% (26 patients). Relapse occurred after a median delay of 107 days from EFIE diagnosis; 6 occurred after 6 months, and 6 were diagnosed by blood cultures in asymptomatic patients. In multivariate analysis, surgery during treatment was a protective factor against one-year relapse and death. The cumulative incidence of relapse 1 year after endocarditis was 46.2% for patients treated with amoxicillin, 13.4% with A-G, 14.7% with A-C, and 4.3% with A-G/A-C (P ≥.05 in multivariate analysis). Conclusions Relapses after treatment of EFIE are frequent, frequently asymptomatic, and may occur more than 6 months after the initial episode. [ABSTRACT FROM AUTHOR]

Objectives: To describe the prevalence of poxtA among clinical linezolid-resistant enterococci (LRE) collected in France from 2016 to 2020 and to extensively characterize its genetic supports and environments.Methods: All LRE clinical isolates received at the National Reference Centre for Enterococci from French hospitals between 2016 and 2020 were included. LRE isolates were screened for linezolid resistance genes (cfr-like, optrA and poxtA) by real-time PCR and phenotypically characterized. A collection of 11 representative poxtA-positive isolates (10 Enterococcus faecium and 1 Enterococcus faecalis) underwent WGS by hybrid assembly combining short-read (Illumina MiSeq) and long-read (MinION) approaches. Transferability of poxtA was attempted by filter-mating experiments.Results: Out of 466 LRE received at the National Reference Centre for Enterococci over the period, 47 (10.1%) were poxtA-positive, including 42 E. faecium. The 11 isolates characterized by WGS were confirmed to be epidemiologically unrelated by core genome analysis and eight different STs were assigned to E. faecium isolates. The poxtA gene was found to be plasmid carried and flanked by IS1216E transposase genes in all isolates and frequently linked with fexB, tet(M) and tet(L). A total of seven distinct poxtA-harbouring plasmids were obtained after hybrid assembly and plasmid transfer of poxtA was successful in three cases. For the two poxtA/optrA-positive isolates, those genes were carried by different plasmids.Conclusions: The poxtA gene has been circulating among clinical enterococci in France since at least 2016, mostly in E. faecium and independently from optrA. The poxtA-carrying plasmids often co-carried resistance genes to phenicols and tetracyclines, and could have been co-selected through their veterinary use. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the novel cfr(D) gene identified in an Enterococcus faecium clinical isolate (15-307.1) collected from France.Methods: The genome of 15-307.1 was entirely sequenced using a hybrid approach combining short-read (MiSeq, Illumina) and long-read (GridION, Oxford Nanopore Technologies) technologies in order to analyse in detail the genetic support and environment of cfr(D). Transfer of linezolid resistance from 15-307.1 to E. faecium BM4107 was attempted by filter-mating experiments. The recombinant plasmid pAT29Ωcfr(D), containing cfr(D) and its own promoter, was transferred to E. faecium HM1070, Enterococcus faecalis JH2-2 and Escherichia coli AG100A.Results: As previously reported, 15-307.1 belonged to ST17 and was phenotypically resistant to linezolid (MIC, 16 mg/L), vancomycin and teicoplanin. A hybrid sequencing approach confirmed the presence of several resistance genes including vanA, optrA and cfr(D). Located on a 103 kb plasmid, cfr(D) encoded a 357 amino acid protein, which shared 64%, 64%, 48% and 51% amino acid identity with Cfr, Cfr(B), Cfr(C) and Cfr(E), respectively. Both optrA and cfr(D) were successfully co-transferred to E. faecium BM4107. When expressed in E. faecium HM1070 and E. faecalis JH2-2, pAT29Ωcfr(D) did not confer any resistance, whereas it was responsible for an expected PhLOPSA resistance phenotype in E. coli AG100A. Analysis of the genetic environment of cfr(D) showed multiple IS1216 elements, putatively involved in its mobilization.Conclusions: Cfr(D) is a novel member of the family of 23S rRNA methyltransferases. While only conferring a PhLOPSA resistance phenotype when expressed in E. coli, enterococci could constitute an unknown reservoir of cfr(D). [ABSTRACT FROM AUTHOR]

Background: The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) isolated in horse infections is not well documented, especially in France. The aim of the study was to evaluate the prevalence of MRSA isolates in horse infections from 2007 to 2013 in France and to characterize phenotypically and genotypically this collection. Results: Out of 1393 S. aureus horse isolates, 85 (6.1%) were confirmed to be MRSA. Interestingly, the prevalence of MRSA significantly increased from 2007-2009 to 2010-2013 (0.7 vs. 9.5%, P <0.0001). Resistance to methicillin was due to the presence of the mecA gene in 84 strains (98.8%) while one strain (1.2%) possessed the mecC gene. The vast majority of the strains (83/85, 97.6%) was resistant to at least three different classes of antibiotics. Multi-locus sequence typing (MLST) showed that MRSA strains belonged mainly since not all belong to two sequence types (STs): ST398 (53/85, 62.4%) and ST8 (28/85, 32.9%). It is worth to note that all ST398 MRSA isolates were detected in the period 2010-2013. Other molecular typing methods were also used, such SCCmec analysis, spa typing and rep-PCR (Diversilab, bioMérieux). All these four techniques were in good agreement, with spa typing and rep-PCR being more discriminative than MLST and SCCmec typing. Conclusions: This study is the first epidemiological study in France with extensive characterization of MRSA isolates associated with horse infections in stud farms. It shows that there is a significant increase of MRSA prevalence between 2007 and 2013, which mainly results from the spread of ST398 clones. It also highlights the importance of horses as a potential reservoir of important antimicrobial resistance genes. [ABSTRACT FROM AUTHOR]

Objectives Unprecedented outbreaks of vancomycin-resistant enterococci (VRE) have occurred in French hospitals since 2004. The aim of this study was to provide a picture of the spread and control of VRE in France and to characterize the isolates. Methods Notification of VRE cases to Institut de Veille Sanitaire has been mandatory since 2001. Isolates of VRE were sent to the National Reference Centre for species and vancomycin-resistance gene identification. Isolates were tested for antimicrobial susceptibility and typed by PFGE and multilocus sequence typing. Results Five hundred and four VRE notifications from 195 hospitals were recorded, corresponding to 2475 cases of infection (n = 243) or colonization (n = 2232) and 74 episodes of clustered cases. Outbreaks were controlled by implementation of infection control measures, although the number of new hospitals reporting isolation of VRE was increasing. The majority of 902 VRE isolated from 2006 to 2008 were Enterococcus faecium (94.8%) with the vanA or vanB gene. No isolate was resistant to linezolid, tigecycline or fusidic acid. PFGE analysis showed 161 different patterns. Generally a few predominant clones and several minor clones spread in a single hospital. In a subset of 46 representatives of PFGE clones, 13 different sequence types were characterized, all belonging to clonal complex CC17, while the esp and hyl genes were inconsistently detected. Conclusions The national mandatory notification of unusual nosocomial events allowed rapid identification of VRE outbreaks and early implementation of control measures that have proved effective. However, VRE continue to emerge in a growing number of hospitals. [ABSTRACT FROM PUBLISHER]

Species belonging to the Aerococcus genus are isolated from the urine and blood of elderly patients suffering from urinary tract infections (UTIs). However, the clinical significance, phenotypic features and antimicrobial susceptibilities of these underestimated and/or misidentified species remain unclear. From March 2006 to November 2008, among 350 non-enterococcal Streptococcaceae species isolated from urinary specimens, 30 (8.6%) Aerococcus spp. strains were recovered. All strains were characterized using a phenotypic approach (API 20 STREP, ID 32 STREP and VITEK 2 systems), 16S rRNA gene sequencing, and susceptibility to antimicrobial agents commonly used in UTIs. The average age of patients was 73 y and most of them presented with a predisposing urological disease (31%) and/or a systemic underlying condition (48%). All isolates were identified to the species level using the molecular tool (Aerococcus urinae, n = 20; Aerococcus sanguinicola, n = 8; Aerococcus viridans, n = 2), whereas the phenotypic methods were frequently unreliable. All aerococcal isolates were susceptible to amoxicillin, vancomycin, and teicoplanin and showed a low-level resistance to gentamicin. Fluoroquinolones, co-trimoxazole, and fosfomycin exhibited a variable activity. Most A. urinae isolates were resistant to co-trimoxazole and susceptible to fosfomycin, whereas all A. sanguinicola isolates were resistant to fosfomycin and susceptible to co-trimoxazole. [ABSTRACT FROM AUTHOR]

Polyphasic taxonomic analysis was performed on a novel bacterium, designated UR159T, isolated in 2016 from human blood of a septic patient hospitalized in France. Preliminary 16S rRNA gene sequence-based phylogenetic analysis indicated that strain UR159T belonged to the family Flavobacteriaceae , forming a distinct phyletic line distantly related (<94% sequence similarity) to known species of the family. Further phenotypic, chemotaxonomic and genomic analyses were performed. Cells were non-motile, oxidase-negative, catalase-positive Gram-negative rods. It was strictly aerobic yielding yellow-pigmented colonies, and was metabolically rather inert. Major fatty acids were iso-branched fatty acids, predominantly iso-C 15:0 (55.5%) and iso-C 17:1 ω 9 c (8.8%). Whole genome sequencing revealed a 2.3-Mbp genome encoding a total of 2262 putative genes with a genomic DNA G + C content at 37.6 mol%. The average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH) values between strain UR159T and the most closely related members of the Flavobacteriaceae family were <75% and <39%, respectively, much below the established cut-offs for ANI (<95–96%) and isDDH (<70%) for species and genus delineation. Average Amino Acid Identity (AAI) percentages were also estimated and were lower than 65% (cut-off proposed for genus delineation for uncultivated prokaryotes) in all cases, except for F. marinum that was just at the limit (65.1%). Based on these findings, we propose it as a new genus and species, Avrilella dinanensis gen. nov., sp. nov. (type strain UR159T = CIP 111616T = DSM 105483T). [ABSTRACT FROM AUTHOR]

• Cephalosporinase-overproducer Enterobacterales are significantly more resistant to temocillin than ESBL-producing Enterobacterales (37.7% vs 23.5%; P < 0.01); • The rate of temocillin resistance is correlated to the number of inactive beta-lactams, ranging from 3.7% to 60.0% in strain susceptible to all beta-lactams and those resistant to 3 beta-lactams; • Among third-generation cephalosporin-resistant Enterobacterales, temocillin was active against 64.9% of the strains nonsusceptible to piperacillin-tazobactam, ofloxacin, and cotrimoxazole. • In ESBL-producing strains, the rate of resistance to temocillin trend to increase from 13.9% in 2014 to 23.9% in 2017 (P < 0.01). Temocillin is used for several years in some European countries but, only since 2015 in France. We assessed the susceptibility of Enterobacterales strains isolated from blood culture 1 year before (2014) and 2 years after (2017) its use in France. 1,387 strains were included by 17 clinical laboratories located throughout France: 363 in 2014 and 1,024 in 2017. The rate of resistance to temocillin was 4.6% and 26.7% in 3rd generation cephalosporin (3GC) susceptible and resistant strains respectively. Cephalosporinase-overproducer (COPE) strains were significantly more resistant to temocillin (37.7%) than ESBL-producer (ESBL-PE) (23.5%) (P < 0.01). The rate of temocillin resistance was correlated to the number of inactive beta-lactams. The rate of resistance to temocillin trend to increase from 13.9% in 2014 to 23.9% in 2017 (P < 0.01). Temocillin remains highly active against Enterobacterales but the trend in resistance should be assessed over time. [ABSTRACT FROM AUTHOR]

Objective: To describe the characteristics, management and outcomes of hospitalised patients with Clostridioides difficile infection (CDI) treated with and without fidaxomicin., Methods: This prospective, multicentre, observational study (DAFNE) enrolled hospitalised patients with CDI, including 294 patients treated with fidaxomicin (outcomes recorded over a 3-month period) and 150 patients treated with other CDI therapies during three 1-month periods. The primary endpoint was baseline and CDI characteristics of fidaxomicin-treated patients., Results: At baseline, the fidaxomicin-treated population included immunocompromised patients (39.1%) and patients with severe (59.2%) and recurrent (36.4%) CDI. Fidaxomicin was associated with a high rate of clinical cure (92.2%) and low CDI recurrence (16.3% within 3 months). Clinical cure rates were ≥90% in patients aged ≥65 years, those receiving concomitant antibiotics and those with prior or severe CDI. There were 121/296 (40.9%) patients with adverse events (AEs), 5.4% with fidaxomicin-related AEs and 1.0% with serious fidaxomicin-related AEs. No fidaxomicin-related deaths were reported., Conclusions: Fidaxomicin is an effective and well-tolerated CDI treatment in a real-world setting in France, which included patients at high risk of adverse outcomes.Trial registration: Description of the use of fidaxomicin in hospitalised patients with documented Clostridium difficile infection and the management of these patients (DAFNE), NCT02214771, www.ClinicalTrials.gov.

Introduction. Even though Corynebacterium aurimucosum has been described in 2002, this species has long been underestimated due to the unreliability of conventional identification methods and only a few cases of infections have been reported. Hypothesis/Gap Statement. Little is known about clinical significance and antimicrobial susceptibility profile of this uncommon species. Aim. To evaluate the clinical relevance of C. aurimucosum and its antimicrobial susceptibility profile. Methodology. All C. aurimucosum isolates, collected from 2010 to 2019 in 10 French university hospitals, were retrospectively included. Demographic, clinical and microbiological data were collected for all cases. Antimicrobial susceptibility testing was performed according to the 2019 EUCAST guidelines. Results. Fifty-seven clinical isolates of C. aurimucosum were collected in 57 patients (median age, 65.8 years; male/female sex ratio, 1.1), mostly from urine (28 %), blood culture (28 %) and bone/synovial fluid (19 %) samples. Of them, 14 cases of infection were confirmed, mainly bone and joint infections (50 %) followed by urinary tract infections (UTIs) (21 %), bacteremia (14 %), skin and soft-tissue infections (14 %). C. aurimucosum was recovered in pure culture in 36 % of cases (UTIs and bacteremia) while mixed cultures were observed for other infections. By testing 52 clinical isolates in vitro , this species appeared to be fully susceptible to linezolid and vancomycin while most isolates (>80 %) were susceptible to amoxicillin (MIC 90 , 2 µg ml -1 ), gentamicin, tetracycline and rifampicin. Both cefotaxime and ciprofloxacin seemed to have a limited activity (ca. 50 % of susceptible strains). The MIC distribution for ciprofloxacin showed a bimodal profile with a population of highly-resistant strains with MICs >2 µg ml -1 . Most isolates (>90 %) were categorized as resistant to penicillin G and clindamycin. Conclusion. C. aurimucosum should be considered as an actual opportunistic pathogen, and treatment with amoxicillin, vancomycin or linezolid should be preferred.

To increase the knowledge about S. capitis in the neonatal setting, we conducted a nationwide 3-month survey in 38 neonatal intensive care units (NICUs) covering 56.6% of French NICU beds. We demonstrated 14.2% of S. capitis BSI (S.capBSI) among nosocomial BSIs. S.capBSI incidence rate was 0.59 per 1000 patient-days. A total of 55.0% of the S.capBSIs were late onset catheter-related BSIs. The S. capitis strains infected preterm babies (median gestational age 26 weeks, median birth weight 855 g). They were resistant to methicillin and aminoglycosides and belonged to the NRCS-A clone. Evolution was favorable in all but one case, following vancomycin treatment.

Antibiotic stewardship programmes (ASP) are essential to tackle antibiotic resistance. Clinical microbiologists (CMs) play a key role in these programmes; however, few studies describe their actual involvement. Our objective was to explore CMs' involvement in French hospital ASP. In 2018, we conducted a survey among CMs working in large public French hospitals (600 acute care beds or more). The questionnaire focused on the following topics: microbiology department's characteristics, hospital ASP, and CMs' involvement in this programme, including their use of rapid diagnostic tests (RDT). Fifty/74 CMs answered (response rate 68%), with 68% working in a teaching hospital. CMs were leading the ASP in 6% of cases, and 57% of hospitals had a multidisciplinary antibiotic stewardship team. Most microbiology departments (92%) were using specific PCR, processed 24/7 in 74% of hospitals. More than half (58%) were using syndromic panel-based testing, 94% mass spectrometry, and 96% immunochromatographic/colorimetric RDT. Blood cultures were processed 24/7 in 44% of hospitals. CMs were involved in this. Finally, 42% of CMs wished to be more involved in their hospital's ASP, the most frequently reported barrier being lack of time (36%). CMs should be more involved in ASP. RDT are widely used, but not implemented in an optimal way.

Objectives: This study aimed to analyse antimicrobial susceptibility evolution of equine pathogens isolated from clinical samples from 2006-2016., Methods: A collection of 25 813 bacterial isolates was studied, clustered according to their origins (respiratory tract, cutaneous, genital and other), and analysed for their antimicrobial susceptibility using the disk diffusion method., Results: The most frequently isolated pathogens were group C Streptococci (27.6%), Escherichia coli (20.0%), Staphylococcus aureus (7.8%), Pseudomonas aeruginosa (4.0%), Enterobacter spp. (3.4%), Klebsiella pneumoniae (2.4%), and Rhodococcus equi (1.8%). Of the isolates, 9512 were from respiratory samples (36.8%), 7689 from genital origin (29.8%), and 4083 from cutaneous samples (15.8%). Over the 11-year period, the frequency of multidrug-resistant (MDR) strains fluctuated between 6.4-20.4% for group C Streptococci and 17-37.7% for Klebsiella pneumoniae. From 2006-2009, 24.5-43.0% of Staphylococcus aureus isolates were MDR; after 2009 the level did not exceeded 27.6%. For Escherichia coli and Enterobacter spp., these levels were mostly >30.0% until 2012, but significantly decreased thereafter (22.5-26.3%)., Conclusions: This study is the first large-scale analysis of equine pathogens, by the number of samples and duration of study. The results showed high levels of MDR strains and the need to support veterinary antimicrobial stewardship to encourage proper use of antibiotics., (Copyright © 2019 International Society for Antimicrobial Chemotherapy. Published by Elsevier Ltd. All rights reserved.)

Objectives: To describe the epidemiological trend of linezolid-resistant enterococci (LRE) collected in France from 2006 to 2016 and to extensively characterize LRE isolates., Methods: The National Reference Center for Enterococci (NRC-Enc) received enterococcal isolates suspected to be VRE and/or LRE from all French hospitals between 2006 and 2016. LRE isolates were phenotypically characterized and their genomes were entirely sequenced by Miseq (Illumina). Transfer of linezolid resistance was attempted by filter mating experiments., Results: Out of 3974 clinical isolates of enterococci received at the NRC-Enc over the period, 9 (0.2%) were LRE (MICs 8 to >32 mg/L), including 6 Enterococcus faecium and 3 Enterococcus faecalis. This overall prevalence significantly increased over the study period, reaching 0.8% in 2016. The five LRE isolated before 2016 were vanA-positive E. faecium whereas strains isolated in 2016 (one E. faecium and three E. faecalis) were susceptible to vancomycin. None of these isolates was part of an outbreak, while E. faecium strains were assigned to four different STs [17 (1), 80 (3), 412 (1) and 650 (1)] and all three E. faecalis belonged to ST480. Except for the strain isolated in 2010, all LRE were positive for optrA, which was located on plasmids (5/8) or in the chromosome (3/8). Plasmid transfer of optrA was successful in three cases., Conclusions: There has been a significant increase in the prevalence of LRE in France over time; this is due to the spread of optrA among E. faecium and E. faecalis human clinical isolates (VRE or not)., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: The Enterobacter cloacae complex (Ecc), routinely referred to as "E. cloacae" in clinical microbiology, encompasses several species with 12 genetic clusters and one sequence crowd that can be identified based on hsp60 sequencing. Little is known about the pathogenicity and distribution of resistance to antibiotics among the Ecc., Methods and Results: In this prospective multicentre study, a total of 193 Ecc clinical isolates were collected from 10 academic hospitals distributed nationally across France and identified at the genetic cluster level on the basis of hsp60 sequencing. E. hormaechei isolates, which belong to clusters VI-VIII, were the largest group (53%), followed by cluster III that accounted for 28% of clinical isolates. All other Ecc clusters were present except cluster VII (E. hormaechei subsp. hormaechei). Cephalosporinase overproduction and ESBL were significantly more present in E. hormaechei (33% and 20%) than in other clusters (19% and 3%, respectively)., Conclusions: These results suggest that rapid identification of "E. cloacae" at the genetic cluster level could improve adequacy of empirical antibiotic treatment and reduce the unnecessary use of broad spectrum antibiotics., (Copyright © 2018 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Multiresistance in staphylococci constitutes a major challenge for the antimicrobial chemotherapy of invasive infections such as bacteraemia or bone and joint infections (BJIs). A nationwide prospective study was performed to detect antimicrobial resistance trends among staphylococci causing invasive infections. Between October 2011 and February 2012, 367 meticillin-resistant Staphylococcus aureus (MRSA) and 695 coagulase-negative staphylococci (CoNS) were collected from 37 French hospitals, mainly from bacteraemia (59.9%) and osteoarticular infections (29.0%). Minimum inhibitory concentrations (MICs) were determined by broth microdilution, and specific screening and confirmation tests were performed to detect heterogeneous vancomycin-intermediate S. aureus (hVISA). Staphylococcal isolates exhibiting a linezolid MIC>4 mg/L were further characterised to determinate their clonal relationships and the mechanism of resistance. MRSA exhibited additional resistances, including levofloxacin (82% associated resistance), gentamicin (13.6%), fusidic acid (13.6%) and rifampicin (6.5%), compromising oral step-down therapy in BJIs. Only two hVISA strains (0.5%) were identified. Among the CoNS, mainly Staphylococcus epidermidis (506/695; 72.8%), resistance to first- and second-line agents was more common. Linezolid resistance was identified in 10 CoNS (1.4%). The most frequent linezolid resistance mechanism was the G2576T mutation in 23S rDNA (9/10). For the first time in France, the cfr gene was found in five related sequence type 2 (ST2) S. epidermidis from two different hospitals, in association with ribosomal RNA and L3 ribosomal protein mutations. These national data must be considered when selecting empirical treatment for invasive staphylococcal infections. Moreover, the emergence and spread of linezolid-resistant CoNS carrying the cfr gene is of concern., (Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

To determine if hospital effluent input has an ecological impact on downstream aquatic environment, antibiotic resistance in Enterococcus spp. along a medical center-retirement home-wastewater treatment plant-river continuum in France was determined using a culture-based method. Data on antibiotic consumption among hospitalized and general populations and levels of water contamination by antibiotics were collected. All isolated enterococci were genotypically identified to the species level, tested for in vitro antibiotic susceptibility, and typed by multilocus sequence typing. The erm(B) and mef(A) (macrolide resistance) and tet(M) (tetracycline resistance) genes were detected by PCR. Along the continuum, from 89 to 98% of enterococci, according to the sampled site, were identified as Enterococcus faecium. All E. faecium isolates from hospital and retirement home effluents were multiply resistant to antibiotics, contained erm(B) and mef(A) genes, and belonged to hospital-adapted clonal complex 17 (CC17). Even though this species remained dominant in the downstream continuum, the relative proportion of CC17 isolates progressively decreased in favor of other subpopulations of E. faecium that were more diverse, less resistant to antibiotics, and devoid of the classical macrolide resistance genes and that belonged to various sequence types. Antibiotic concentrations in waters were far below the MICs for susceptible isolates. CC17 E. faecium was probably selected in the gastrointestinal tract of patients under the pressure of administered antibiotics and then excreted together with the resistance genes in waters to progressively decrease along the continuum.

Objectives: Isolation rates of unusual non-fermentative Gram-negative bacilli (i.e. other than Pseudomonas aeruginosa and Acinetobacter baumannii) are increasing but studies are limited to few observations. We aimed at determining risk factors for infection and influence of antibiotic treatment on the outcome., Methods: A six-month (December 1, 2008-May 31, 2009) prospective multicenter cohort study was conducted in nine French teaching hospitals. Characteristics of patients colonized or infected by unusual NF-GNB, adequacy of antimicrobial therapies, and outcome were analyzed., Results: Analysis of 158 patients (median age, 62.7 years) was conducted. Stenotrophomonas maltophilia was the predominant bacterial species isolated (39%) followed by Achromobacter group (15%) and non-baumannii Acinetobacter species (13%). Compared to colonized patients, infected ones were more frequently immunocompromised [relative risk (RR) = 1.63, (95% confidence interval (CI) = 1.02-2.60, P = 0.05)], hospitalized within the last three months [RR 1.67 (95% CI 1.09-2.58, P = 0.02)], admitted in an intensive care unit with central venous catheter [RR 1.74 (95% CI 1.15-2.63, P = 0.01)]. The overall hospital mortality concerned 28 patients (18%) but no association with inadequate antimicrobial treatment was found except in the group of S. maltophilia infected cases [RR 2.81 (95% CI 1.01-7.83, P = 0.02)]., Conclusion: Naturally carbapenems-resistant S. maltophilia is the main unusual NF-GNB pathogen in hospitalized patients, leading to inappropriate empirical antibiotic treatment at the time of emerging extended-spectrum β-lactamase-producing bacteria., (Copyright © 2012. Published by Elsevier Ltd.)

The aim of this study was to evaluate the prevalence of resistance to macrolide-lincosamide-streptogramin (MLS) antibiotics as well as to assess the molecular basis of this resistance amongst 72 Staphylococcus saprophyticus urinary isolates collected from 2005 to 2009 in University Hospital of Caen (France). Of the 72 strains studied, 33 (45.8%) were resistant to at least one MLS antibiotic, including 24 (72.7%) with an M phenotype, 5 (15.2%) with an inducible MLS(B) phenotype, 3 (9.1%) with a combined M+L phenotype and 1 (3.0%) with an L phenotype. All isolates were susceptible to the combination of streptogramins A and B. The resistance genes erm(A), erm(B), erm(C), msr(A) and lnu(A) were detected alone in 0, 0, 5 (15.2%), 24 (72.7%) and 1 (3.0%) of the 33 MLS-resistant isolates, respectively, whereas 2 strains (6.1%) were positive for both msr(A) and lnu(A). All msr(A)-positive isolates exhibited an M phenotype, whereas all five erm(C)-positive and all three lnu(A)-positive strains displayed, respectively, an inducible MLS(B) phenotype and an L phenotype with a positive Hodge test. Plasmid analysis indicated that erm(C) and lnu(A) genes were borne by small-size plasmids (ca. 2.5 kb), whereas larger plasmids (30-90 kb) harboured msr(A). In conclusion, these findings show a high prevalence of MLS resistance in S. saprophyticus, which was mainly associated with the presence of the msr(A) gene. Since S. saprophyticus colonises the gastrointestinal tract, it may constitute an unexpected reservoir for MLS resistance genes, in particular msr(A), amongst coagulase-negative staphylococci., (Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Objectives: To assess the in vitro susceptibility of Actinobaculum schaalii to 12 antimicrobial agents as well as to dissect the genetic basis of fluoroquinolone resistance., Methods: Forty-eight human clinical isolates of A. schaalii collected in Switzerland and France were studied. Each isolate was identified by 16S rRNA sequencing. MICs of amoxicillin, ceftriaxone, gentamicin, vancomycin, clindamycin, linezolid, ciprofloxacin, levofloxacin, moxifloxacin, co-trimoxazole, nitrofurantoin and metronidazole were determined using the Etest method. Interpretation of results was made according to EUCAST clinical breakpoints. The quinolone-resistance-determining regions (QRDRs) of gyrA and parC genes were also identified and sequence analysis was performed for all 48 strains., Results: All isolates were susceptible to amoxicillin, ceftriaxone, gentamicin, clindamycin (except three), vancomycin, linezolid and nitrofurantoin, whereas 100% and 85% were resistant to ciprofloxacin/metronidazole and co-trimoxazole, respectively. Greater than or equal to 90% of isolates were susceptible to the other tested fluoroquinolones, and only one strain was highly resistant to levofloxacin (MIC ≥32 mg/L) and moxifloxacin (MIC 8 mg/L). All isolates that were susceptible or low-level resistant to levofloxacin/moxifloxacin (n = 47) showed identical GyrA and ParC amino acid QRDR sequences. In contrast, the isolate exhibiting high-level resistance to levofloxacin and moxifloxacin possessed a unique mutation in GyrA, Ala83Val (Escherichia coli numbering), whereas no mutation was present in ParC., Conclusions: When an infection caused by A. schaalii is suspected, there is a risk of clinical failure by treating with ciprofloxacin or co-trimoxazole, and β-lactams should be preferred. In addition, acquired resistance to fluoroquinolones more active against Gram-positive bacteria is possible.

Enterococci are responsible for various community- and hospital-acquired infections. Glycopeptides (vancomycin and teicoplanin) are active against these microorganisms by inhibiting cell wall synthesis through binding to cell wall precursors. Enterococcus faecium has developed multidrug resistance, including resistance to glycopeptides. Resistance to glycopeptides is due to the acquisition of an operon of genes cooperating to synthesize precursors devoid of affinity for the glycopeptides. Outbreaks were recently reported in hospital settings. These outbreaks were due to E. faecium isolates belonging to an hospital-adapted clonal complex (CC17) characterized by high level resistance to ampicillin and fluoroquinolones and frequently containing virulence factors. Outbreaks may be controlled by appropriate measures and new antibiotics are available in therapy. However, spreading of clonal strains adapted to hospitals require close surveillance.

One hundred twenty-one extended-spectrum beta-lactamse-producing enterobacterial clinical isolates were screened for the qepA gene. A single CTX-M-15-positive Escherichia coli isolate (0.8%) that produced the putative pump QepA2 was identified. This qepA2 gene was located onto a 90-kb mobilizable plasmid that conferred reduced susceptibility to hydrophilic fluoroquinolones.

Introduction: The treatment of urinary tract infection (UTI) in women is based mainly on empirical antibiotic therapy. It requires up-to-date knowledge of the susceptibility patterns of the bacteria most commonly identified in that setting. The aim of this prospective study was to measure the antibiotic susceptibility of Escherichia coli isolates responsible for UTIs in women from a single area and to compare it in hospital and community settings., Materials and Methods: From May 2003 through April 2004, UTI was diagnosed in 1838 women around Rennes (France), 893 of them inpatients admitted to the teaching hospital and 945 outpatients in the community. We determined the susceptibility to 7 antibiotics of the resulting 1217 E. coli isolates., Results: E. coli resistance rates in hospitalized and community patients were respectively 47.9% and 39.2% for aminopenicillins, 47.3% and 25.4% for coamoxiclav, 19.2% and 14.1% for cotrimoxazole, 14.3% and 5.7% for first-generation quinolones, and 8.9% and 3.7% for fluoroquinolones. All these rates were significantly higher among hospitalized patients (p<0.05). Conversely, resistance to injectable third-generation cephalosporins and fosfomycin was similar and infrequent in both groups., Conclusion: Comparisons with previous data show that activity of third-generation cephalosporins and fosfomycin on E. coli appears unchanged, in contrast to the increased resistance rates to other antibiotics usually prescribed for UTI.

Objectives: To detect the qnrA, qnrB and qnrS genes among Salmonella isolates received at the French National Reference Centre for Salmonella in Paris, France., Methods: Antibiotic susceptibility was determined by disc diffusion for 499 Salmonella isolates including 320 Salmonella Typhimurium, 100 Salmonella Enteritidis and 79 Salmonella Hadar collected in 2002. Amplification with specific primers of qnrA, qnrB and qnrS genes was performed for all Salmonella Typhimurium, Salmonella Enteritidis and Salmonella Hadar isolates resistant to quinolones and for 17 additional isolates that produced expanded-spectrum beta-lactamases (ESBLs)., Results: Prevalence of quinolone resistance was 3.75%, 11% and 79.7% for Salmonella Typhimurium, Salmonella Enteritidis and Salmonella Hadar serovars, respectively. A single isolate (0.2%) was qnrA-positive (QnrA1 determinant) being a Salmonella serovar Concord carrying also the ESBL gene bla(CTX-M-15). This strain was probably from East Africa. No qnrB or qnrS genes were identified., Conclusions: Whereas plasmid-mediated quinolone resistance of the Qnr type is emerging in Enterobacteriaceae worldwide, it remains rare in Salmonella in France.

The species belonging to the Acinetobacter genus are currently reported as opportunistic pathogens in hospitalized patients with underlying predispositions. However, except for the Acinetobacter calcoaceticus-Acinetobacter baumannii complex, the identification of other species is frequently unreliable, especially for Acinetobacter ursingii and Acinetobacter schindleri, newly described in 2001. Thus, the clinical significance, phenotypic features, and antimicrobial susceptibilities of these two misidentified species remain unclear. Of 456 Acinetobacter sp. clinical strains isolated from 2002 to 2005 in Henri Mondor Hospital, 15 isolates (10 A. ursingii and 5 A. schindleri isolates) were studied. They were characterized using a phenotypic approach (API 20 NE and VITEK 2 systems), 16S rRNA gene sequencing, and susceptibility to antimicrobial agents with evaluation of impact in clinical relevance. The two corresponding type strains were also included for comparison. All isolates were identified to the species level using molecular tools, whereas the phenotypic methods remained unreliable due to the absence of these two species in the manufacturers' databases. However, the API 20 NE system appeared to be a reasonably reliable phenotypic alternative for the identification of A. ursingii when the numerical code 0000071 was found. Conversely, no discriminative phenotypic alternative existed for A. schindleri isolates. Concerning antimicrobial susceptibility, A. ursingii strains appeared to be more resistant to antibiotics than A. schindleri strains, which could imply therapeutic consequences. Finally, the prevalence of infections caused by A. ursingii and A. schindleri (representing 9.7% and 4.8% of non-A. calcoaceticus-A. baumannii complex strains, respectively) seems to be underestimated.