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The full identification and susceptibility profile of staphylococci from positive blood cultures (BCs) generally takes 24-48 h using phenotypic methods. The aim of this prospective study was to evaluate the clinical impact of a real-time PCR strategy for rapid identification of staphylococci and determination of methicillin resistance directly from positive BCs. During a 12-month period, 250 episodes of positive BCs with organism morphology resembling staphylococci were enrolled. Two strategies were compared: conventional (n = 128) using standard phenotypic methods or rapid (n = 122) using a real-time PCR assay that is able to detect specific genes of Staphylococcus aureus (nuc and sa442) and the encoding gene for methicillin resistance (mecA). Overall, 97 episodes (39%) were clinical-significant bloodstream infections. The prevalence of methicillin resistance of S. aureus was 24%. A favorable outcome (defined as clinical cure with resolution of signs and no evidence of recurrence or relapse at 12 weeks follow-up) was observed in similar proportions of episodes with (58%) or without (60%) PCR testing (p 0.8). In multivariate analyses, age and infection due to methicillin-susceptible S. aureus (adjusted OR 0.96, 95% CI 0.93-0.99; and adjusted OR 3.11, 95% CI 1.12-8.65, respectively) were the unique factors independently associated with a favorable outcome. Among the 153 episodes of contaminated BCs, similar proportions received unjustified antibiotic therapy (PCR strategy: 17%, conventional testing: 10%; p 0.33). In a setting with a moderate level of methicillin-resistant S. aureus and relatively high contamination of BCs, real-time PCR testing was not beneficial compared to conventional methods. [ABSTRACT FROM AUTHOR]

The full identification and susceptibility profile of staphylococci from positive blood cultures (BCs) generally takes 24-48 h using phenotypic methods. The aim of this prospective study was to evaluate the clinical impact of a real-time PCR strategy for rapid identification of staphylococci and determination of methicillin resistance directly from positive BCs. During a 12-month period, 250 episodes of positive BCs with organism morphology resembling staphylococci were enrolled. Two strategies were compared: conventional (n = 128) using standard phenotypic methods or rapid (n = 122) using a real-time PCR assay that is able to detect specific genes of Staphylococcus aureus (nuc and sa442) and the encoding gene for methicillin resistance (mecA). Overall, 97 episodes (39%) were clinical-significant bloodstream infections. The prevalence of methicillin resistance of S. aureus was 24%. A favorable outcome (defined as clinical cure with resolution of signs and no evidence of recurrence or relapse at 12 weeks follow-up) was observed in similar proportions of episodes with (58%) or without (60%) PCR testing (p 0.8). In multivariate analyses, age and infection due to methicillin-susceptible S. aureus (adjusted OR 0.96, 95% CI 0.93-0.99; and adjusted OR 3.11, 95% CI 1.12-8.65, respectively) were the unique factors independently associated with a favorable outcome. Among the 153 episodes of contaminated BCs, similar proportions received unjustified antibiotic therapy (PCR strategy: 17%, conventional testing: 10%; p 0.33). In a setting with a moderate level of methicillin-resistant S. aureus and relatively high contamination of BCs, real-time PCR testing was not beneficial compared to conventional methods. [ABSTRACT FROM AUTHOR]

Abstract: There is a constant need for new antibacterial agents because of the unavoidable development of bacterial resistance that follows the introduction of antibiotics in clinical practice. As observed in many fields, innovation generally comes by series. For instance, a wide variety of broad-spectrum antibacterial agents became available between the 1970s and the 1990s, such as cephalosporins, penicillin/β-lactamase inhibitor combinations, carbapenems, and fluoroquinolones. Over the last 2 decades, the arrival of new antibacterial drugs on the market has dramatically slowed, leaving a frequent gap between isolation of resistant pathogens and effective treatment options. In fact, many pharmaceutical companies focused on the development of narrow-spectrum antibiotics targeted at multidrug-resistant Gram-positive bacteria (e.g. methicillin-resistant Staphylococcus aureus, penicillinresistant Streptococcus pneumoniae, and vancomycin-resistant Enterococcus faecium). Therefore, multidrug-resistant Gram-negative bacteria (e.g. extended-spectrum β-lactamase-producing Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii) recently emerged and rapidly spread worldwide. Even if some molecules were developed, new molecules for infections caused by these multidrug-resistant Gram-negative bacteria remain remarkably scarce compared to those for Gram-positive infections. This review summarises the major microbiological, pharmacological, and clinical properties of systemic antibiotics recently marketed in France (i.e. linezolid, daptomycin, tigecycline, ertapenem, and doripenem) as well as those of antibacterial drugs currently in development (i.e. ceftobiprole, ceftaroline, dalbavancin, telavancin, oritavancin, iclaprim, and ramoplanin) or available in other countries (i.e. garenoxacin, sitafloxacin, and temocillin). [Copyright &y& Elsevier]

Abstract: Aim: The aim of this study was to determine the antimicrobial susceptibilities of Clostridium difficile clinical isolates obtained from symptomatic patients suffering from diarrhoea. Methods: In vitro activities of 22 antimicrobial agents were evaluated against 401 clinical isolates of C. difficile collected from patients hospitalized in a French university hospital (Henri Mondor hospital) between 2001 and 2007. The in vitro antibiotic susceptibility testing was performed using the disc diffusion method according to recommendations of the antibiogram committee of the French society for microbiology. Results: All strains were found to be susceptible to metronidazole and vancomycin but resistant to clindamycin, gentamicin, and colistin. Most of them were susceptible to pristinamycin (97.8%), rifampin (94.8%), and chloramphenicol (97.3%), and variable degrees of resistance were found for erythromycin and spiramycin (72.8%), as well as for tetracycline (85.6%). Note that none of the strain was susceptible to ofloxacin, and that 80.5% of them showed a high-level resistance. For β-lactams, all strains were resistant to tested cephalosporins, and nine isolates (2.2%) were also resistant to penicillins combined or not to a β-lactamase inhibitor. Finally, 28 (7%) and 38 (9.5%) of tested strains were categorized intermediate and resistant to imipenem (with a heterogeneous aspect), respectively. Conclusion: All tested strains were found to be susceptible to metronidazole and vancomycin which remain antimicrobial agents for the treatment of infections caused by C. difficile. [Copyright &y& Elsevier]

We searched for plasmid-mediated quinolone resistance determinants of the Qnr type in several water samples collected at diverse locations from the Seine River (Paris, France). The qnrS2 genes were identified from Aeromonas punctata subsp. punctata and A. media. The qnrS2 gene was located on IncU-type plasmids in both isolates, which resulted in increased MIC values of quinolones and fluoroquinolones, once they were transferred into Escherichia coli. The qnrS2 gene identified in A. punctata was part of novel genetic structure corresponding to a mobile insertion cassette element. This identification of plasmid-mediated qnr genes outside Enterobacteriaceae underlines a possible diffusion of those resistance determinants within gram-negative rods. [ABSTRACT FROM AUTHOR]

Plasmid-mediated quinolone resistance is being reported increasingly worldwide among isolates of enterobacteria. This resistance is mostly associated with Qnr-like determinants that confer resistance to quinolones, e.g., nalidixic acid, and reduced susceptibility to fluoroquinolones. This study investigated whether amino-acid substitutions in QnrA1 and QnrS1 determinants might be responsible for an enhancement of resistance to quinolones and, particularly, to fluoroquinolones. However, random and site-directed mutagenesis failed to identify any single amino-acid substitution that could be responsible for higher levels of resistance to quinolones or fluoroquinolones, indicating that the selection of such mutants in vivo is probably a rare event. [ABSTRACT FROM AUTHOR]

Although resistance to quinolones is commonly chromosomally-encoded in Enterobacteriaceae, the emergence of plasmid-mediated quinolone resistance (PMQR) has also been reported, with at least three known resistance mechanisms to date, i.e., Qnr, aminoglycoside acetyltransferase AAC(6′)-Ib-cr and QepA. Qnr proteins protect target enzymes (DNA gyrase and type IV topoisomerase) from quinolone inhibition, the AAC(6′)-Ib-cr enzyme acetylates norfloxacin and ciprofloxacin, and the QepA efflux pump extrudes hydrophilic fluoroquinolones. Although these PMQR determinants confer only low-level resistance to quinolones and/or fluoroquinolones, they may provide a favourable background in which the selection of additional chromosomally-encoded quinolone resistance mechanisms can occur. [ABSTRACT FROM AUTHOR]

Background The Hajj is the largest annual mass gathering event in the world, thus favoring the transmission of various infections: 183 different nationalities, high temperatures, coincidence with the start of the flu season in the Northern hemisphere, a long barefoot walk, tent-type accommodation, communal toilet facilities, absence of food control, and sharing of razors. Infections are the first cause of hospital admission, which often occurs in the home country of pilgrims. Methods Literature review on PubMed from 1952 to November 2015 on the epidemiology and prevention of infections contracted during the Hajj, using the keywords “Hajj” and “infections”. Results Respiratory tract infections, ENT infections, influenza, pyogenic pneumonia, whooping cough, and tuberculosis are most frequently observed during the Hajj. Outbreaks of meningococcal meningitis have been reported in pilgrims and their contacts. Waterborne infections such as gastroenteritis and hepatitis A are common, despite the improvement of health conditions. Pyoderma and furuncles are also frequently observed. Recently, dengue fever, Alkhumra hemorrhagic fever, and Rift Valley fever have emerged but no case of MERS-coronavirus, appeared in Saudi Arabia in 2012, have yet been observed during the 2012–2014 Hajj. Conclusion Prevention is based on compulsory meningococcal vaccination, vaccination against seasonal influenza and pneumococcal infections for pilgrims at high risk of contracting the infection, and on vaccination against hepatitis A. Updating immunization for diphtheria/tetanus / poliomyelitis/pertussis and measles/mumps is also crucial and pilgrims must comply with hygiene precautions. [ABSTRACT FROM AUTHOR]

Even if Panton-Valentine leukocidin (PVL), toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxins (SEB and SEC), and exfoliative toxins (ETA and ETB) may be associated with severe infections, the clinical significance of their presence in clinical isolates of Staphylococcus aureus remains poorly documented. In this study, we evaluated the prevalence of toxin genes and the relationship between their presence and the severity of infection. We screened for the presence of these six toxin genes among 186 consecutive S. aureus clinical isolates (resistant or not to methicillin) during a two-month period. We compared the toxin gene profile between strains recovered from patients presenting uncomplicated infections ( n = 151) and from patients suffering from severe infections ( n = 35). At least one toxin gene was detected in 55 (29.6%) isolates as follows: pvl ( n = 1), tst + sec ( n = 5), seb ( n = 19), seb + sec ( n = 1), sec ( n = 28), and eta ( n = 1). The proportion of toxin-producing strains among patients with uncomplicated infections (27.8%) and patients with severe infections (37.1%) was not statistically different ( p = 0.3044), even if the severity of infection tended to be associated with the presence of sec ( p = 0.0655). Although the prevalence of toxin genes was relatively high herein, no statistically significant association between the severity of infection and the presence of toxin genes was observed. [ABSTRACT FROM AUTHOR]

Rapid diagnostic tests (RDTs) for infectious diseases, with a turnaround time of less than 2 hours, are promising tools that could improve patient care, antimicrobial stewardship and infection prevention in the emergency department (ED) setting. Numerous RDTs have been developed, although not necessarily for the ED environment. Their successful implementation in the ED relies on their performance and impact on patient management. The aim of this narrative review was to provide an overview of currently available RDTs for infectious diseases in the ED. PubMed was searched through August 2019 for available studies on RDTs for infectious diseases. Inclusion criteria included: commercial tests approved by the US Food and Drug Administration (FDA) or Conformité Européenne (CE) in vitro diagnostic devices with data on clinical samples, ability to run on fully automated systems and result delivery within 2 hours. A nonexhaustive list of representative commercially available FDA- or CE-approved assays was categorized by clinical syndrome: pharyngitis and upper respiratory tract infection, lower respiratory tract infection, gastrointestinal infection, meningitis and encephalitis, fever in returning travellers and sexually transmitted infection, including HIV. The performance of tests was described on the basis of clinical validation studies. Further, their impact on clinical outcomes and anti-infective use was discussed with a focus on ED-based studies. Clinicians should be familiar with the distinctive features of each RDT and individual performance characteristics for each target. Their integration into ED work flow should be preplanned considering local constraints of given settings. Additional clinical studies are needed to further evaluate their clinical effectiveness and cost-effectiveness. [ABSTRACT FROM AUTHOR]

• This article presents the most recent data (2018) on the epidemiology of emerging extensively drug-resistant bacteria (eXDR) in France, alongside the control measures implemented in hospitals, from two complementary sources: external nosocomial infection notifications and the National Reference Centre for antibiotic resistance. This report shows the constant increase in the annual number of eXDR bacteria identified in France since 2012. This 2018 report of Healthcare-Associated Infections Early Warning and Response System (HAI-EWRS) notifications of carbapenemase-producing Enterobacteriaceae (CPE) or glycopeptide-resistant Enterococcus faecium (GRE), and of strains analysed by the National Reference Center for anti-microbial resistance (NRC) aimed to describe the epidemiology of emerging extensively drug-resistant bacteria (eXDR) in France and control measures implemented in hospital settings. All HAI-EWRS notifications of eXDR received at the national level and all eXDR strains received at the NRC between January 1, 2018 and January 31, 2018 were analysed. Variables analysed were number of cases, number of strains, resistance mechanism, sample type, link with a foreign country, and control measures implemented. In 2018, 1704 CPE notifications and 315 GRE notifications were reported in France, with an increasing trend since 2012 (× 6 for CPE, × 3 for GRE), from respectively 364 and 155 hospitals (+66% for CPE, +57% for GRE since 2012). eXDR strains were mainly isolated from rectal screening swabs. Notifications with patients receiving standard precautions were more often associated with outbreaks than notifications with patients receiving contact precautions at admission. NRC received 2674 CPE strains and 775 GRE strains in 2018 (× 8.3 and × 2.8 compared with 2012). The increasing annual number of eXDR notifications and eXDR strains received by the NRC is multifactorial but reflects a worrying spread of eXDR in France. The number of infections remains low, but this article shows that existing recommendations are not fully implemented. [ABSTRACT FROM AUTHOR]

• Viridans group Streptococci is the most common Streptococci involved in infective endocarditis (IE). • Minimum inhibitory concentration (MIC) for amoxicillin between 0.25 and 2 mg/L is associated with mortality. • Cardiac surgery for IE is the only protective factor. A variety of microorganisms can cause infective endocarditis (IE), with Staphylococci and Streptococci accounting for the majority of cases. Streptococci are a common cause of community-acquired IE but few studies have focused on this subgroup of endocarditis. A retrospective multicentre study was conducted between 2012 and 2017 in 12 hospital centres in France. Data were extracted from the local diagnosis-related group database and matched with microbiological results. After identification, the records were retrospectively analysed. A total of 414 patients with streptococcal endocarditis were included. The patients were predominantly male (72.8%) and the median age was 73.2 years (interquartile range [IQR] 61.3-80.9). The majority of patients (70.6%) had native valve endocarditis. Embolic complications were seen in 38.8% of patients. Viridans group Streptococci (VGS) and bovis-equinus group Streptococci (BGS) accounted for 52.4% and 34.5% of isolated strains, respectively. Minimum inhibitory concentrations (MICs) of amoxicillin were <0.125, 0.125-2 and >2 mg/L for 59.6%, 27% and 1% of isolates, respectively. In-hospital mortality for patients with Streptococci -related IE was 17.8%. In multivariate analysis, the only factor associated with in-hospital mortality was MIC for amoxicillin between 0.25 and 2 mg/L (P = 0.04; OR = 2.23 [95% confidence interval (CI) 1.03-4.88]) whereas performance of cardiac surgery for IE was a protective factor (P = 0.001, OR = 0.23 [95% CI 0.1-0.56]). IE remains a serious and deadly disease despite recent advances in diagnosis and treatment. Adaptation of antibiotic doses to MICs for amoxicillin and surgery may improve patient outcome. [ABSTRACT FROM AUTHOR]

Abstract Background Our current understanding of the pathophysiology and management of sepsis is associated with a lack of progress in clinical trials, which partly reflects insufficient appreciation of the heterogeneity of this syndrome. Consequently, more patient-specific approaches to treatment should be explored. Aims To summarize the current evidence on precision medicine in sepsis, with an emphasis on translation from theory to clinical practice. A secondary objective is to develop a framework enclosing recommendations on management and priorities for further research. Sources A global search strategy was performed in the MEDLINE database through the PubMed search engine (last search December 2017). No restrictions of study design, time, or language were imposed. Content The focus of this Position Paper is on the interplay between therapies, pathogens, and the host. Regarding the pathogen, microbiologic diagnostic approaches (such as blood cultures (BCs) and rapid diagnostic tests (RDTs)) are discussed, as well as targeted antibiotic treatment. Other topics include the disruption of host immune system and the use of biomarkers in sepsis management, patient stratification, and future clinical trial design. Lastly, personalized antibiotic treatment and stewardship are addressed (Fig. 1). Implications A road map provides recommendations and future perspectives. RDTs and identifying drug-response phenotypes are clear challenges. The next step will be the implementation of precision medicine to sepsis management, based on theranostic methodology. This highly individualized approach will be essential for the design of novel clinical trials and improvement of care pathways. [ABSTRACT FROM AUTHOR]

Introduction Les méningites lymphocytaires sont fréquentes et d’étiologies variées : infectieuses, dysimmunitaires, immunoallergiques et carcinologiques. Il n’existe pas de consensus sur le bilan étiologique initial. L’objectif de ce travail est de décrire les étiologies documentées en se basant sur une stratégie diagnostique en 3 étapes, avec réalisation d’un suivi à distance. Matériels et méthodes Étude prospective, observationnelle, multicentrique, dans 2 CHU et 1 CHG, d’adultes présentant une méningite lymphocytaire avec ou sans encéphalite, de février 2015 à février 2016. Les cas, hospitalisés, étaient repérés par le microbiologiste et signalés à l’investigateur. Une stratégie diagnostique en trois étapes était proposée au médecin en charge du patient. Un suivi téléphonique ou sur dossier était réalisé à un an. Les étiologies infectieuses ont été classées en possibles, probables ou certaines. Résultats Au total, 41 patients ont été inclus dont 15 méningo-encéphalites. Une étiologie a été documentée dans 66 % des cas. Les méningites et méningo-encéphalites étaient respectivement infectieuses (66 % et 40 %), non infectieuses (8 % et 20 %) et non documentées (31 % et 40 %). Le bilan diagnostique de première intention (PCR HSV-VZV et entérovirus dans le LCR) a permis de faire 11 diagnostics (deux infections à HSV, deux à VZV, sept à entérovirus). Celui de deuxième intention 12 diagnostics : deux tuberculoses, deux VIH, deux lymphomes (un certain, un suspecté), une sarcoïdose ; un entérovirus, un VRS et une grippe A probables (PCR nasale) ; une leptospirose et une infection à M. pneumoniae possibles. Le bilan de troisième intention a permis seulement le diagnostic d’une hépatite E aiguë. Tous les patients ont eu le bilan de première intention. Malgré les recommandations de l’infectiologue, le taux de réalisation des bilans de seconde et troisième intention est resté sous optimal : 14 cas sont restés sans étiologie dont neuf n’ayant eu que le bilan de première intention, et deux que celui de deuxième intention. Trois patients sont restés sans diagnostic au terme du bilan complet. Trois étiologies ont été déterminées en dehors du bilan suggéré : une possible tularémie, une encéphalite d’ Hashimoto, une méningite iatrogène. Aucun diagnostic supplémentaire n’a été fait à un an du suivi. Conclusion Le taux d’élucidation diagnostique observé (66 %) est similaire aux études rétrospectives publiées malgré la suggestion d’un bilan étiologique. Cependant, celui-ci n’a été réalisé de façon complète que chez cinq des 14 patients restés sans diagnostic. La réalisation du bilan de première et deuxième intention proposé a permis un diagnostic chez 56 % des patients et pourrait donc être réalisé de manière plus large. Cinq pour cent des patients présentaient une infection VIH, ce qui incite à intégrer ce test dès le bilan de première intention. [ABSTRACT FROM AUTHOR]

Background: Alternative therapeutic regimens are urgently needed against carbapenemase-producing Enterobacteriaceae. Fosfomycin often remains active against KPC and OXA-48 producers, but emergence of resistance is a major limitation. Our aim was to determine whether the association of temocillin with fosfomycin might be useful to treat KPC- or OXA-48-producing Escherichia coli infections.Methods: Isogenic derivatives of E. coli CFT073 with blaKPC-3- or blaOXA-48-harbouring plasmids (named CFT073-KPC-3 and CFT073-OXA-48, respectively) were used. The addition of temocillin to fosfomycin was tested using the chequerboard method and time-kill curves as well as in a fatal peritonitis murine model. Mice were treated for 24 h with fosfomycin alone or in combination with temocillin. Bacterial loads, before and after treatment, were determined in the peritoneal fluid and fosfomycin-resistant mutants were detected.Results: Temocillin MICs were 8, 32 and 256 mg/L for CFT073 (WT), CFT073-KPC-3 and CFT073-OXA-48, respectively. Fosfomycin MIC was 0.5 mg/L for all strains. The chequerboard experiments demonstrated synergy for all three strains. In time-kill curves, combining temocillin with fosfomycin was synergistic, bactericidal and prevented emergence of resistance for CFT073-pTOPO and CFT073-KPC-3, but not CFT073-OXA-48. In vivo, for the three strains, bacterial counts were lower in peritoneal fluid with the combination compared with fosfomycin alone (P < 0.001) and inhibited growth of resistant mutants in all cases.Conclusions: The combination of fosfomycin and temocillin demonstrated a benefit in vitro and in vivo against E. coli strains producing KPC-3 or OXA-48-type carbapenemases. This combination prevented the emergence of fosfomycin resistance and proved to be more bactericidal than fosfomycin alone. [ABSTRACT FROM AUTHOR]

Although carbapenemase-producing Enterobacteriaceae (CPE) have become a serious public health issue, their detection remains challenging. The aim of this study was to implement a test based on imipenem hydrolysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS), using 65 strains producing or not a carbapenemase. Then, we compared its performance to that of the Rapidec Carba NP test using 20 additional strains. The MS-based test effectively discriminated between CPE and other non-carbapenem-susceptible strains compared to the Rapidec Carba NP test (sensitivity 100% and 92%, specificity 94% and 92%, respectively). The MS-based test gave less difficulty in interpretation than the colorimetric Rapidec Carba NP test. MALDI-ToF gave a result in less than one hour and limited the use of expensive molecular assays. In conclusion, the hydrolysis test based on MALDI-ToF MS can detect clinically relevant CPE isolates in routine practice. This technology, also described to screen for carbapenem resistance in Pseudomonas aeruginosa and Acinetobacter baumannii complex strains, also seems to be interesting in routine practice for these pathogens. [ABSTRACT FROM AUTHOR]

This study describes the clinical and microbiological features associated with group B Streptococcus (GBS) bone and joint infections (BJIs). It was a retrospective analysis of adult cases of GBS BJIs reported to the French National Reference Center for Streptococci from January 2004 to December 2014. Clinical data and GBS molecular characteristics are reported. Strains were collected from 163 patients. The most frequent comorbidities were: solid organ cancer ( n = 21, 21%) and diabetes mellitus ( n = 20, 20%). The main infection sites were knee (47/155 = 30%) and hip (43/155 = 27%), and occurred on orthopedic devices in 71/148 cases (48%). CPS III ( n = 47, 29%), Ia ( n = 26, 16%) and V ( n = 40, 25%) were predominant. Resistance to erythromycin, clindamycin and tetracycline was detected in 55/163 (34%), 35/163 (21%) and 132/163 (81%) strains, respectively. The most frequent sequence types were ST-1 ( n = 21, 25%), ST-17 ( n = 17, 20%) and ST-23 ( n = 11, 13%). The rate of resistance to erythromycin was 0% for ST-17 strains, 52% ( n = 11) for ST-1 and 44% ( n = 7) for ST-23 ( p < 0.001). GBS bone and joint infections predominantly occur in patients aged >50 years and/or with comorbidities such as cancer and diabetes mellitus. CPS type distribution and MLST are very similar to that of other adult GBS invasive infections. [ABSTRACT FROM AUTHOR]

Objective Although urinary tract infections are the second leading cause of infections among patients aged above 65 years, data on bacterial epidemiology of urinary specimens in these patients is scarce. Our aim was to describe the main bacterial species found at significant levels in urine specimens of the elderly and to determine their antimicrobial resistance profiles. Methods From October 2012 to October 2015, all urinary specimens (catheter-related or not) received at the laboratory of microbiology of the university hospital of Caen (France) were retrospectively studied. Results were compared to those of urinary specimens of patients aged 18–64 years. Bacterial identification was performed using MALDI-TOF mass spectrometry and antimicrobial susceptibility testing was performed as per CA-SFM guidelines. Results Out of 33,302 urine cytobacteriological examinations (UCBE) performed in patients aged above 65 years, 13,450 microorganisms were identified. Escherichia coli was the most frequent species (41.8%) followed by Enterococcus faecalis (9.7%), Pseudomonas aeruginosa (5.7%), Proteus mirabilis (4.6%), and Klebsiella pneumoniae (4.2%). Around 9% of E. coli isolates were resistant to third-generation cephalosporins, including 8.2% by production of extended-spectrum β-lactamase (ESBL). This prevalence was significantly higher than that observed in urinary specimens of patients aged 18–74 years (4.9%, P < 0.001). Conclusion The bacterial epidemiology of urines collected from the elderly is diverse and significantly different from that of urine specimens of younger patients, with a higher proportion of multidrug-resistant bacteria (particularly ESBL-producing E. coli ). [ABSTRACT FROM AUTHOR]

Introduction Les bactériémies à Vibrio cholerae non-O1, non-O139 (BVCN), plus rares que les gastro-entérites, otites, infections de plaie, sont mal connues. Après description d’un cas avec abcès hépatiques contracté au Sénégal, sans comorbidité, d’évolution favorable, nous avons réalisé une revue de la littérature consacrée aux BVCN. Patients et méthodes Revue de la littérature recensée par Pubmed utilisant les mots « Vibrio cholerae non-O1 » et « bacteremia », depuis le premier cas de 1974 jusqu’à novembre 2014. Résultats Un patient de 70 ans était hospitalisé en avril 2010 au retour du Sénégal pour diarrhée aqueuse fébrile. Ses antécédents comprenaient une hypertension, un syndrome coronarien aigu, une hépatite A 60 ans auparavant et une cholécystectomie. Le jour de son retour, le patient présentait une diarrhée aqueuse fébrile avec frissons, vomissements et douleurs abdominales. L’examen clinique ne mettait en évidence qu’une sensibilité abdominale prédominant en hypocondre droit. La biologie révélait une CRP à 397 mg/L, une hyperleucocytose à 13 000/mm 3 , ainsi qu’une cytolyse et une cholestase modérées. L’échographie abdominale, confirmée par un scanner abdominal, découvrait 2 abcès hépatiques de 3 à 5 cm. Les hémocultures revenaient positives à V. cholerae . La coproculture était négative. Après 2 mois de céftriaxone relayée par ciprofloxacine, l’évolution était favorable avec obtention de l’apyrexie, normalisation de la biologie et disparition des abcès. Après inclusion de notre cas, 350 BVCN chez 347 patients ont été analysées. Les BVCN ont contractées majoritairement été contractées à Taiwan (156, 45 %) ou aux États-Unis (60, 20 %), avec seulement 12 cas Français dont 4 importés, d’Afrique. Elles affectaient surtout des hommes (161, 77 %), de 56 ans en médiane (60 heures–88 ans), avec ≥ 1 facteur favorisant (216, 96 %) : cirrhose (122, 54 %), hémopathie-néoplasie (48, 21 %), alcoolisme (36, 16 %) ou diabète (31, 14 %). Une consommation de fruits de mer/poisson (48, 54 %), un contact avec l’eau contaminée (27, 30 %) étaient volontiers incriminés quand une source était citée (89, 25 %). Les BVCN se manifestaient par une hypo/hyperthermie (172, 76 %), une diarrhée (94, 42 %), des douleurs abdominales (89, 40 %). Un abcès hépatique n’a été rapporté que 5 fois. La mortalité était élevée (77, 33 %). En l’absence d’essais thérapeutiques, une bithérapie était souvent proposée associant une céphalosporine de 3 e génération et une cycline/fluoroquinolone pendant 14 jours, à moduler selon l’antibiogramme, le terrain et la sévérité. Conclusion Les infections à VCN, favorisées par le réchauffement climatique, l’anthropisation du milieu littoral, le commerce international de fruits de mer, la consommation de fruits de mer peu cuits et l’augmentation des populations à risque, risquent de devenir un problème de santé publique, particulièrement redoutable pour les personnes immunodéprimées. [ABSTRACT FROM AUTHOR]

Background: Outcome of patients with streptococcal prosthetic joint infections (PJIs) is not well known. Methods: We performed a retrospective multicenter cohort study that involved patients with total hip/knee prosthetic joint (THP/TKP) infections due to Streptococcus spp. from 2001 through 2009. Results: Ninety-five streptococcal PJI episodes (50 THP and 45 TKP) in 87 patients of mean age 69.1 ± 13.7 years met the inclusion criteria. In all, 55 out of 95 cases (57.9 %) were treated with debridement and retention of the infected implants with antibiotic therapy (DAIR). Rifampicin-combinations, including with levofloxacin, were used in 52 (54.7 %) and 28 (29.5 %) cases, respectively. After a mean follow-up period of 895 days (IQR: 395-1649), the remission rate was 70.5 % (67/95). Patients with PJIs due to S. agalactiae failed in the same proportion as in the other patients (10/37 (27.1 %) versus 19/58 (32.7 %); p = .55). In the univariate analysis, antibiotic monotherapy, DAIR, antibiotic treatments other than rifampicin-combinations, and TKP were all associated with a worse outcome. The only independent variable significantly associated with the patients' outcomes was the location of the prosthesis (i.e., hip versus knee) (OR = 0.19; 95 % CI 0.04-0.93; p value 0.04). Conclusions: The prognosis of streptococcal PJIs may not be as good as previously reported, especially for patients with an infected total knee arthroplasty. Rifampicin combinations, especially with levofloxacin, appear to be suitable antibiotic regimens for these patients. [ABSTRACT FROM AUTHOR]

Objectives: Temocillin is a 6-α-methoxy derivative of ticarcillin that shows in vitro activity against Enterobacteriaceae producing Klebsiella pneumoniae carbapenemase (KPC). Our objective was to assess in vivo temocillin activity against KPC-producing Escherichia coli.Methods: Isogenic derivatives of the WT E. coli CFT073 producing KPC-2, KPC-3 or OXA-48 were constructed. An experimental murine model of intra-abdominal infection with sepsis was used. Mice were treated subcutaneously with temocillin 200 mg/kg every 2 h for 24 h, reproducing the duration of time that the free serum concentration of temocillin exceeded the MIC in humans with a regimen of 2 g every 12 h or 2 g every 8 h. Blood, peritoneal fluid (PF) and spleen were collected; 24 h survival and sterility rates were assessed.Results: Temocillin MICs were 8, 16, 32, and 256 mg/L for the susceptible strain and KPC-2-, KPC-3-, and OXA-48-producing strains, respectively. In mice treated with temocillin, significant bacterial reduction was obtained in PF, blood, and spleen for the susceptible strain and KPC-2- and KPC-3-producing strains (P < 0.001) but not for the OXA-48-producing strain. Sterility rates in PF were 53%, 10%, 0% and 0% (P < 0.001) and sterility rates in blood were 77%, 40%, 3% and 0% (P < 0.001), while survival rates were 97%, 97%, 57%, 0% (P < 0.001) for mice infected with the susceptible strain and KPC-2-, KPC-3- and OXA-48-producing strains, respectively.Conclusions: In a lethal-infection model with bacteraemia from intra-abdominal origin, temocillin retained significant activity in PF, blood and spleen and prevented death in mice by effectively working against KPC-producing E. coli with temocillin MICs ≤16 mg/L. [ABSTRACT FROM AUTHOR]

Thanks to the recent advent of matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) technology, Helcococcus kunzii is now easily identifiable and considered as an opportunistic pathogen. However, data about antimicrobial susceptibilities remain very limited. The aim of the study was, then, to assess its in vitro susceptibility to 18 antimicrobial agents and to investigate the genetic basis of macrolide and tetracycline resistance. Thirty-nine human clinical isolates of H. kunzii collected from 2008 to 2013 were studied, as well as the type strain ATCC 51366. Minimum inhibitory concentrations (MICs) of penicillin G, amoxicillin, cefotaxime, imipenem, gentamicin, erythromycin, clindamycin, quinupristin-dalfopristin, ciprofloxacin, levofloxacin, tetracycline, tigecycline, vancomycin, teicoplanin, linezolid, daptomycin, cotrimoxazole and rifampin were determined by the microdilution method. Screening for macrolide [ erm(A) including erm(TR), erm(B), erm(C), erm(F), erm(T), erm(X), msr(A) and mef(A)] and tetracycline [ tet(L), tet(M) and tet(O)] resistance genes was performed, as well as the detection of mutations in 23S rRNA. Except for one strain resistant to cefotaxime, all strains were categorised as susceptible to β-lactams, glycopeptides, linezolid, daptomycin and tigecycline. Whereas ciprofloxacin and gentamicin exhibited limited activity, 95 % of strains were categorised as susceptible to levofloxacin. Concerning erythromycin, a bimodal distribution was observed, with 29 'wild-type' strains (MICs from 0.25 to 2 mg/L) and 11 'resistant' strains (MICs ≥256 mg/L), including ten harbouring erm(TR). Two isolates exhibited acquired tetracycline resistance (MICs of 16 mg/L) by the production of tet(M). This large study on the in vitro antimicrobial susceptibility of H. kunzii suggests that β-lactams (especially penicillins) should be preferred for the treatment. [ABSTRACT FROM AUTHOR]

Objectives The primary objective of our study was to obtain susceptibility data for josamycin against Streptococcus pyogenes isolated from patients presenting with upper respiratory tract infections in France. The secondary objective was to characterize the molecular mechanism of resistance in macrolide-resistant isolates. Patients and methods MICs of erythromycin, clarithromycin, azithromycin, josamycin, and clindamycin were determined by the broth microdilution method. Resistance genes erm (B), erm (TR), and mef (A) were screened by PCR. Results The MIC 50 and MIC 90 of josamycin against 193 isolates of S. pyogenes were 0.12 and 0.25 mg/L, respectively, with a resistance rate estimated at 4.7%. Resistance was due to the erm (B) gene whereas strains harboring erm (TR) or mef (A) remained susceptible. Conclusions Josamycin was active against >95% of S. pyogenes isolated from patients with upper respiratory tract infections, and can be used as an alternative for the treatment of pharyngitis. [ABSTRACT FROM AUTHOR]

Purpose We determined the prevalence of ESBL Enterobacteriaceae in urinary tract infections among inpatients, identified risk factors of acquisition, and evaluated the effectiveness of alternatives to carbapenems. Methods The clinical, microbiological, and therapeutic data as well as the outcomes were recorded for all ESBL-E positive urine samples for three months. Results Thirty-one (4%) of the 762 Enterobacteriaceae positive cultures were ESBL producers. The predisposing conditions for being infected with those strains were: immunodepression (61%), recent hospitalization (52%), recent antibiotic therapy (52%), and urinary catheterization (61%). 19% of infections were community acquired. The seven cases of acute pyelonephritis and five of prostatitis were treated with piperacillin-tazobactam (5), fluoroquinolones (4), ceftazidime (2), or carbapenems (only 1) after specialized advice. Four (33%) patients relapsed at week 10: three were immunodepressed and three presented with bacteremia. Conclusions Alternatives to carbapenems (especially piperacillin-tazobactam) seem to be a good option for non-bacteremic UTI in immunocompetent patients. [ABSTRACT FROM AUTHOR]

Detection of microorganisms by blood cultures (BCs) is essential in managing patients with bacteraemia. Rather than the number of punctures, the volume of blood drawn is considered paramount in efficient and reliable detection of microorganisms. We performed a 1-year prospective multicentre study in adult emergency departments of three French university hospitals comparing two methods for BCs: a unique blood culture (UBC) collecting a large volume of blood (40 mL) and the standard method of multiple blood cultures (MBC). The performances of both methods for bacterial contamination and efficient microbial detection were compared, each patient serving as his own control. Amongst the 2314 patients included, three hundred were positive for pathogens ( n = 245) or contaminants ( n = 55). Out of the 245 patients, 11 were positive for pathogens by UBC but negative by MBC and seven negative by UBC but positive by MBC (p 0.480). In the subgroup of 137 patients with only two BCs, UBC was superior to MBC (p 0.044). Seven and 17 patients had contaminated BCs by UBC and MBC only, respectively (p 0.062). Considering the sums of pathogens missed and contaminants, UBC significantly outperformed MBC (p 0.045). Considering the complete picture of cost savings, efficient detection of microorganisms and decrease in contaminations, UBC offers an interesting alternative to MBC. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Given the increasing frequency of cefotaxime-resistant strains, third-generation cephalosporins (3GC e.g. cefotaxime, ceftriaxone) might not be recommended any longer as empirical antibiotic therapy for community-acquired Gram-negative bacteremia (CA-GNB). Patients and methods: We conducted a multicenter prospective descriptive study including patients with CA-GNB. Results: Two hundred and nineteen patients were included. Escherichia coli and Pseudomonas aeruginosa were the most frequently isolated species in 63% (n =138) and 11% (n =24) of the cases, respectively. The prevalence of cefotaxime-resistance reached 18% (n =39) mostly due to intrinsic resistance (27 cases, 12%). The presence of invasive material (P <0.001), the origin of the patient (Paris region or West of France) (P =0.006), and home health care (P <0.001) were variables predicting resistant GNB. The negative predictive value for resistance in patients with invasive material coming from the West of France, or without invasive material and with home health care was 94%. The positive predictive value for patients with invasive material living in Paris, or without invasive material and with home health care only reached 58 and 54%, respectively. Conclusions: Using 3GC for CA-GNB due to cefotaxime-resistant strains was relatively frequent, ESBL-producing Enterobacteriaceae being rarely involved. Our study highlights the role of local epidemiology; before any changes to first-line antibiotic therapy, local epidemiological data should be taken into account. [Copyright &y& Elsevier]

Nonfermenting Gram-negative bacilli (NF-GNB) are ubiquitous environmental opportunistic bacteria frequently misidentified by conventional phenotypic methods. The aim of this study was to determine the distribution of NF-GNB species by 16 S rRNA gene sequencing (used as reference method) and to compare performances of biochemical tests and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). From nine French hospitals, 188 NF-GNB isolates (except P. aeruginosa and A. baumannii) were prospectively collected from 187 clinical samples between December 2008 and May 2009. By using the genotypic approach, 173 (92%) and 188 (100%) isolates were identified to the species and genus level, respectively. They covered 35 species and 20 genera, with a predominance of Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Pseudomonas putida group bacteria. Of the 173 species-level identified strains, concordant identification to the species-level was obtained for 75.1%, 83% and 88.9% of isolates with API 20 NE strip, the VITEK-2 (ID-GN card) system and MALDI-TOF-MS, respectively. By excluding S. maltophilia isolates accurately identified by the three methods, genus-level identification was much higher for MALDI-TOF-MS (92.9%), compared with API 20 NE and VITEK-2 (76.2% and 80.8%, respectively). In conclusion, MALDI-TOF-MS represents a rapid, inexpensive, and accurate tool for routine identification of NF-GNB in human clinical samples. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of this study was to determine the in vitro activity of six new antimicrobial agents against glycopeptide-resistant enterococci (GRE) strains from France. Methods: Sixty epidemiologically unrelated clinical isolates of Enterococcus faecium (vanA or vanB), received at the National Reference Centre for Enterococci (CNR-Enc) between 2006 and 2008, were studied. The MICs of the following antibiotics were determined by broth microdilution according to Antibiogram Committee of the French Society for Microbiology (CA-SFM) guidelines: quinupristin-dalfopristin (Q-D), linezolid (LZD), daptomycin (DPT), tigecycline (TGC), ceftobiprole (CFT), and telavancin (TLV). Strains were classified using clinical breakpoints recommended by the CA-SFM (Q-D, LZD, TGC), or the Clinical and Laboratory Standards Institute (DPT). Results: All strains were susceptible to LZD and DPT (MIC90, 4 and 2μg/ml, respectively) and only a single strain presented intermediate susceptibility to tigecycline (MIC90, 0.25μg/ml). Thirty percent of strains were resistant to Q-D (MIC90, 4μg/ml), and CFT was constantly inactive (MIC90, 64μg/ml). Finally, TLV showed low-level MICs (MIC90, 0.5μg/ml) against vanB-positive isolates but not against vanA-positive isolates (MIC90, 8μg/ml). Conclusion: Although several antibiotics are still active against GRE, it is essential to maintain an active antimicrobial resistance surveillance for these microorganisms considered as a model of multidrug resistance with a potential to transfer resistance to other bacterial species (e.g. Staphylococcus aureus). [Copyright &y& Elsevier]

A letter to editor is presented regarding a 3-year prospective study about Actinobaculum schaalii (A. schaalii ), a facultative anaerobic Gram-positive rod-shaped bacteria, in a 1602-bed hospital.

Abstract: Aim of the study: Diagnosis of Clostridium difficile-associated diarrhea is classically based on detection of toxin A and/or toxins A+B by using several techniques. However, these techniques show important differences in terms of sensitivity and specificity. In this work, we compared three commercial immunoenzymatic tests for detecting C. difficile toxins. Methods: We used three immunoenzymatic techniques: ELISA Premier™ Toxins A and B (Meridian), ImmunoCard ® (IC) Toxins A and B (Meridian), and Triage® (TRI) Antigen GDH and Toxin A (Biosite). Culture on the specific media C. difficile (bioMérieux) was performed in parallel. Results: During two years, 898 stool specimens have been tested by using the three different techniques. According to the manufacturer’s recommendations (sample positive if optical density [OD] value greater or equal to 0.15), 205 (22.8%) were positive for ELISA. Among them, 65 (31.7%) were negative for all other tests, and they have been considered as false-positive results. This discrepancy led us to choose other OD values (greater than 0.75: positive result; 0.15–0.75: limit result). For limit results, IC, TRI, antigen GDH, and culture methods were positive in 30, 2, 41, and 29% of cases, respectively, whereas for positive results (>0.75), they were positive in 82, 54, 84, and 76% of cases, respectively. Conclusion: ELISA and IC tests are the most powerful and are concordant together if interpretation is performed with OD values redefined by the microbiology laboratory. The choice of the technique to use depends on the number of samples to analyze, the rapidity of the result, and the cost. [Copyright &y& Elsevier]

Abstract: Aim of the study. – To assess the prevalence of the novel plasmid-mediated resistance to quinolones in enterobacteria isolated in our hospital. Materials and methods. – We have screened 737 enterobacterial strains isolated in Henri-Mondor hospital between 2002 and 2005 for the presence of the qnr gene by PCR using specific primers. Among them, 282 had a phenotype in concordance with extended spectrum betalactamase (ESBL). Qnr-positive strains were phenotypically and genetically characterized, and epidemiological link between the cases was investigated. Results. – Five qnr+ strains were described. The global prevalence was 0.7% but 5/282 among ESBL producing strains and 0/437 among quinolone-resistant enterobacteria non producing ESBL. The sequences of the PCR products were identical to qnrA in the environment of the integron In36. All the strains harboured also the ESBL SHV-12 gene. Tranfer of qnr by conjugaison raised quinolone MICs from 2 to 24 times. However clinical strains harboured a higher level of quinolone resistance and harboured also DNA gyrase and topoisomerase IV mutations. Two strains were epidemiologically related by molecular typing and contact tracing revealed that the patients have been previously hospitalized in the same tertiary care center. Conclusion. – We described the first investigation of qnr-positive strains in one hospital in France over 4 years. Although the qnr gene prevalence is low, nosocomial transmission is already shown and the transfer of the qnr containing integron among ESBL producing strains may predict future epidemic. Surveillance will be necessary to confirm this low prevalence rate of qnr in France. [Copyright &y& Elsevier]

La culture bactérienne est toujours le « gold standard » pour le diagnostic des infections respiratoires basses (IRB) avec un rendu final, au mieux, dans un délai de 48–72 h. Le panel syndromique Filmarray® Pneumonia Panel plus (FA-PP) permet la détection simultanée de 18 bactéries dont 15 avec une semi-quantification (en copies d'ADN/mL), 9 virus et 7 déterminants de résistance dans un délai rapide (environ 1 h). L'objectif de l'étude a été d'évaluer les performances du FA-PP par rapport à celles de la culture. Cette étude a été menée dans 11 centres, entre juillet et décembre 2018. Les prélèvements respiratoires (expectorations, aspirations endotrachéales [AET] et lavages broncho-alvéolaires [LBA]), ont été prospectivement inclus par les microbiologistes et/ou cliniciens. Parallèlement aux techniques conventionnelles (culture semi-quantitative [en UFC/mL], identification, antibiogramme), un test FA-PP (kit « Research Use Only ») a été réalisé. Un total de 515 échantillons a été inclus : 58 expectorations, 217 AET et 240 LBA, prélevés principalement chez des adultes (93,8 %) et des patients en réanimation (87,8 %). Les principales bactéries retrouvées par les 2 approches étaient : Staphylococcus aureus (n = 146), les Enterobacteriaceae (n = 135), Haemophilus influenzae (n = 106) et Pseudomonas aeruginosa (n = 59). Le FA-PP a retrouvé la majorité des bactéries qui poussaient en culture (94 %, 374/397) en plus de détecter 294 cibles bactériennes supplémentaires dans 194 échantillons. La culture standard a permis d'identifier des bactéries hors panel : Citrobacter spp. (n = 10), Stenotrophomonas maltophilia , Hafnia alvei et Morganella morganii (n = 9 pour chacune). Le rendu semi-quantitatif était au moins égal à celui de la culture dans 88 % des cas, avec une surestimation (+ 1 à 2 log 10) fréquente avec le FA-PP. La concordance du FA-PP était de 68 % pour les β-lactamases à spectre étendu et de 59 % pour la méticillino-résistance. Plusieurs patients étaient positifs pour Legionella pneumophila (n = 4) et Mycoplasma pneumoniae (n = 4), tous confirmés par les méthodes standards. Le FA-PP a aussi retrouvé 81 virus dans 76 prélèvements dont 71 % de co-infections bactériennes. Avec un rendu rapide et d'excellentes performances qualitatives, le FA-PP est un outil complémentaire à la culture pour le diagnostic des IRB sévères. Le FA-PP surestimant la semi-quantification en copies d'ADN/mL (pour lesquelles il n'y a pas de seuils de significativité) par rapport à la culture en UFC/mL, son interprétation impose un dialogue clinicobiologique pour l'adaptation précoce de l'antibiothérapie. L'impact clinique et le rapport coût–efficacité sont en cours d'évaluation. [ABSTRACT FROM AUTHOR]

The article discusses a study on the possible role of integrons in Actinotignum schaalii antimicrobial resistance. Topics covered include the resistance of the strain designated LIM87 to sulfamethoxazole and co-trimoxazole, finding on genomic sequencing of Actinotignum schaalii LIM87 with Illumina technology, and main discrepancies with TN610 in LIM87.

Introduction Les infections à gonocoque sont en recrudescence en France, ainsi que le nombre de souches résistantes aux antibiotiques. L’objectif de cette étude est de caractériser la population infectée par le gonocoque, les principales formes cliniques, la prévalence actuelle de la résistance, ainsi que les modalités et la qualité de la prise en charge des patients. Matériels et méthodes Il s’agit d’une étude observationnelle multicentrique rétrospective. Elle reprend les cas d’infections à gonocoque, diagnostiquées par PCR Neisseria gonorrhoeae positive, documentées au sein des hôpitaux et des laboratoires de villes participant au réseau sentinelle biologique RENAGO dans les départements d’Ille et Vilaine et du Morbihan. La description des cas repose sur un recueil standardisé de données cliniques et biologiques. Résultats Du 1 er janvier 2014 au 31 décembre 2016, 245 dossiers de patients présentant une infection à gonocoque ont été étudiés. L’âge médian était de 25 ans avec un sex-ratio de 1,55 Hommes/Femmes. Les principaux lieux de recrutement étaient les Cabinets de médecine générale pour 122 patients, les Urgences gynécologiques pour 45 patientes et les Services d’accueil-urgences pour 17 patients. Les infections diagnostiquées ont été : urétrite ( n = 59), infection génitale haute ( n = 40), cervicite ( n = 12), ano-rectite ( n = 11), arthrite ( n = 4), forme asymptomatique ( n = 3), orchyépididymite ( n = 2), endocardite ( n = 1), conjonctivite ( n = 1) et pyélonéphrite ( n = 1). La prévalence de la co-infection VIH était de 3,3 % (8/245), celle de Chlamydia trachomatis de 16,3 % (40/245). La culture était positive à N. gonorrhoeae chez 60 % (147/245) des patients. La Concentration minimale inhibitrice (CMI) de ceftriaxone était < 0,12 mg/L dans 99,4 % (154/155) des cas. Dans un cas, elle était considérée comme résistante à la ceftriaxone avec une CMI > 0,12 mg/L. Au total, 98,1 % (158/161) des souches étaient sensibles à la cefixime avec une CMI de cefixime < 0,12 mg/L. L’analyse des traitements prescrits montre que 70,2 % (52/74) des patients ont bénéficié d’un traitement actif et 59,5 % (44/74) d’un traitement adapté aux recommandations actuelles. Conclusion Cette étude montre la place importante du médecin généraliste dans la prise en charge des infections à gonocoque, dont la progression reste préoccupante. Le risque d’émergence de résistances nécessite la poursuite de la surveillance microbiologique, pour s’assurer que les recommandations thérapeutiques restent adaptées à l’épidémiologie nationale. [ABSTRACT FROM AUTHOR]

Introduction Devant l’émergence d’ E. coli producteurs de carbapénémases (EPC), des alternatives thérapeutiques sont nécessaires. La fosfomycine peut garder une activité sur certaines EPC de type KPC, mais s’accompagne en monothérapie de l’émergence de mutants résistants. L’objectif a été de déterminer s’il existe un bénéfice à associer la témocilline à la fosfomycine sur des souches EPC-KPC, notamment pour limiter l’émergence de mutants. Matériels et méthodes Trois variants isogéniques de la souche clinique uropathogène E. coli CFT073 ont été utilisés : avec un plasmide vide (pTOPO), un plasmide exprimant la carbapénémase KPC-3 et un plasmide OXA-48. Une synergie in vitro a été recherchée par la technique de l’échiquier et en cinétique de bactéricidie, et in vivo, dans un modèle murin de péritonite. Les souris ont été traitées pendant 24 h par fosfomycine seule ou en association avec la témocilline. Les critères de jugement étaient le nombre de bactéries viables dans le liquide péritonéal, la sélection de mutants à la fosfomycine et le taux de survie. Résultats La CMI de la témocilline était de 8 mg/L pour CFT073-pTOPO, 32 mg/L pour CFT073-KPC-3 et 256 mg/L pour CFT073-OXA-48. La CMI de la fosfomycine était 0,5 mg/L pour toutes les souches. L’association observée in vitro était synergique en bactériostase pour les 3 souches et en bactéricidie pour CFT073-pTOPO et CFT073-KPC3, et prévenait toujours l’émergence de mutants résistants à la fosfomycine. In vivo, l’ajout de la témocilline réduisait de façon significative le nombre de bactéries viables dans le liquide péritonéal pour les 3 souches en comparaison à la fosfomycine seule ( p < 0,001). Sous fosfomycine seule, des mutants résistants à la fosfomycine ont été sélectionnés chez 36 %, 27 % et 50 % des souris infectées par CFT073-pTOPO, CFT073-KPC-3 et CFT073-OXA-48 respectivement, mais dans aucun cas avec l’association ( p = 0,04, p = 0,09 et p = 0,027, respectivement). Les taux de survie étaient de 87 % et 93 % sous fosfomycine seule pour KPC-3 et OXA-48 et de 93 % et 100 % sous bithérapie (NS). Conclusion L’association de la fosfomycine à la témocilline a démontré un bénéfice in vitro et in vivo contre les souches de E. coli produisant des carbapénémases de type KPC-3 ou OXA48. Cette association prévient l’émergence de mutants résistants à la fosfomycine et s’est révélée plus bactéricide que la fosfomycine seule. [ABSTRACT FROM AUTHOR]

Introduction La fosfomycine [Fos] est indiquée en première intention dans les cystites non compliquées, et largement utilisée. Malgré la fréquence élevée de mutants résistants sélectionnés spontanément in vitro, la prévalence de la résistance à la Fos parmi les souches de E coli isolées d’infections urinaires reste très faible. Ces données paradoxales pourraient s’expliquer par un coût biologique de la résistance à la Fos. Matériels et méthodes Trois groupes de souches de E. coli ont été étudiés : 2 groupes d’isolats cliniques respectivement de phénotype multi-sensible et multi-résistant, et un groupe avec la souche E. coli CFT073 et des dérivés isogéniques résistants à la Fos sélectionnés in vitro. Les CMI de la Fos ont été déterminées par microdilution en présence de 25 mg/L de glucose-6-phosphate. Les gènes habituellement impliqués dans la résistance à la Fos (murA, glpT, uhpT, cyaA, ptsI et uhpA) ont été séquencés et la recherche du gène fosA3 a été réalisée par PCR. Dix-huit gènes de virulence représentatifs des principales souches de E. coli uropathogènes ont été recherchés par PCR. Le fitness des souches a été évalué in vitro par réalisation de courbes de croissance et mesure du taux de croissance maximal. In vivo, nous avons étudié le taux d’infection dans un modèle murin de pyélonéphrite par voie ascendante. La virulence était définie par un taux de souris infectées supérieur à 60 %. Résultats Les CMI de la Fos des souches variaient de 0,5 à plus de 1024 mg/L. Différentes mutations ont été retrouvées parmi les souches cliniques dans les gènes glpT, uhpT, cyaA et ptsI, y compris chez des souches considérées comme sensibles mais avec des CMI de la Fos entre 8 et 32 mg/L. Au contraire, certaines souches résistantes ne présentaient aucune mutation dans les gènes habituellement impliqués et séquencés dans notre étude. In vivo, il a été observé que les souches résistantes à la Fos avaient une diminution significative de 27,7 à 39,1 % ( p < 0,03) de leur capacité à produire une pyélonéphrite chez la souris, tant pour les souches cliniques multi-sensibles ou multi-résistantes que pour les mutants obtenus in vitro. Les souches sensibles à la Fos testées in vivo étaient toutes virulentes (13/13), tandis que les souches résistantes étaient soit virulentes (2/7) soit non virulentes ( p < 0,002). Cette différence ne s’expliquait pas par le nombre de facteurs de virulence, similaire entre les souches sensibles ou résistantes ( p > 0,9) et n’était pas prédite par la seule mesure du taux de croissance maximal in vitro. Conclusion La résistance à la Fos est associée à une perte de virulence des souches de E. coli in vivo dans un modèle murin de pyélonéphrite ascendante, quel que soit le groupe de souches étudié, et ce même pour des souches considérées comme sensibles mais présentant des CMI de la Fos à 8 mg/L et plus. Cette perte de virulence peut être atténuée chez certaines souches résistantes par l’acquisition probable de mutations compensatrices générant le risque de souches résistantes et virulentes. Par ailleurs, nos résultats suggèrent l’existence de mécanismes de résistance à la Fos encore inconnus. [ABSTRACT FROM AUTHOR]

Introduction La daptomycine apparaît comme un antibiotique de première ligne dans le traitement de l’endocardite infectieuse [EI] à entérocoques résistants à la vancomycine. De fortes doses sont nécessaires, mais les posologies optimales, notamment pour traiter les souches d’ Enterococcus faecium ayant une CMI proche du seuil de sensibilité (4 mg/L), ne sont pas connues. Matériels et méthodes Dans un modèle expérimental d’EI chez le lapin, des posologies équivalentes à 8 et 12 mg/kg (DAP8 et DAP12) ont été testées sur des souches d’E. faecium ayant des CMI de la daptomycine à 2 (souche Aus0004) et 4 mg/L (Mut4, mutant obtenu in vitro). Les numérations bactériennes des végétations ont été comparées entre les différents groupes de traitement. Nous avons ensuite estimé l’émergence de mutants résistants sur des milieux additionnés de daptomycine. Résultats Pour la souche Aus0004, DAP8 et DAP12 permettaient de réduire significativement la charge bactérienne des végétations par rapport au groupe contrôle (6,05 et 2,15 vs 9,14 log10 CFU/g respectivement, p < 0,001). DAP12 permettait de stériliser les végétations avec une diminution de la charge bactérienne significativement plus importante qu’avec DAP8 ( p < 0,001). Pour Mut4, une diminution significative de la charge bactérienne des végétations était également obtenue avec DAP8 et DAP12 par rapport au groupe contrôle (7,7 et 6,95 vs. 9,59 log10 CFU/g respectivement, p < 0,001). En revanche aucune différence significative n’était observée entre les 2 posologies ( p > 0,999) et aucune ne permettait de stériliser les végétations. Avec DAP8, 8,3 % des végétations infectées par Aus0004 et 63,6 % des végétations infectées par Mut4 présentaient des mutants résistants. Avec DAP12, 77,8 % des végétations infectées par Mut4 présentaient des mutants résistants. Conclusion Une posologie de 12 mg/kg semble la plus adaptée dans le traitement des EI à E. faecium ayant une CMI de la daptomycine à 2 mg/L. Dans le traitement des EI dues à une souche ayant une CMI à 4 mg/L, la daptomycine en monothérapie entraîne l’émergence de résistance. Une réévaluation de la concentration critique de sensibilité à la daptomycine pour les entérocoques semble nécessaire. [ABSTRACT FROM AUTHOR]

Background: Outcome of patients with streptococcal prosthetic joint infections (PJIs) is not well known.Methods: We performed a retrospective multicenter cohort study that involved patients with total hip/knee prosthetic joint (THP/TKP) infections due to Streptococcus spp. from 2001 through 2009.Results: Ninety-five streptococcal PJI episodes (50 THP and 45 TKP) in 87 patients of mean age 69.1 ± 13.7 years met the inclusion criteria. In all, 55 out of 95 cases (57.9 %) were treated with debridement and retention of the infected implants with antibiotic therapy (DAIR). Rifampicin-combinations, including with levofloxacin, were used in 52 (54.7 %) and 28 (29.5 %) cases, respectively. After a mean follow-up period of 895 days (IQR: 395-1649), the remission rate was 70.5 % (67/95). Patients with PJIs due to S. agalactiae failed in the same proportion as in the other patients (10/37 (27.1 %) versus 19/58 (32.7 %); p = .55). In the univariate analysis, antibiotic monotherapy, DAIR, antibiotic treatments other than rifampicin-combinations, and TKP were all associated with a worse outcome. The only independent variable significantly associated with the patients' outcomes was the location of the prosthesis (i.e., hip versus knee) (OR = 0.19; 95 % CI 0.04-0.93; p value 0.04).Conclusions: The prognosis of streptococcal PJIs may not be as good as previously reported, especially for patients with an infected total knee arthroplasty. Rifampicin combinations, especially with levofloxacin, appear to be suitable antibiotic regimens for these patients. [ABSTRACT FROM AUTHOR]

Observation: Un patient de 53 ans sans antécédent était hospitalisé pour un état de choc cardiogénique sur occlusion de la coronaire droite. Lors de son admission, 5 hémocultures (HC) étaient été prélevées. Son évolution était rapidement défavorable en réanimation avec un tableau de défaillance multiviscérale, et le patient décédait 3 jours après. Une bactérie évoquant un spirochète était détectée dans 4 HC anaérobies le lendemain. Une subculture était obtenue en 72 h sur gélose au sang en anaérobiose. Phénotypiquement, les seuls tests biochimiques positifs étaient l’oxydase et l’hippurate. L’antibiogramme montrait que la souche était résistante aux pénicillines avec une activité restaurée par les inhibiteurs de β-lactamases. Elle était aussi sensible aux céphalosporines de 3e génération, à l’imipénème et au métronidazole. L’identification définitive de Brachyspira pilosicoli a été obtenue après séquençage du gène de l’ARNr 16S. Discussion: B. (anc. Serpulina) pilosicoli est un spirochète anaérobie qui colonise le colon des animaux (dont l’homme). Il est notamment l’agent responsable de la spirochétose intestinale du porc. Même si la prévalence de la colonisation digestive par B. pilosicoli a été estimée à 10-30 % dans certaines populations (aborigènes australiens, homosexuels, VIH+), les cas rapportés de bactériémies restent rarissimes. Seuls 8 cas de bactériémies isolées ont été décrits en France (6), aux États-Unis (1) et en Grèce (1) correspondant à des patients immunodéprimés ou très graves. Dans notre cas, il s’agit d’une septicémie avec un tableau clinique très sévère probablement avec translocation digestive secondaire au choc cardiogénique. En raison de la croissance lente de ces germes dans les HC (≥ 4 j), ces bactériémies sont difficilement détectables empêchant un traitement adapté précoce. [Copyright &y& Elsevier]