Inventory of Extended-Spectrum-ß-Lactamase-Producing Enterobacteriaceae in France as Assessed by a Multicenter Study.

The objective of this study was to perform an inventory of the extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae isolates responsible for infections in French hospitals and to assess the mechanisms associated with ESBL diffusion. A total of 200 nonredundant ESBL-producing Enterobacteriaceae strains isolated from clinical samples were collected during a multicenter study performed in 18 representative French hospitals. Antibiotic resistance genes were identified by PCR and sequencing experiments. The clonal relatedness between isolates was investigated by the use of the DiversiLab system. ESBL-encoding plasmids were compared by PCR-based replicon typing and plasmid multilocus sequence typing. CTX-M-15, CTX-M-1, CTX-M-14, and SHV-12 were the most prevalent ESBLs (8% to 46.5%). The three CTX-M-type EBSLs were significantly observed in Escherichia coli (37.1%, 24.2%, and 21.8%, respectively), and CTX-M-15 was the predominant ESBL in Klebsiella pneumoniae (81.1%). SHV-12 was associated with ESBL-encoding Enterobacter cloacae strains (37.9%). qnrB, aac(6')-Ib-cr, and aac(3)-II genes were the main plasmid-mediated resistance genes, with prevalences ranging between 19.5% and 45% according to the ESBL results. Molecular typing did not identify wide clonal diffusion. Plasmid analysis suggested the diffusion of low numbers of ESBL-encoding plasmids, especially in K. pneumoniae and E. cloacae However, the ESBL-encoding genes were observed in different plasmid replicons according to the bacterial species. The prevalences of ESBL subtypes differ according to the Enterobacteriaceae species. Plasmid spread is a key determinant of this epidemiology, and the link observed between the ESBL-encoding plasmids and the bacterial host explains the differences observed in the Enterobacteriaceae species.

Appropriateness of aminoglycoside prescriptions in a French university hospital.

INTRODUCTION: Aminoglycosides are a major class of antibiotics. Their use is particularly interesting in the treatment of severe infections but their toxicity is well known. They are mostly prescribed combined with other agents and as first-line treatments. We aimed to assess the appropriateness of aminoglycoside prescriptions in a French university hospital on the basis of the latest French recommendations published in 2011. METHOD: We conducted a prospective study between January 17th and February 4th, 2014 to assess prescription modalities of aminoglycosides on the basis of the following criteria: indication, duration of treatment, dosing schedule, administration modalities, and drug level monitoring. Prescriptions were then compared to the 2011 national guidelines. RESULTS: A total of 68 consecutive prescriptions were analyzed and only 47.8% complied with guidelines. Most physicians complied with recommendations, particularly with the indication for severe infections (95.6%), the administration of a single daily dose (92.6%), and the slow intravenous infusion (30minutes) administration (84%). However, physicians tended to prescribe lower doses than recommended (40.3%), especially to patients presenting with renal insufficiency, and drug level monitoring was not optimal. CONCLUSION: Although new and accurate national recommendations were recently published, aminoglycoside prescription is still not optimal, in particular for dosing and plasma concentration monitoring.

Decline in antibiotic resistance and changes in the serotype distribution of Streptococcus pneumoniae isolates from children with acute otitis media; a 2001-2011 survey by the French Pneumococcal Network.

Streptococcus pneumoniae is an important cause of acute otitis media (AOM). The aim of this study was to evaluate trends in antibiotic resistance and circulating serotypes of pneumococci isolated from middle ear fluid of French children with AOM during the period 2001-2011, before and after the introduction of the PCV-7 (2003) and PCV-13 (2010) vaccines. Between 2001 and 2011 the French pneumococcal surveillance network analysed the antibiotic susceptibility of 6683 S. pneumoniae isolated from children with AOM, of which 1569 were serotyped. We observed a significant overall increase in antibiotic susceptibility. Respective resistance (I+R) rates in 2001 and 2011 were 76.9% and 57.3% for penicillin, 43.0% and 29.8% for amoxicillin, and 28.6% and 13.0% for cefotaxime. We also found a marked reduction in vaccine serotypes after PCV-7 implementation, from 63.0% in 2001 to 13.2% in 2011, while the incidence of the additional six serotypes included in PCV-13 increased during the same period, with a particularly high proportion of 19A isolates. The proportion of some non-PCV-13 serotypes also increased between 2001 and 2011, especially 15A and 23A. Before PCV-7 implementation, most (70.8%) penicillin non-susceptible pneumococci belonged to PCV-7 serotypes, whereas in 2011, 56.8% of penicillin non-susceptible pneumococci belonged to serotype 19A. Between 2001 and 2011, antibiotic resistance among pneumococci responsible for AOM in France fell markedly, and PCV-7 serotypes were replaced by non-PCV-7 serotypes, especially 19A. We are continuing to assess the impact of PCV-13, introduced in France in 2010, on pneumococcal serotype circulation and antibiotic resistance.

Diagnosis and management of nocardiosis after bone marrow stem cell transplantation in adults: lack of lymphocyte recovery as a major contributing factor.

Hematopoietic cell transplantation (HCT) is a curative treatment for hematological malignancies. This therapeutic approach is associated with a profound immune deficiency and an increased rate of opportunistic infections. Nocardiosis is a rare bacterial infection occurring mainly in patients with deficient cell-mediated immunity, such as AIDS patients or transplant recipients. Diagnosis of nocardiosis can be challenging, as signs and symptoms are non-specific. Routine prophylaxis with trimethoprin/sulfamethoxazole (TMP/SMZ) does not prevent the risk of infection. Between May 2001 and December 2009, five cases of nocardiosis were diagnosed from the 366 allogeneic HCT recipients in our centre. Four patients developed a disseminated nocardiosis within the first year after HCT. The fifth patient presented a localized cutaneous nocardiosis. In disseminated cases, median total CD4+ T-cells were below 100 cells/µL. Naive CD4+ CD45RA+/RO- T-cells were almost undetectable. CD8(+) T-cells and NK cells were below the normal range and CD19+ B-cell reconstitution was completely deficient. In a localized case, we observed a lack of naive thymic emigrants CD4+ CD45RA+/RO- T-cells.

Streptococcus bovis/Streptococcus equinus complex fecal carriage, colorectal carcinoma, and infective endocarditis: a new appraisal of a complex connection.

The proportion of group D streptococcal infective endocarditis (IE) (predominantly due to Streptococcus gallolyticus) and the incidence of colorectal cancer are higher in France than in most European countries. We assumed that this could be explained by a high group D streptococci (GDS) fecal carriage rate. The aims of this study were to re-assess the GDS fecal carriage rate in France and its relationship with colorectal cancer. Consecutive adult subjects who were to undergo a complete colonoscopy were invited to participate. GDS were searched in subjects' stools before their colonoscopy using biomolecular techniques. Colonoscopic findings were sorted into four subgroups: normal colonoscopy, non-tumoral lesions, benign tumors, and premalignant/malignant tumors. GDS fecal carriages were calculated overall and in each subgroup and compared. The data from 259 subjects were analyzed. GDS were identified in the feces of 12 subjects, with the following distribution: S. lutetiensis (n = 9), S. pasteurianus (n = 2), and S. gallolyticus (n = 1). This accounted for an overall GDS fecal carriage rate of 4.6 %. The GDS fecal carriage rate was 6 % in case of normal colonoscopy, 1.3 % in case of non-tumoral lesions, 3.2 % in case of benign tumors, and 11 % in case of premalignant/malignant tumors. These four percentages were not statistically different. The GDS fecal carriage rate was lower than expected, which did not confirm our working hypothesis. Most strains belonged to S. bovis biotype II, while S. gallolyticus was found only once. These findings suggest that different GDS play different roles in the etiopathogenesis of IE and colorectal cancer.

Appropriate use of carbapenems in the Besançon university hospital.

INTRODUCTION: The excessive and inappropriate use of carbapenems is responsible for the development of resistance. The scientific community has been requiring caution and using these agents in specific cases only. OBJECTIVES: The authors had for aim to evaluate the appropriate use of carbapenems in a French university hospital. DESIGN: A retrospective survey was made over two months as a clinical audit to assess professional practices. The evaluation criteria for this audit were: the appropriateness of the indication, the possibility of alternative therapeutic strategies, the choice of an antibiotic combination, duration of treatment and dosage. RESULTS: During the audit period, 103 carbapenem prescriptions were included. Ninety-nine cases were analyzed. Among the carbapenem prescriptions, 28.3% (28/99) did not meet the criterion "appropriateness of the indication". Carbapenems were mostly prescribed empirically (60/99 [60%]) and most often for lung infections or nosocomial urinary tract infections. Finally, 66.7% (66/99) of all prescriptions were considered inappropriate for at least one criterion. The rate of inappropriateness ranged around 30% for each criterion. CONCLUSIONS: This study allowed us to assess professional practices for carbapenem prescriptions. The overall rate of inappropriateness was quite important. Carbapenems were not always used appropriately. These findings highlight the need of new regional guidelines and regular updating of local best practices recommendations. Finally, a stricter validation of carbapenem prescriptions will be implemented at the hospital pharmacy level.

[Antibiotics in elderly patients: Impact of clinical practice evaluation]. / Antibiothérapie chez le sujet âgé : impact d'une démarche d'évaluation des pratiques professionnelles.

OBJECTIVE: Improving the use of antimicrobial drugs is a national objective. To this end an evaluation of clinical practice was implemented on prescribed antibiotics in elderly patients, in the Besançon Teaching Hospital. DESIGN: In 2005, a clinical audit compared the adequacy of antibiotic prescriptions to national guidelines in 37 patients. An improvement plan was implemented, including the drafting of local guidelines (adapted national guidelines) "Antibiotic prescription in elderly patients" by a multidisciplinary team. The Antibiotics Committee approved it. A retrospective study compared antibiotic prescription of 62 patients to these guidelines. The methodology was based on Gyssen's algorithm. The assessment criteria were: relevance of the indication, absence of a better alternative, respect of recommended dose, duration, and timing. RESULTS: The rate of overall conformity was 26% in 2005, 57% in 2007. Antibiotic choice was adequate in 61% of cases in 2005, 78% in 2007. In 63% of cases, a more efficient alternative was advised in 2005, 10% of cases in 2007. Treatment duration, dose, and timing were adequate in 54 - 92 - 96% in 2005 respectively and 86 - 92 - 100% of cases in 2007. Ciprofloxacin was prescribed in first line for 42% of urinary infections in 2005, 0% in 2007. CONCLUSIONS: This approach improved antibiotic prescriptions because of better guideline observance by physicians. The main improvement concerned fluoroquinolones. It should be continued to confirm antibiotic good use and protect our hospital bacterial ecology.

[Regional audit on fluoroquinolones usage in the hospital and the community: are these antibiotics over-used?]. / Audit régional de l'usage des fluoroquinolones à l'hôpital et en ville : y a-t-il une surconsommation de ces antibiotiques ?

AIM OF THE STUDY: The ecological impact of an over-use or a mis-use of fluoroquinolones (FQs) appears of great importance according to published data. With the objective to set up a regional antibiotic stewardship program, we conducted a regional audit on FQs usage. MATERIAL AND METHODS: [corrected] Ninety general practionners and 15 health care facilities participated to this prospective study. Overall, 511 prescriptions were evaluated (276 from hospital physicians and 235 [46%] from general practionners). The compliance of FQs prescription with national recommendations and with a regional referential was assessed. This regional referential was established in order to preserve FQs. RESULTS: Only 14,3% of the prescriptions complied with the regional referential, even if the choice of FQs were in accordance with national recommendations in 56,8% of the prescriptions. Urinary tract infections (mostly non-complicated) were the most common indication for FQs prescription. CONCLUSION: Analysis of FQs prescriptions shows that there is a significant potential for FQs preservation in Franche-Comté.

[Evaluation of antibiotic prescription in a French university hospital]. / Evaluation de la prescription antibiotique dans un centre hospitalier universitaire français.

OBJECTIVE: The aim of this study was to evaluate antibiotic prescription in a French university hospital. DESIGN: Our hospital participated in an international European Surveillance of Antimicrobial Consumption (ESAC) project study, including a longitudinal survey of monthly antibiotic use between 1998 and 2005, and a point prevalence study in 2006. All patients in the hospital on the day of survey were included in the study. Antibiotic treatments were assessed according to local antibiotic guidelines. RESULTS: Between 1998 and 2005, antibiotic use increased from 551.9 to 628.5 defined daily doses per 1000 patient-days. This increase was linked to the increase of penicillin and fluoroquinolone consumption. In the point prevalence survey, 251 (27.0%) of the 930 included patients received one or several antibiotics for a total of 395 antibiotic prescriptions. Community-acquired infections were the first indication of treatment (41.8% of prescriptions), hospital-acquired infections accounted for 34.9% of prescriptions, surgical and medical antibiotic prophylaxis for 22.4%. The assessment of antibiotic prescriptions showed that 73.7% of them were in conformity with local recommendations. CONCLUSIONS: This type of study is relevant to identify critical points of inadequate antibiotic use so as to suggest corrective measures to prescribers.

Are antibiotic-resistant Pseudomonas aeruginosa isolated from hospitalised patients recovered in the hospital effluents?

Previous reports have studied the presence of antibiotic-resistant Pseudomonas aeruginosa strains in hospital wastewater without determination of their clonal relationship with the clinical strains of this species. The objectives of this study were to quantify the presence of P. aeruginosa in wastewater of our hospital, to determine their antibiotic-resistance profile and to potentially trace clinical antibiotic-resistant strains from patients to wastewater. Specimens were taken at the end of the wastewater network of our hospital just before the reject in the collective network of the town. Two specimens were taken each Monday during 12 weeks. All P. aeruginosa isolates recovered from hospitalised patients during the study period were collected. Genotyping of both clinical and wastewater isolates was determined by using pulsed-field gel electrophoresis (PFGE). The antibiotic-resistance profile of wastewater isolates was different from that of clinical isolates. The mechanisms involved in antibiotic resistance were different according to the origin of the isolates (wastewater versus human isolates). There was no common PFGE pattern in antibiotic-resistant P. aeruginosa from humans and wastewater. This study suggests that the risk of spread of antibiotic resistance in hospital wastewater is limited.

Patient and bacterial determinants involved in symptomatic urinary tract infection caused by Escherichia coli with and without bacteraemia.

Risk-factors for bacteraemia were determined in a case-control study of patients with Escherichia coli urinary tract infection. Cases were defined as patients with E. coli urinary source bacteraemia, and controls were chosen from among patients with E. coli urinary tract infection without bacteraemia. Patient characteristics were collected prospectively and the bacterial traits were determined. The phylogenetic background and virulence factors of E. coli isolates did not differ between cases and controls. In multivariate analysis, being female and having a urinary catheter were significantly less prevalent among patients with urinary source bacteraemia than among patients with uncomplicated urinary tract infection.

[Surveillance of antimicrobial resistance and antimicrobial use in a university-affiliated hospital: implementation of a computerized system]. / Mise en place d'un outil informatisé de surveillance de la résistance bactérienne et de la consommation antibiotique dans un centre hospitalier universitaire.

UNLABELLED: After half a century of antibiotic use, the increasing problem of the emergence and spread of antimicrobial-resistant pathogens has created a problem of public health. The causes of this problem are multifactorial, but the excessive and inappropriate use of antimicrobials is the principal cause. The current guidelines for the control of antimicrobial resistance in hospitals recommend the implementation of a surveillance system of antimicrobial use and antimicrobial resistance data. AIM OF THE STUDY: The objective of our project was to develop a computerised tool to survey the antibiotic consumption data and the antimicrobial resistance. MATERIALS AND METHODS: We have collected antimicrobial resistance data from the software of the bacteriology laboratory, antibiotic use data from the pharmacy and demographical data from the hospital's admission department. These data were integrated in a database server and available with a web application. Antimicrobial resistance data of 15 major microorganisms were extracted and expressed as a frequency with elimination of repeats by using time criteria (7, 14 or 28 days). Antibiotic use data were converted into defined daily doses (DDD) and expressed per 1000 patient-days. RESULTS: Data are available for consultation in the form of tables or graphs per unit, type of units (medicine, surgery, pediatrics, intensive care units) or in the whole hospital. The system allows the confrontation on the same graph of antimicrobial resistance and antibiotic use data. CONCLUSION: Our surveillance system constitutes a needed prerequisite to the implementation of a global strategy of antibiotic use improvement in our hospital.

[Low-level resistance to fluoroquinolones conferred by efflux overproduction in Pseudomonas aeruginosa: clinical significance and routine detection]. / Résistance de bas niveau aux fluoroquinolones par surexpression de l'efflux chez Pseudomonas aeruginosa: conséquences thérapeutiques et détection au laboratoire.

The aim of this study was (i) to assess the impact of stable overproduction of efflux systems MexAB-OprM and MexXY-OprM on the bacteriostatic activities of fluoroquinolones in clinical Pseudomonas aeruginosa strains and (ii) to find a convenient test for screening isolates with a low level resistance to fluoroquinolones. The minimal inhibitory concentrations (MICs) of ciprofloxacin and levofloxacin were determined for clinical isolates of P. aeruginosa overexpressing MexAB-OprM or MexXY-OprM. Efflux pumps derepression was associated with a modest two- to fourfold increase in resistance to the tested fluoroquinolones. Clinical significance of low level resistance conferred by the efflux mechanism was evaluated with a Monte Carlo simulation with various fluoroquinolone regimens. With this model, low levels of resistance to ciprofloxacin (MIC > or =0.25 mg/L) or levofloxacin (MIC > or =1 mg/L) such as those due to overproduced MexAB-OprM or MexXY-OprM were predicted to result in poor clinical outcomes. Altogether these data strongly suggest that when derepressed MexAB-OprM or MexXY-OprM provides P. aeruginosa with a resistance that may be sufficient to impair the efficacy of single therapy with highly potent fluoroquinolones such as ciprofloxacin and levofloxacin. Routine detection of clinical strains that displayed low-level resistance to fluoroquinolones with a Mueller Hinton agar containing 0.20 mg/L of ciprofloxacin will help clinician in his therapeutical choice.

Susceptibility of Escherichia coli to the amoxycillin-clavulanate combination: which recommendations should be used to provide relevant information to clinicians?

This study compared MIC distributions of amoxycillin-clavulanate obtained with NCCLS and French (Comite de l'Antibiogramme de la Societe Francaise de Microbiologie; CA-SFM) methodologies for Escherichia coli isolates from urine that were non-susceptible to amoxycillin-clavulanate by the disk diffusion method. With the NCCLS and CA-SFM methods, 74% and 13%, respectively, of these isolates were susceptible to amoxycillin-clavulanate. Therefore, the apparent relatively poor efficacy of amoxycillin-clavulanate against E. coli in French hospitals probably reflects a methodological difference rather than a localised resistance problem. This implies that amoxycillin-clavulanate could be used as an alternative to fluoroquinolones for treatment of E. coli urinary tract infections. Susceptibility tests for amoxycillin-clavulanate should be standardised worldwide.

[Two efflux systems expressed simultaneously in clinical Pseudomonas aeruginosa]. / Deux systèmes d'efflux exprimés simultanément chez des souches cliniques de Pseudomonas aeruginosa.

Active efflux systems MexAB-OprM and MexXY were found to be overexpressed simultaneously in 12 multiresistant clinical isolates of Pseudomonas aeruginosa. Nine of these strains (agrZ mutants) harbored mutations in gene mexZ, the product of which down-regulates expression of operon mexXY. Eight of the 12 strains exhibited mutations in genes known to control transcription of operon mexAB-oprM, such as mexR (four nalB mutants) or PA3721 (three nalC mutants). One strain was a nalB/nalC double mutant. For MexAB-OprM as well as for MexXY, no clear correlation could be established between (i) the types of mutations, (ii) the over-expression levels of genes mexA or mexX, and (iii) the resistance levels to effluxed antibiotics. Finally, three and four isolates overproduced MexXY (agrW mutants) or MexAB-OprM (nalD mutants), respectively, without any mutation in the known regulator genes. These data show that clinical isolates are able to broaden their drug resistance profiles by coexpressing two Mex efflux pumps and suggest the existence of additional regulators for MexAB-OprM and MexXY.