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.

Demonstration of the herd effect in adults after the implementation of pneumococcal vaccination with PCV13 in children.

The purpose of this investigation was to describe the evolution of serotypes and antibiotic susceptibility of Streptococcus pneumoniae strains isolated from both adults and children from the same population area with invasive pneumococcal disease (IPD) or acute otitis media (AOM), 5 years after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). From 2009 to 2015, 839 strains of S. pneumoniae strains were collected (481 from adults and 358 from children). Serotyping by latex antisera and molecular methods was performed. Antimicrobial susceptibility was tested. Compared to 2009, the total number of strains isolated in 2015 decreased in children (263 vs. 53, respectively) and in adults (220 vs. 131, respectively). Serotype coverage of PCV13 for IPD decreased significantly in adults from 67.7% (149/220) to 25.2% (33/131) and in children from 75.1% (61/81) to 18.5% (5/27). Especially, serotypes 1, 7F and 19A decreased significantly in children, while serotypes 7F and 19A decreased significantly in adults. PCV13 serotypes involved in AOM decreased significantly over the 5-year period, from 85.7% (156/182) to 38.5% (10/26), and were more susceptible to penicillin, amoxicillin and cefotaxime, p < 0.05. Serotypes 8, 9N and 10A seemed to emerge in adults, whereas any serotype prevalence was observed in children. Between 2009 and 2015, the introduction of PCV13 has resulted in a significant decrease of the number of S. pneumoniae strains isolated from IPD in children as in adults. It highlights a strong herd effect of vaccination in adults.

Evidence of a clonal expansion of Streptococcus pneumoniae serotype 19A in adults as in children assessed by the DiversiLab® system.

Streptococcus pneumoniae serotype 19A was the main serotype responsible for invasive pneumococcal disease (IPD) in the Paris area in 2007 and 2009 in both adults and children. To verify if a particular clone is emerging, we determined the populational structure of S. pneumoniae isolates. Eighty-four S. pneumoniae strains responsible for invasive infections isolated from 52 adults and 32 children hospitalized in Parisian hospitals were analyzed. Capsular typing was performed by polymerase chain reaction (PCR) using the semi-automated repetitive sequence-based (rep-PCR) DiversiLab® System. Multilocus sequence typing (MLST) was also performed on 26 strains (ten selected strains after cluster analysis and 16 control strains). In 2007 and 2009, S. pneumoniae serotype 19A represented, respectively, 28.6 % and 25 % of the serotypes involved in IPDs in children and 13 % and 13.7 % in adults. The rep-PCR DiversiLab® analysis showed that the 84 S. pneumoniae serotype 19A isolates were distributed in five clusters and four unique rep-PCR types. Overall, 77/84 (91.6 %) S. pneumoniae 19A serotypes grouped into three main genetically related clusters (71/77 belonged to the cluster I). The five other strains exhibited different profiles. Using MLST, we demonstrated that most strains of the main cluster belonged to clonal complex (CC) 230, sequence type (ST) 276. However, for the other strains, the DiversiLab® method cannot be used to predict to which ST a strain belongs. The DiversiLab® method allowed us to identify the clonal expansion of S. pneumoniae serotype 19A strains isolated from both children and adults in 2007 and 2009.

Epidemiology of Streptococcus pneumoniae in France before introduction of the PCV-13 vaccine.

The purpose of this article was to describe the serotype incidence and antibiotic susceptibility of Streptococcus pneumoniae strains isolated from adults and children with invasive disease (IPD) or acute otitis media (AOM) before introduction of the 13-valent pneumococcal vaccine. During 2009, 494 strains of S. pneumoniae isolated were collected. Complete serotyping by latex antisera and molecular methods was performed. The most frequent serotypes isolated from children with IPD were 1 (26.2%), 19A (25%) and 7F (14.3%). Serotype 19A was predominant (42.1%) in children ≤ 2 years, whereas serotype 1 was predominant (63.3%) after the age of 5. Serotype 19A was the most frequently isolated serotype from AOM (62.3%). In adults, serotypes responsible for IPD were 7F (19.4%), 19A (13.7%), 1 (8.4%) and 3 (7.5%). The serotype 19A was predominant in adults older than 65 years (19.1%). The emergence of serotype 12F was observed in adults. Between 2007 and 2009, the introduction of PCV-7 has resulted in a significant decrease of IPD caused by serotypes included in the vaccine, in children as well as in adults, confirming the herd effect. Serotype coverage of PCV-13 was 70% and 80.9% for adult and children's IPD, respectively. PCV-13 will be more efficient in preventing invasive diseases among children and adults.

Benefits of a 14-year surgical site infections active surveillance programme in a French teaching hospital.

BACKGROUND: Surgical site infections (SSIs) are the second most common healthcare-associated infection. Active SSI surveillance can help inform preventative measures and assess the impact of these measures. AIM: We aimed to describe the evolution in trends over 14 years of prospective active SSI surveillance and implementations of SSI prevention measures in a French Teaching Hospital. METHODS: We monitored and included in the study all surgical procedures performed from 2003 to 2016 in eight surgical units. The semi-automated surveillance method consisted of weekly collection of SSI declaration forms (pre-filled with patient and procedure administrative data and microbiology laboratory data), filled-in by surgeons and then monitored by the infection control practitioners. FINDINGS: A total of 181,746 procedures were included in our analysis and 3270 SSIs recorded (global SSI rate 1.8%). The SSI rate decreased significantly from 3.0% in 2003 to 1.1% in 2016. This decrease was mainly in superficial SSIs and high infectious risk procedures. Higher SSI rates were observed for procedures associated with the usual risk factors. During this 14-year period, several evolutions in surgical practices occurred that might have contributed to this decrease. CONCLUSIONS: With an overall decrease in SSI rate throughout the surveillance, our results revealed the benefits of an active and comprehensive hospital SSI surveillance programme for understanding the SSI rate trends, analysing local risk factors and assessing the effectiveness of prevention strategies. These findings also highlighted the importance of the collaboration between surgeons and infection control practitioners.

Quantitative multiplex real-time PCR for detecting class 1, 2 and 3 integrons.

OBJECTIVES: Integrons are bacterial genetic elements that can capture and express genes contained in mobile cassettes. Integrons have been described worldwide in Gram-negative bacteria and are a marker of antibiotic resistance. We developed a specific and sensitive Taqman probe-based real-time PCR method with three different primer-probe pairs for simultaneous detection of the three main classes of integron. METHODS: Sensitivity was assessed by testing mixtures of the three targets (intI integrase genes of each integron class) ranging from 10 to 10(8) copies. Specificity was determined with a panel of integron-containing and integron-free control strains. The method was then applied to clinical samples. RESULTS: The PCR method was specific and had a sensitivity of 10(2) copies for all three genes, regardless of their respective quantities. The method was quantitative from 10(3) to 10(7) copies, and was able to detect integrons directly in biological samples. CONCLUSIONS: We have developed a rapid, quantitative, specific and sensitive method that could prove useful for initial screening of Gram-negative isolates, or clinical samples, for likely multidrug resistance.

Community-acquired bacterial meningitis in adults: in-hospital prognosis, long-term disability and determinants of outcome in a multicentre prospective cohort.

OBJECTIVES: To identify factors associated with unfavourable in-hospital outcome (death or disability) in adults with community-acquired bacterial meningitis (CABM). METHODS: In a prospective multicentre cohort study (COMBAT; February 2013 to July 2015), all consecutive cases of CABM in the 69 participating centres in France were enrolled and followed up for 12 months. Factors associated with unfavourable outcome were identified by logistic regression and long-term disability was analysed. RESULTS: Among the 533 individuals enrolled, (Streptococcus pneumoniae 53.8% (280/520 isolates identified), Neisseria meningitidis 21.3% (111/520), others 24.9% (129/520)), case fatality rate was 16.9% (90/533) and unfavourable outcome occurred in 45.0% (225/500). Factors independently associated with unfavourable outcome were: age >70 years (adjusted odds ratio (aOR) 4.64; 95% CI 1.93-11.15), male gender (aOR 2.11; 95% CI 1.25-3.57), chronic renal failure (aOR 6.65; 95% CI 1.57-28.12), purpura fulminans (aOR 4.37; 95% CI 1.38-13.81), localized neurological signs (aOR 3.72; 95% CI 2.29-6.05), disseminated intravascular coagulation (aOR 3.19; 95% CI 1.16-8.79), cerebrospinal fluid (CSF) white-cell count <1500 cells/µL (aOR 2.40; 95% CI 1.42-4.03), CSF glucose concentration (0.1-2.5 g/L: aOR 1.92; 95% CI 1.01-3.67; <0.1 g/L: aOR 2.24; 95% CI 1.01-4.97), elevated CSF protein concentration (aOR 1.09; 95% CI 1.03-1.17), time interval between hospitalization and lumbar puncture >1 day (aOR 2.94; 95% CI 1.32-6.54), and S. pneumoniae meningitis (aOR 4.99; 95% CI 1.98-12.56), or meningitis other than N. meningitidis (aOR 4.54; 95% CI 1.68-12.27). At 12 months, 26.7% (74/277) had hearing loss, 32.8% (87/265) depressive symptoms, 31.0% (86/277) persistent headache, and 53.4% had a physical health-related quality of life (142/266) <25th centile of the distribution of the score in the general French population (p < 0.0001). CONCLUSIONS: The burden of CABM (death, disability, depression, impaired quality of life and hearing loss) is high. Identification of cases from the first symptoms may improve prognosis. CLINICALTRIAL: Gov identification number: NCT01730690.

[Research and development strategies, examples among new vaccines]. / Stratégies de recherche et développement, illustrées par les nouveaux vaccins.

Classical methods are still providing new vaccines, but molecular biology and genetic engineering have enabled new approaches to development. Changes in vaccinology have involved the isolation, presentation and administration of vaccinal antigens or attenuated vaccinal strains. New methods of vaccine delivery other than injection will be used (e.g. mucosal administration) and new vectors or adjuvants will be added to vaccines in order to stimulate specific responses. New vaccines can also be obtained by using viral-like particles (VLP of papillomavirus), conjugate polysaccharides (N. meningitidis, S. pneumoniae) or the reassortment of segmented genomes (rotavirus, influenza). Here, we analyze the different steps of a vaccine's life using concrete cases of two new vaccines against papillomavirus and rotavirus. Vaccination has a promising future.

Role of superantigenic strains in the prognosis of community-acquired methicillin-susceptible Staphylococcus aureus bacteraemia.

Methicillin-susceptible Staphylococcus aureus (MSSA) strains can produce superantigenic toxins that may trigger a massive release of pro-inflammatory cytokines, which are involved in the onset of septic shock. This 1-year prospective pilot study assessed the role of the production of superantigenic toxins in the outcome of immunocompetent patients hospitalised for community-acquired MSSA bacteraemia. Thirty-seven patients were enrolled, of whom 14 died in hospital. Fourteen patients had septic shock, and the mortality rate in this subgroup was 56%. Twenty-seven (73%) isolates produced at least one superantigenic toxin, but this did not influence the rate of occurrence of septic shock or death.

Staphylococcus Aureus Carriage in French Athletes at Risk of CA-MRSA Infection: a Prospective, Cross-sectional Study.

BACKGROUND: Staphylococcus aureus (SA) is a leading cause of infectious diseases in sports teams. In recent decades, community-associated SA (CA-SA) strains have emerged worldwide and have been responsible for outbreaks in sports teams. There are very few data on the prevalence of these strains in France, and none on the carriage among athletes. METHODS: We conducted a cross-sectional study to determine the SA carriage proportion among athletes practicing sports at risk for CA-SA infection in a French county, and determined the methicillin-resistant and/or CA-SA proportion. We also analyzed SA carriage according to risks factors and studied the SA clonality in a sample of our population. RESULTS: We included 300 athletes; SA carriage proportion was 61% (n = 183) and one was MRSA carrier (0.33%). The MRSA strain belonged to the clonal complex ST5. None of the strain produced Panton Valentine Leucocidin, and we did not find clonal distribution within the teams. Interestingly, we found a high throat-only carriage (n = 57), 31.1% of the SA carriers. CONCLUSION: We found a high SA carriage with a local epidemiology quite different than that reported in a similar population in the USA. Further studies on SA carriage should include throat sampling. TRIAL REGISTRATION: The approved protocol was registered on ClinicalTrial.gov , NCT01148485.

Occurrence of qnrA-positive clinical isolates in French teaching hospitals during 2002-2005.

Bacteria harbouring the novel qnrA plasmid-mediated mechanism of quinolone resistance have been described in different countries, but the frequency of their occurrence has not been investigated. In total, 1,468 clinical isolates of Enterobacteriaceae with quinolone resistance or extended-spectrum beta-lactamase (ESBL) phenotypes were collected from eight teaching hospitals in France during 2002-2005 and screened for qnrA. Overall, 28 isolates (22 Enterobacter cloacae, three Klebsiella pneumoniae, one Citrobacter freundii, one Klebsiella oxytoca and one Proteus mirabilis) were positive for qnrA, representing 1.9% of all isolates, 3.3% of ESBL-producing isolates (22% of the E. cloacae isolates) and 0% of non-ESBL-producing isolates. The prevalence of qnrA among consecutive ESBL-producing isolates in 2004 from the eight hospitals was 2.8% (18/639). Of the qnrA-positive isolates, 100% were intermediately-resistant or resistant to nalidixic acid, and 75% to ciprofloxacin. Twenty-one of the 22 qnrA-positive E. cloacae isolates were obtained from two hospitals in the Paris area, and molecular typing and plasmid content analysis showed clonal relationships for five, three and two isolates, respectively. The qnrA genetic environment was similar to that of the In36 integron. The remaining two isolates had qnrA variants (30 and 29 nucleotide differences, respectively, compared with the original sequence) and an unknown genetic environment. The ESBL gene associated with qnrA was bla(SHV-12) in most of the isolates, but bla(PER-1) and bla(SHV-2a) were found in two isolates. In France, it appears that qnrA-positive isolates are predominantly E. cloacae isolates producing SHV-12, and may be associated with the dissemination of an In36-like integron.

Molecular quantification of bacteria from respiratory samples in patients with suspected ventilator-associated pneumonia.

Ventilator-associated pneumonia (VAP) is the most common infection in critically ill patients. Initial antibiotic therapy is often broad spectrum, which promotes antibiotic resistance so new techniques are under investigation to obtain early microbiological identification and quantification. This trial compares the performance of a new real-time quantitative molecular-based method with conventional culture in patients with suspected VAP. Patients with suspected VAP who were ventilated for at least 48 h were eligible. An endotracheal aspirate (ETA) and a bronchoalveolar lavage (BAL) were performed at each suspected VAP episode. Both samples were analysed by conventional culture and molecular analysis. For the latter, bacterial DNA was extracted from each sample and real-time PCR were run. In all, 120 patients were finally included; 76% (91) were men; median age was 65 years, and clinical pulmonary infection score was ≥6 for 73.5% (86) of patients. A total of 120 BAL and 103 ETA could be processed and culture results above the agreed threshold were obtained for 75.0% (90/120) of BAL and 60.2% (62/103) of ETA. The main isolated bacteria were Staphylococcus aureus, Pseudomonas aeruginosa and Haemophilus influenzae. Performance was 89.2% (83.2%-93.6%) sensitivity and 97.1% (96.1%-97.9%) specificity for BAL samples and 71.8% (61.0%-81.0%) sensitivity and 96.6% (95.4%-97.5%) specificity for ETA samples when the molecular biology method was compared with conventional culture method (chosen as reference standard). This new molecular method can provide reliable quantitative microbiological data and is highly specific with good sensitivity for common pathogens involved in VAP.

In vitro activity of josamycin against Streptococcus pyogenes isolated from patients with upper respiratory tract infections in France.

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 MIC50 and MIC90 of josamycin against 193 isolates of S. pyogenes were 0.12 and 0.25mg/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.

Highly virulent M1 Streptococcus pyogenes isolates resistant to clindamycin.

CONTEXT: Emm1-type group A Streptococcus (GAS), or Streptococcus pyogenes, is mostly responsible for invasive infections such as necrotizing fasciitis (NF) and streptococcal toxic shock syndrome (STSS). The recommended treatment of severe invasive GAS infections is a combination of clindamycin and penicillin. Until 2012, almost all emm1 isolates were susceptible to clindamycin. OBJECTIVES: We aimed to identify the phenotypic and genotypic characteristics of emm1 GAS clone resistant to clindamycin. METHODS: GAS strains were characterized by emm sequence typing, detection of genes encoding pyrogenic exotoxins or superantigens. Cluster analysis was performed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Antibiotic susceptibility was assessed using disk diffusion and resistance genes were detected by PCR. RESULTS: A total of 1321 GAS invasive isolates were analyzed between January 2011 and December 2012. The overall number of invasive isolates resistant to clindamycin was 52 (3.9%); seven of them were emm1 isolates. All isolates had the same genomic markers: macrolide resistance due to the presence of the erm(B) gene, emm subtype 1.0, the same toxin or superantigen profile, PFGE pattern and sequence type. CONCLUSION: This is the first description of highly virulent GAS emm1 isolates resistant to clindamycin in France. This article strengthens the need for monitoring the epidemiology of invasive GAS strains as they could lead to changes in treatment guidelines.

Ex vivo model of congenital cytomegalovirus infection and new combination therapies.

INTRODUCTION: Congenital human cytomegalovirus (HCMV) infection is a major public health problem due to severe sequelae in the fetus and newborns. Currently, due to their toxicity anti-CMV treatments cannot be administered to pregnant women. We thus developed an ex vivo model of 1(st) trimester placental CMV infection to observe the route of infection across the placenta and to test the efficacy of various new drugs targeting different stages of viral cycle. METHODS: After validation of the viability of floating villi explants by ELISA ß-HCG, the kinetics of placental infection were determined by immunochemistry and qPCR in this ex vivo model. Antiviral susceptibility was determined in vitro using focus reduction assay and by qPCR in the ex vivo model. RESULTS: The ex vivo model showed viral infection in trophoblasts and mesenchymal space of floating villi. In vitro, antiviral combinations of maribavir with baïcalein or artesunate inhibited viral infection by more than 90%. On the other hand, in ex vivo model, infection was reduced by 40% in presence of maribavir and artesunate. The synergistic effect observed in vitro was not observed ex vivo. DISCUSSION: This model allowed us to understand the CMV spread in 1(st) trimester floating villi better and to analyze the anti-CMV efficacy and toxicity of new drugs that could be administered to pregnant women, either alone or in combination. CONCLUSIONS: Such an ex vivo model could be applied to other viruses such as rubella or parvovirus B19 and in new drug development.

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.

A spontaneous point mutation in the aac(6')-Ib' gene results in altered substrate specificity of aminoglycoside 6'-N-acetyltransferase of a Pseudomonas fluorescens strain.

The aac(6')-Ib' gene from Pseudomonas fluorescens BM2687, encoding an aminoglycoside 6'-N-acetyltransferase type II which confers resistance to gentamicin but not to amikacin, was characterized. Nucleotide sequence determination indicated total identity between aac(6')-Ib' and the aac(6')-Ib gene from Pseudomonas aeruginosa BM2656 [1] with the exception of a C-to-T transition that results in a serine to leucine substitution at position 83 of the deduced polypeptide. The aac(6')-Ib gene specifies a type I enzyme which confers resistance to amikacin but not to gentamicin [2]. It thus appears that the point mutation detected is responsible for enzymic altered substrate specificity.

Use of antibiotics in hospitals in south-western France.

Data on the use of antibiotics were collected by means of a questionnaire from 49 hospitals in south-western France. Use was expressed as a usage density rate: number of defined daily doses (DDDs) per 1000 patient-days. The average use of antibiotics amounted to 402 DDDs per 1000 patient-days and varied between 60 and 734. In acute-care wards, the amount of antibiotic use increased with the size of the hospital: 461 DDDs per 1000 patient-days for group A (<100 beds), 510 DDDs per 1000 patient-days for group B (more than 100 and less then 300 beds) and 676 DDDs per 1000 patient-days for group C (>300 beds). The rate of use differed among different types of hospital areas and varied from 58 for psychiatry departments to more than 1273 DDDs per 1000 patient-days for the infectious diseases departments. Broad-spectrum penicillins were the most frequently prescribed antibiotics. Fluoroquinolone and third-generation cephalosporin use were relatively uniform in the three size categories. This study shows that it is possible for a hospital to benchmark its consumption with other hospitals that are similar in size. In this way, surveillance of antibiotic use can aid hospitals in targeting infection control efforts.

[The role of integrons in dissemination of antibiotic resistance]. / Place des intégrons dans la dissémination de la résistance aux antibiotiques.

Bacteria can transfer genetic information to get protection against most antibiotics. The acquisition of resistance genes involves genetic mobile elements such as plasmids and transposons. Another genetic structures, named integrons, have been described and contain one or more gene cassettes located at a specific site. Integrons contain an intI gene encoding a site-specific recombinase belonging to the integrase family and a recombination site attI. A gene cassette includes an open reading frame and, at the 3'-end, a recombination site attC. Integration or excision of cassettes occurs by a site-specific recombination mechanism catalyzed by the integrase. However, insertion can rarely occur, at non-specific sites leading to a stable situation for the cassette. Cassettes are transcribed from a common promoter located in the 5'-conserved segment and expression of distal genes is reduced by the presence of upstream cassettes. Most gene cassettes encode antibiotic resistant determinants but antiseptic resistant genes have also been described. Integrons seem to have a major role in the spread of multidrug resistance in Gram-negative bacteria but integrons in Gram-positive bacteria have been recently described. Moreover, the finding of super-integrons with gene cassettes coding for other determinants (biochemical functions, virulence factors) in different Gram negative bacteria suggests that integrons are probably implied in bacterial genome evolution.