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ABSTRACTThe risk of acquisition of multidrug-resistant Enterobacteriaceae (MRE) and of occurrence of diarrhea is high when traveling to tropical regions. The relationships between these phenomena and the composition of human gut microbiota have not yet been assessed. Here, we investigated the dynamics of changes of metabolically active microbiota by sequencing total RNA from fecal samples taken before and after travel to tropical regions. We included 43 subjects who could provide fecal samples before and after a travel to tropical regions. When found positive by culturing for any MRE after travel, the subjects sent an additional sample 1 month later. In all, 104 fecal samples were considered (43 before travel, 43 at return, 18 one month after travel). We extracted the whole RNA, performed retrotranscription and sequenced the cDNA (MiSeq 2x300bp). The reads were mapped to the reference operational taxonomic units (OTUs) and species/strains using the 16S Greengenes and 23S SILVA databases. We found that the occurrence of diarrhea during the travel was associated with a higher relative abundance of Prevotella copribefore departure and after return. The composition of microbiota, before travel as well as at return, was not correlated with the acquisition of MRE. However, the clearance of MRE one month after return was linked to a specific pattern of bacterial species that was also found before and after return. In conclusion, we found specific OTUs associated to a higher risk of diarrhea during a stay in tropical regions and to a faster clearance of MRE after their acquisition.

BACKGROUNDThe best strategy for controlling extended-spectrum β-lactamase-producing Enterobacteriaceae(ESBL-PE) transmission in intensive care units (ICUs) remains elusive.OBJECTIVEWe developed a stochastic transmission model to quantify the effectiveness of interventions aimed at reducing the spread of ESBL-PE in an ICU.METHODSWe modeled the evolution of an outbreak caused by the admission of a single carrier in a 10-bed ICU free of ESBL-PE. Using data obtained from recent muticenter studies, we studied 26 strategies combining different levels of the following 3 interventions: (1) increasing healthcare worker compliance with hand hygiene before and after contact with a patient; (2) cohorting; (3) reducing antibiotic prevalence at admission with or without reducing antibiotherapy duration.RESULTSImproving hand hygiene compliance from 55% before patient contact and 60% after patient contact to 80% before and 80% after patient contact reduced the nosocomial incidence rate of ESBL-PE colonization by 91% at 90 days. Adding cohorting to hand hygiene improvement intervention decreased the proportion of ESBL-PE acquisitions by an additional 7%. Antibiotic restriction had the lowest impact on the epidemic. When combined with other interventions, it only marginally improved effectiveness, despite strong hypotheses regarding antibiotic impact on transmission.CONCLUSIONOur results suggest that hand hygiene is the most effective intervention to control ESBL-PE transmission in an ICU.Infect. Control Hosp. Epidemiol.2016;37(3):272–280

ABSTRACTEpidemiological and individual risk factors for colonization by enterobacteria producing extended-spectrum beta-lactamases (E-ESBL) have been studied extensively, but whether such colonization is associated with significant changes in the composition of the rest of the microbiota is still unknown. To address this issue, we assessed in an isolated Amerindian Guianese community whether intestinal carriage of E-ESBL was associated with specificities in gut microbiota using metagenomic and metatranscriptomic approaches. While the richness of taxa of the active microbiota of carriers was similar to that of noncarriers, the taxa were less homogeneous. In addition, species of four genera, Desulfovibrio,Oscillospira, Parabacteroides, and Coprococcus, were significantly more abundant in the active microbiota of noncarriers than in the active microbiota of carriers, whereas such was the case only for species of Desulfovibrioand Oscillospirain the total microbiota. Differential genera in noncarrier microbiota could either be associated with resistance to colonization or be the consequence of the colonization by E-ESBL.

ABSTRACTExtended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli(ESBL E. coli) strains are of major concern because few antibiotics remain active against these bacteria. We investigated the association between the fecal relative abundance (RA) of ESBL-producing E. coli(ESBL-RA) and the occurrence of ESBL E. coliurinary tract infections (UTIs). The first stool samples passed after suspicion of UTI from 310 women with subsequently confirmed E. coliUTIs were sampled and tested for ESBL-RA by culture on selective agar. Predictive values of ESBL-RA for ESBL E. coliUTI were analyzed for women who were not exposed to antibiotics when the stool was passed. ESBL E. coliisolates were characterized for ESBL type, phylogroup, relatedness, and virulence factors. The prevalence of ESBL E. colifecal carriage was 20.3%, with ESBL E. coliUTIs being present in 12.3% of the women. The mean ESBL-RA (95% confidence interval [CI]) was 13-fold higher in women exposed to antibiotics at the time of sampling than in those not exposed (14.3% [range, 5.6% to 36.9%] versus 1.1% [range, 0.32% to 3.6%], respectively; P< 0.001) and 18-fold higher in women with ESBL E. coliUTI than in those with another E. coliUTI (10.0% [range, 0.54% to 100%] versus 0.56% [range, 0.15% to 2.1%[, respectively; P< 0.05). An ESBL-RA of <0.1% was 100% predictive of a non-ESBL E. coliUTI. ESBL type, phylogroup, relatedness, and virulence factors were not found to be associated with ESBL-RA. In conclusion, ESBL-RA was linked to the occurrence of ESBL E. coliUTI in women who were not exposed to antibiotics and who had the same clone of E. coliin urine samples and fecal samples. Especially, a low ESBL-RA appeared to be associated with a low risk of ESBL E. coliinfection.

ABSTRACTIntestinal flora contains a reservoir of Gram-negative bacilli (GNB) resistant to cephalosporins, which are potentially pathogenic for intensive care unit (ICU) patients; this has led to increasing use of carbapenems. The emergence of carbapenem resistance is a major concern for ICUs. Therefore, in this study, we aimed to assess the intestinal carriage of imipenem-resistant GNB (IR-GNB) in intensive care patients. For 6 months, 523 consecutive ICU patients were screened for rectal IR-GNB colonization upon admission and weekly thereafter. The phenotypes and genotypes of all isolates were determined, and a case control study was performed to identify risk factors for colonization. The IR-GNB colonization rate increased regularly from 5.6% after 1 week to 58.6% after 6 weeks in the ICU. In all, 56 IR-GNB strains were collected from 50 patients: 36 Pseudomonas aeruginosastrains, 12 Stenotrophomonas maltophiliastrains, 6 Enterobacteriaceaestrains, and 2 Acinetobacter baumanniistrains. In P. aeruginosa, imipenem resistance was due to chromosomally encoded resistance (32 strains) or carbapenemase production (4 strains). In the Enterobacteriaceaestrains, resistance was due to AmpC cephalosporinase and/or extended-spectrum β-lactamase production with porin loss. Genomic comparison showed that the strains were highly diverse, with 8 exceptions (4 VIM-2 carbapenemase-producing P. aeruginosastrains, 2 Klebsiella pneumoniaestrains, and 2 S. maltophiliastrains). The main risk factor for IR-GNB colonization was prior imipenem exposure. The odds ratio for colonization was already as high as 5.9 (95% confidence interval [95% CI], 1.5 to 25.7) after 1 to 3 days of exposure and increased to 7.8 (95% CI, 2.4 to 29.8) thereafter. In conclusion, even brief exposure to imipenem is a major risk factor for IR-GNB carriage.

ABSTRACTWe investigated the efficiency of the cephamycin cefoxitin as an alternative to carbapenems for the treatment of urinary tract infections (UTIs) due to Escherichia coliproducing CTX-M-type extended-spectrum β-lactamases. The susceptible, UTI-inducing E. coliCFT073-RR strain and its transconjugant CFT073-RR Tc (pblaCTX-M-15), harboring a blaCTX-M-15carrying-plasmid, were used for all experiments. MICs of cefoxitin (FOX), ceftriaxone (CRO), imipenem (IMP), and ertapenem (ETP) for CFT073-RR and CFT073-RR Tc (pblaCTX-M-15) were 4 and 4, 0.125 and 512, 0.5 and 0.5, and 0.016 and 0.032 μg/ml, respectively. Bactericidal activity was similarly achieved in vitroagainst the two strains after 3 h of exposure to concentrations of FOX, IMI, and ETP that were 2 times the MIC, whereas CRO was not bactericidal against CFT073-RR Tc (pblaCTX-M-15). The frequencies of spontaneous mutants of the 2 strains were not higher for FOX than for IMP or ETP. In the murine model of UTIs, mice infected for 5 days were treated over 24 h. Therapeutic regimens in mice (200 mg/kg of body weight every 3 h or 4 h for FOX, 70 mg/kg every 6 h for CRO, 100 mg/kg every 2 h for IMP, and 100 mg/kg every 4 h for ETP) were chosen in order to reproduce the percentage of time that free-drug concentrations above the MIC are obtained in humans with standard regimens. All antibiotic regimens produced a significant reduction in bacterial counts (greater than 2 log10CFU) in kidneys and bladders for both strains (P< 0.001) without selecting resistant mutants in vivo, but the reduction obtained with CRO against CFT073-RR Tc (pblaCTX-M-15) in kidneys was significantly lower than that obtained with FOX. In conclusion, FOX appears to be an effective therapeutic alternative to carbapenems for the treatment of UTIs due to CTX-M-producing E. coli.

ABSTRACTNasal carriage of methicillin-resistant coagulase-negative staphylococci (MR-CoNS) is highly prevalent in community subjects, but its dynamic has been little investigated. Nasal swabbing was performed in 2006 and 2008 in 154 Amerindians living isolated in French Guiana. MR-CoNS strains were identified and characterized by non-β-lactam susceptibility testing and staphylococcal cassette chromosome mecelement (SCCmec) typing, characterizing the associations of ccrand mecgene complex allotypes, and for MR Staphylococcus epidermidis(MRSE), multilocus variable number of tandem repeats analysis (MLVA) was used. The impact of sociodemographic and medical characteristics on the persistence of MR-CoNS carriage was assessed by bivariate analysis. Prevalence of MR-CoNS carriage was 50.6% in 2006 and 46.8% in 2008. The 274 MR-CoNS isolates, including S. epidermidis(n= 89, 62 MLVA patterns), Staphylococcus haemolyticus(n= 78), and Staphylococcus hominis(n= 72), exhibited 41 distinct ccrand mecgene complex associations. Persistent carriage (in 2006 and 2008), intermittent carriage (either in 2006 or 2008), and noncarriage were documented in 25.3, 47.4, and 27.3% of the participants, respectively. Persistent carriage of a given MRSE isolate was rarely observed (n= 8 isolates). Furthermore, no epidemiological factor, including antibiotic exposure, was associated with persistent carriage. The high diversity of MRSE clones and their ccrand mecgene complex associations contrasted with the high carriage rates in this isolated community, which might reflect the occurrence of SCCmecrearrangement and the generation of new MR-CoNS strains.

ABSTRACTThe important role of commensal flora as a natural reservoir of bacterial resistance is now well established. However, whether the behavior of each commensal flora is similar to that of other floras in terms of rates of carriage and risk factors for bacterial resistance is unknown. During a 6-month period, we prospectively investigated colonization with fluoroquinolone-resistant bacteria in the three main commensal floras from hospitalized patients at admission, targeting Escherichia coliin the fecal flora, coagulase-negative Staphylococcus(CNS) in the nasal flora, and α-hemolytic streptococci in the pharyngeal flora. Resistant strains were detected on quinolone-containing selective agar. Clinical and epidemiological data were collected. A total of 555 patients were included. Carriage rates of resistance were 8.0% in E. coli, 30.3% in CNS for ciprofloxacin, and 27.2% in streptococci for levofloxacin; 56% of the patients carried resistance in at least one flora but only 0.9% simultaneously in all floras, which is no more than random. Risk factors associated with the carriage of fluoroquinolone-resistant strains differed between fecal E. coli(i.e., colonization by multidrug-resistant bacteria) and nasal CNS (i.e., age, coming from a health care facility, and previous antibiotic treatment with a fluoroquinolone) while no risk factors were identified for pharyngeal streptococci. Despite high rates of colonization with fluoroquinolone-resistant bacteria, each commensal flora behaved independently since simultaneous carriage of resistance in the three distinct floras was uncommon, and risk factors differed. Consequences of environmental selective pressures vary in each commensal flora according to its local specificities (clinical trial NCT00520715 [http://clinicaltrials.gov/ct2/show/NCT00520715]).

ABSTRACTIn staphylococci, methicillin (meticillin) resistance (MR) is mediated by the acquisition of the mecAgene, which is carried on the size and composition variable staphylococcal cassette chromosome mec(SCCmec). MR has been extensively studied in Staphylococcus aureus, but little is known about MR coagulase-negative staphylococci (MR-CoNS). Here, we describe the diversity of SCCmecstructures in MR-CoNS from outpatients living in countries with contrasting environments: Algeria, Mali, Moldova, and Cambodia. Their MR-CoNS nasal carriage rates were 29, 17, 11, and 31%, respectively. Ninety-six MR-CoNS strains, comprising 75 (78%) Staphylococcus epidermidisstrains, 19 (20%) Staphylococcus haemolyticusstrains, 1 (1%) Staphylococcus hominisstrain, and 1 (1%) Staphylococcus cohniistrain, were analyzed. Eighteen different SCCmectypes were observed, with 28 identified as type IV (29%), 25 as type V (26%), and 1 as type III (1%). Fifteen strains (44%) were untypeable for their SCCmec. Thirty-four percent of MR-CoNS strains contained multiple ccrcopies. Type IV and V SCCmecwere preferentially associated with S. epidermidisand S. haemolyticus, respectively. MR-CoNS constitute a widespread and highly diversified MR reservoir in the community.

ABSTRACTTwo out of 20 children with no known antibiotic exposure, living in a very remote Senegalese village, were found to be fecal carriers of a multiresistant Escherichia coliclone that produced CTX-M-15. This highlights the current massive spread of extended-spectrum β-lactamases, even in isolated communities.

ABSTRACTWe report incidental isolation of an OXA-48-producing Escherichia colistrain in urine of a 62-year-old woman recently returning from a 2-month vacation in Morocco. Commercially available extended-spectrum beta-lactamase (ESBL)-targeting medium failed to detect it in the patient's stools, although a locally developed and easy-to-implement method using ertapenem-supplemented brain heart infusion (BHI) broths could.