Acquisition and transmission of ESBL producing ent erobacteriaceae among community subjects in highly endemic areas

Le portage et les infections à entérobactéries productrices de bêta-lactamase à spectre étendu (E-BLSE) touchent de plus en plus fréquemment les sujets communautaires. La prévalence de portage dans la communauté a été estimée à 30 et 70% respectivement en Afrique et en Asie alors qu’elle n’est que de 10% en Europe. Le fait de vivre ou de séjourner dans des zones de forte endémie constitue donc un facteur de risque élevé d’acquisition d’E-BLSE. La prévalence du portage d’entérobactéries résistantes dans les zones intertropicales et les facteurs de risque d’acquisition par un sujet individuel lors de l’exposition à de tels environnements ont été largement étudiés mais la question des transmissions secondaires à partir de ces cas index n’a pas été appréhendée alors qu’elle est essentielle, notamment pour comprendre son impact dans la diffusion des E-BLSE dans la communauté. Nous avons étudié l’acquisition et la transmission des E-BLSE au sein de deux cohortes de sujets vivant en zones de forte endémie et en promiscuité avec d’autres individus au moment de l’acquisition. Nous avons utilisé dans ce but des techniques de PCR et de séquençage de génome complet (WGS) associé à une fine analyse des single nucleotide polymorphisms (SNPs). La première cohorte était constituée de militaires en mission dans 3 régions différentes, l’Afghanistan, la Guyane et la Côte d’Ivoire. Les taux d'acquisition d'E-BLSE pendant la mission étaient variables selon les destinations : 88% en Afghanistan, 49% en Côte d’Ivoire et 5% en Guyane. La transmission d’E. coli BLSE entre les militaires, étudiée au sein de la compagnie afghane, n’a permis de mettre en évidence aucune transmission de souches dans cette compagnie. Les bonnes conditions d’hygiène dans le campement et le peu de contact avec la population locale suggéreraient que le fort taux d’acquisition observé pourrait être dû à une acquisition individuelle, à partir de repas achetés régulièrement auprès des nombreux vendeurs ambulants installés autour du campement. La deuxième cohorte était issue d’une étude contre placebo réalisée chez des enfants dénutris non hospitalisés vivant au Niger. Ce travail avait pour objectif de mesurer l’impact de l’amoxicilline administrée de façon systématique dans les protocoles de renutrition des enfants présentant une malnutrition sévère, sur la colonisation par des E-BLSE et sur la transmission des souches au sein desfratries. Nous avons observé que l’administration d’amoxicilline augmentait le risque d’acquisition d’E-BLSE chez l’enfant traité dans la semaine qui suivait sa prise en charge (54% vs 32%, p<0,001) ainsi que le risque de transmission d’une E-BLSE dans la fratrie (11.5% vs 3.8%, p=0.04). Au total, dans ces deux études nous avons pu montrer que la caractérisation complète des souches par WGS et l’analyse des SNPs apportait des informations incontournables pour comprendre la dynamique de partage des souches d’E-BLSE entre les sujets. Ces études apportent des éléments de réponses sur la transmission des E-BLSE dans la communauté et les facteurs de risques associés, mais d’autres facteurs de risques et d’autres situations restent encore à explorer avec ces nouveaux outils.Colonization and infection by extended spectrum bet a-lactamase producing enterobacteriaceae (ESBL-E) increasingly affect subjects in community. The prevalence of carriage in the community has been estimated at 30 and 70% respectively in Africa and Asia, while it is only 10% in Europe. Living or visiting areas with high endemicity is therefore a high risk factor for ESBL-E acquisition. ESBL-E prevalence carriage in intertropical areas and the risk factors for acquisition by an individual subject when exposed to such environments have been widely studied, but the issue of secondary transmissions from these index cases has not been addressed, although it is essential, in particular to understand its impact on the spread of ESBL-E in the community. We studied the acquisition and transmission of ESBL-E in two cohorts of subjects living in highly endemic areas in promiscuity, with other individuals at the time of acquisition. For this purpose, we used PCR and whole genome sequencing (WGS) techniques, combined with a fine analysis of single nucleotide polymorphisms (SNPs). The first cohort was composed of soldiers on mission in 3 different regions, Afghanistan, Guyana andCôte d'Ivoire. The ESBL-E acquisition rates during the mission varied depending on the destination: 88% in Afghanistan, 49% in Côte d'Ivoire and 5% in Guyana. The transmission of ESBL E. coli between soldiers, studied within the Afghan company, did not evidence any transmission of strains in this company. The good hygienic conditions in the camp and the limited contact with the local population would suggest that the high acquisition rate observed could be due to individual acquisition, based on meals purchased regularly from the many street vendors installed around thecamp. The second cohort was based on a placebo-controlled study on malnourished, outpatient children living in Niger. The objective of this work was to evaluate the impact of amoxicillin administered systematically in renutrition protocols for severely malnourished children, on ESBL-E colonization and on strain transmission in siblings. We observed that the administration of amoxicillin increased the risk of ESBL-E acquisition in the treated child within one week of treatment(54% vs. 32%, p<0.001) and the risk of ESBL transmission in the siblings (11.5% vs. 3.8%, p=0.04). In total, in these two studies, we showed that the complete characterization of strains by WGS and SNP analysis provided essential information to understand the dynamics of ESBL-E sharing between subjects.These studies provide some answers on the ESBL-E transmission in the community and the associated risk factors, but other risk factors and situations still need to be explored with these new tools

Contribution des D,D-carboxypeptidases dans la synthèse du peptidoglycane et la résistance aux bêta-lactamines chez Mycobacterium tuberculosis

PARIS-BIUP (751062107) / SudocSudocFranceF

In vitro bactericidal activity of amoxicillin combined with different cephalosporins against endocarditis-associated Enterococcus faecalis clinical isolates

International audienceBackground - The combination of amoxicillin with cefazolin could be an interesting regimen for the empirical therapy of severe infective endocarditis, but its activity against enterococci is unknown. Objectives - To evaluate in vitro the bactericidal activity of the combination of amoxicillin with different cephalosporins including cefazolin. Methods - Combinations of amoxicillin (at MIC×¼) with cefazolin, cefotaxime, ceftriaxone, cefepime, ceftaroline or ceftobiprole (at the mean free plasma concentration) were studied using time-kill experiments for 10 endocarditis-associated Enterococcus faecalis strains and 2 reference strains. Results - The combinations amoxicillin/cefazolin, amoxicillin/cefotaxime, amoxicillin/ceftriaxone and amoxicillin/cefepime were synergistic at 12 and 24 h against 12/12 strains and amoxicillin/ceftobiprole and amoxicillin/ceftaroline against 10/12 strains. The combination amoxicillin/cefepime was bactericidal at 24 h against 9/12 strains, the combination amoxicillin/cefazolin against 8/12 strains, the combinations amoxicillin/ceftaroline, amoxicillin/cefotaxime and amoxicillin/ceftobiprole against 7/12 strains and the combination amoxicillin/ceftriaxone against 6/12 strains. Conclusions - The combination amoxicillin/cefazolin is as synergistic and bactericidal in vitro as amoxicillin/cefotaxime or amoxicillin/ceftriaxone against E. faecalis

Acquisition of plasmid-mediated cephalosporinase producing Enterobacteriaceae after a travel to the tropics

International audienceTravelers are at high risk of acquiring multi-drug resistant Enterobacteriaceae (MRE) while traveling abroad. Acquisition of extended spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) while traveling has been extensively described, but not that of plasmid-mediated cephalosporinase producing Enterobacteriaceae (pAmpC-E). Here, we characterized the pAmpC-E acquired in 574 French travelers to tropical areas enrolled in the VOYAG-R study. Among the 526 MRE isolated at return, 57 (10.8%) from 49 travelers were pAmpC-E. The acquisition rate of pAmpC-E was 8.5% (49/574) ranging from 12.8% (25/195) in Asia, 7.6% (14/184) in Latin America to 5.1% (10/195) in Africa. The highest acquisition rates were observed in Peru (21.9%), India (21.4%) and Vietnam (20%). The carriage of pAmpC-E decreased quickly after return with 92.5% of colonized travelers being negative at one month. Most enzymes were CMY types (96.5%, n = 55, only met in Escherichia coli), including 40 CMY-2 (70.2%), 12 CMY-42 (21.1%), 1 CMY-6 and two new CMY-2 variants. The remaining were two DHA observed in Klebsiella pneumoniae. CMY-2 producing strains were acquired worldwide whereas CMY-42, except for one, were all acquired in Asia. BlaCMY-2 genes were associated with different plasmid types, including IncI1 (45. 2%), IncF (10%), IncF-IncI (7.5%), IncA/C (5%) and IncR (2.5%) whereas blaCMY-42 were all associated with IncI1 plasmids. Even though the pAmpC-E acquisition rate was much lower than that of ESBL-E, it was significant, especially in Asia, showing that pAmpC-E, especially CMY-type producing E. coli have spread in the community settings of tropical regions

High acquisition rate of extended-spectrum β-lactamase-producing Enterobacteriaceae among French military personnel on mission abroad, without evidence of inter-individual transmission

International audienceOBJECTIVES:Acquisition of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) by Europeans travelling individually in high-endemicity countries is common. However, how the different ESBL-E strains circulate in groups of travellers has not been studied. We investigated ESBL-E transmission within several groups of French military personnel serving overseas for 4-6 months.METHODS:We conducted a prospective study among French military personnel assigned to Afghanistan, French Guiana or Côte d'Ivoire for 4-6 months. Faecal samples provided by volunteers before leaving and after returning were screened for ESBL-E isolates. ESBL Escherichia coli from each military group was characterized by repetitive element palindromic polymerase chain reaction (rep-PCR) fingerprinting followed, in the Afghanistan group, by whole-genome sequencing (WGS) if similarity was ≥97%.RESULTS:Among the 189 volunteers whose samples were negative before departure, 72 (38%) were positive after return. The highest acquisition rates were observed in the Afghanistan (29/33, 88%) and Côte d'Ivoire (39/80, 49%) groups. Acquisition rates on return from French Guiana were much lower (4/76, 5%). WGS of the 20 strains from the Afghanistan group that clustered by rep-PCR identified differences in sequence type, serotype, resistance genes and plasmid replicons. Moreover, single-nucleotide polymorphism (SNP) differences across acquired strains from a given cluster ranged from 30 to 3641, suggesting absence of direct transmission.CONCLUSIONS:ESBL-E. coli acquisition was common among military personnel posted overseas. Many strains clustered by rep-PCR but differed by WGS and SNP analysis, suggesting acquisition from common external sources rather than direct person-to-person transmission

Two original observations concerning bacterial infections in COVID-19 patients hospitalized in intensive care units during the first wave of the epidemic in France.

Among 197 COVID-19 patients hospitalized in ICU, 88 (44.7%) experienced at least one bacterial infection, with pneumonia (39.1%) and bloodstream infections (15,7%) being the most frequent. Unusual findings include frequent suspicion of bacterial translocations originating from the digestive tract as well as bacterial persistence in the lungs despite adequate therapy

Very high prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae in bacteriemic patients hospitalized in teaching hospitals in Bamako, Mali.

The worldwide dissemination of extended-spectrum beta-lactamase producing Enterobacteriaceae, (ESBL-E) and their subset producing carbapenemases (CPE), is alarming. Limited data on the prevalence of such strains in infections from patients from Sub-Saharan Africa are currently available. We determined, here, the prevalence of ESBL-E/CPE in bacteriemic patients in two teaching hospitals from Bamako (Mali), which are at the top of the health care pyramid in the country. During one year, all Enterobacteriaceae isolated from bloodstream infections (E-BSI), were collected from patients hospitalized at the Point G University Teaching Hospital and the pediatric units of Gabriel Touré University Teaching Hospital. Antibiotic susceptibility testing, enzyme characterization and strain relatedness were determined. A total of 77 patients had an E-BSI and as many as 48 (62.3%) were infected with an ESBL-E. ESBL-E BSI were associated with a previous hospitalization (OR 3.97 95% IC [1.32; 13.21]) and were more frequent in hospital-acquired episodes (OR 3.66 95% IC [1.07; 13.38]). Among the 82 isolated Enterobacteriaceae, 58.5% were ESBL-E (20/31 Escherichia coli, 20/26 Klebsiella pneumoniae and 8/15 Enterobacter cloacae). The remaining (5 Salmonella Enteritidis, 3 Morganella morganii 1 Proteus mirabilis and 1 Leclercia adecarboxylata) were ESBL negative. CTX-M-1 group enzymes were highly prevalent (89.6%) among ESBLs; the remaining ones being SHV. One E. coli produced an OXA-181 carbapenemase, which is the first CPE described in Mali. The analysis of ESBL-E relatedness suggested a high rate of cross transmission between patients. In conclusion, even if CPE are still rare for the moment, the high rate of ESBL-BSI and frequent cross transmission probably impose a high medical and economic burden to Malian hospitals

Risks factor for ESBL producing <i>Enterobacteriaceae</i> bloodstream infections.

<p>Risks factor for ESBL producing <i>Enterobacteriaceae</i> bloodstream infections.</p

Performance evaluation of a PCR panel (FilmArray® Pneumonia Plus) for detection of respiratory bacterial pathogens in respiratory specimens: A systematic review and meta-analysis

International audienceBackground: Accuracy and timing of antibiotic therapy remain a challenge for lower respiratory tract infections. New molecular techniques using Multiplex Polymerase Chain Reaction, including the FilmArray® Pneumonia Plus Panel [FAPP], have been developed to address this. The aim of this study is to evaluate the FAPP diagnostic performance for the detection of the 15 typical bacteria of the panel from respiratory samples in a meta-analysis from a systematic review. Methods: We searched PubMed and EMBASE from January 1, 2010, to December 31, 2022, and selected any study on the FAPP diagnostic performance on respiratory samples compared to the reference standard, bacterial culture. The main outcome was the overall diagnostic accuracy with sensitivity and specificity. We calculated the log Diagnostic Odds Ratio and analyzed performance for separate bacteria, antimicrobial resistance genes, and according to the sample type. We also reported the FAPP turnaround time and the out-of-panel bacteria number and species. This study is registered with PROSPERO (CRD42021226280). Results: From 10 317 records, we identified 30 studies including 8 968 samples. Twenty-one were related to intensive care. The overall sensitivity and specificity were 94% [95% Confidence Interval (CI) 91–95] and 98% [95%CI 97–98], respectively. The log Diagnostic Odds Ratio was 6.35 [95%CI 6.05–6.65]. 9.3% [95%CI 9.2–9.5] of bacteria detected in culture were not included in the FAPP panel. Conclusion: This systematic review reporting the FAPP evaluation revealed a high accuracy. This test may represent an adjunct tool for pulmonary bacterial infection diagnostic and antimicrobial stewardship. Further evidence is needed to assess the impact on clinical outcome. © 2023 Société française d&#039;anesthésie et de réanimation (Sfar

Genetic relatedness (Rep-PCR) between ESBL producing <i>Enterobacteriaceae</i> isolated from bacteriemic patients hospitalized in referral centers in Bamako (Mali).

<p>(a) ESBL-producing <i>E</i>. <i>coli</i>, n = 20. (<b>b</b>) ESBL-producing <i>K</i>. <i>pneumonia</i>, n = 20 and (<b>c</b>) ESBL-producing <i>E</i>. <i>cloacae</i>, <i>n = 8</i>. PG = Point G University teaching hospital (adults), GT = Gabriel Touré University teaching hospital (pediatric).</p