Antiobiotiques et antibiorésistance, un avatar singulier de l’histoire planétaire

La résistance des bactéries aux antibiotiques est le résultat d’un processus d’adaptation très ancien, accéléré par les usages immodérés des antibiotiques au xxe siècle, tant en ce qui concerne la santé humaine, que la santé animale. Ce phénomène constitue une menace majeure pour la médecine dont les pratiques et les avancées se trouvent ainsi remises en question. Le problème a aussi des aspects globaux et systémiques car la résistance des bactéries a suivi les évolutions économiques et géopolitiques des xxe et xxie siècles. Elle prend, de nos jours, une ampleur particulière du fait de la globalisation économique ainsi que des échanges touristiques et médicaux.Antibioresistance is the result of a long term process accelerated by the misuse of antibiotics in human and animal health through the 20th century. This phenomenon is a major threat for the medical practices which developments are now questioned. The problem also, has global and systemic aspects because the antibioresistance has followed the economic and political evolutions of the 20th and 21th centuries. Its developments today, are the results of new global economic, medical and touristic exchanges

Massive Increase, Spread, and Exchange of Extended Spectrum {beta}-Lactamase-Encoding Genes Among Intestinal Enterobacteriaceae in Hospitalized Children With Severe Acute Malnutrition in Niger.

Background. From the time of CTX-M emergence, extended-spectrum β-lactamase-producing enterobacteria (ESBL-E) have spread worldwide in community settings as well as in hospitals, particularly in developing countries. Although their dissemination appears linked to Escherichia coli intestinal carriage, precise paths of this dynamic are largely unknown. Methods. Children from a pediatric renutrition center were prospectively enrolled in a fecal carriage study. Antibiotic exposure was recorded. ESBL-E strains were isolated using selective media from fecal samples obtained at admission and, when negative, also at discharge. ESBL-encoding genes were identified, their environments and plasmids were characterized, and clonality was assessed with polymerase chain reaction-based methods and pulsed-field gel electrophoresis for E. coli and Klebsiella pneumoniae. E. coli strains were subjected to multilocus sequence typing. Results. The ESBL-E carriage rate was 31% at admission in the 55 children enrolled. All children enrolled received antibiotics during hospitalization. Among the ESBL-E-negative children, 16 were resampled at discharge, and the acquisition rate was 94%. The bla(CTX-M-15) gene was found in >90% of the carriers. Genetic environments and plasmid characterization evidenced the roles of a worldwide, previously described, multidrug-resistant region and of IncF plasmids in CTX-M-15 E. coli dissemination. Diversity of CTX-M-15-carrying genetic structures and clonality of acquired ESBL E. coli suggested horizontal genetic transfer and underlined the potential of some ST types for nosocomial cross-transmission. Conclusions. Cross-transmission and high selective pressure lead to very high acquisition of ESBL-E carriage, contributing to dissemination in the community. Strict hygiene measures as well as careful balancing of benefit-risk ratio of current antibiotic policies need to be reevaluated

Introduction of highly resistant bacteria into a hospital via patients repatriated or recently hospitalized in a foreign country

AbstractWe describe the prevalence of carriage and variables associated with introduction of highly drug-resistant microorganisms (HDRMO) into a French hospital via patients repatriated or recently hospitalized in a foreign country. The prevalence of HDRMO was 11% (15/132), with nine carbapenamase-producing Enterobacteriaceae, nine carbapenem-resistant Acinetobacter baumannii and six glycopeptide-resistant enterococci. Half of the admitted patients (63/132, 48%) were colonized with extended spectrum beta-lactamase-producing Enterobacteriaceae (ESBLPE). Among the four episodes with secondary cases, three involved A. baumannii

Decolonization of intestinal carriage of extended-spectrum β-lactamase-producing Enterobacteriaceae with oral colistin and neomycin: a randomized, double-blind, placebo-controlled trial

Objectives Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) are an increasingly frequent cause of infections in the community and the healthcare setting. In this study, we aimed to investigate whether intestinal carriage of ESBL-E can be eradicated. Methods We conducted a double-blind, randomized, placebo-controlled, single-centre trial to assess the efficacy of an oral decolonization regimen on intestinal ESBL-E carriage in adult patients with an ESBL-E-positive rectal swab. Fifty-eight patients were allocated 1 : 1 to either placebo or colistin sulphate (50 mg 4×/day) and neomycin sulphate (250 mg 4×/day) for 10 days plus nitrofurantoin (100 mg 3×/day) for 5 days in the presence of ESBL-E bacteriuria. The primary outcome was detection of ESBL-E by rectal swab 28 ± 7 days after the end of treatment. Missing primary outcome data were imputed based on the last available observation. Additional cultures (rectal, inguinal and urine) were taken on day 6 of treatment and on days 1 and 7 post-treatment. The study protocol has been registered with ClinicalTrials.gov (NCT00826670). Results Among 54 patients (27 in each group) included in the primary analysis, there was no statistically significant difference between the groups with regard to the primary outcome [14/27 (52%) versus 10/27 (37%), P = 0.27]. During treatment and shortly afterwards, there was significantly lower rectal ESBL-E carriage in the treatment group: 9/26 versus 19/22 on day 6 of treatment (P < 0.001) and 8/25 versus 20/26 on day 1 post-treatment (P = 0.001). This effect had disappeared by day 7 post-treatment (18/27 versus 17/25, P = 0.92). Liquid stools were more common in the treatment group (7/27 versus 2/29, P = 0.05). Conclusions The regimen used in this study temporarily suppressed ESBL-E carriage, but had no long-term effec

Staphylococus aureus ST398: a medical paradigm of the 21st century

The potential for nasal and pharyngeal colonization by the bacterial species, Staphylococcus aureus, has increased over the last decade, particularly among pigs. The frequency of Methicillin-Resistant Staphylococcus aureus (MRSA) strains varies, but they constitute a non-negligible risk for those involved in pig production, i.e. pig-keepers, veterinarians, and slaughterhouse workers. Molecular identification by MLST (Multi Locus Sequence Typing) of isolates originally non-typeable (NT) by Pulse Field Electrophoresis clearly showed the predominance in Europe, North America and Asia of the ST398 (CC398) type. So far, this strain does not appear to be highly resistant to antibiotics, with the exception of tetracyclines, and perhaps macrolides, nor does it produce the virulence factors generally associated with CA-MRSA, such as the Panton-Valentine leukocidin. Various types of human infection were reported in several European countries, producing skin and mucous membranes, lungs, endocardium and bacteremic infections. Some experts suggest that, despite their low riskL’espèce Staphylococcus aureus a montré, au cours de ces dernières années, un fort pouvoir de colonisation naso-pharyngée, en particulier chez le porc. Le pourcentage de souches résistantes intrinsèques ou SAMR est variable mais le risque de colonisation est non négligeable pour les professionnels de la filière de production porcine, tels que les porchers, vétérinaires, employés d’abattoir. L’identification moléculaire par la technique de Multi Locus Sequence Typing (MLST) de souches initialement non typables (NT) par l’électrophorèse en champ pulsé indique la prédominance, aussi bien en Europe, en Amérique du Nord qu’en Asie, du type ST398 (ou CC398). Cette souche est encore peu résistante aux antibiotiques, à l’exception des tétracyclines, voire des macrolides et ne produit pas les facteurs de virulence rapportés habituellement chez le CA-MRSA, tels que la leucocidine de Panton- Valentine. Divers types d’infection sont maintenant rapportés chez l’homme dans plusieurs pays européens : infections cutanéo-muqueuses, pulmonaires, bactériémiques et endocardites. Des spécialistes évoquent, pour ces souches d’origine animale (LA pour Lifestock-Associated), l’éventualité « d’une nouvelle zoonose » malgré leur faible diffusion chez l’homme

Rapid detection of glycopeptide-resistant enterococci: impact on decision-making and costs.

International audienceBACKGROUND: According to French national recommendations, the detection of a patient colonized with glycopeptide-resistant enterococci (GRE) leads to interruption of new admissions and transfer of contact patients (CPs) to another unit or healthcare facility, with weekly screening of CPs. FINDINGS: We evaluated the medical and economic impact of a pragmatic adaptation of national guidelines associated with a real-time PCR (RTP) (Cepheid XpertTM vanA/vanB) as part of the strategy for controlling GRE spread in two medical wards. Screening was previously performed using chromogenic selective medium (CSM). Turn around time (TAT), costs of tests and cost of missed patient days were prospectively collected. In February 2012, the identification of GRE in one patient in the diabetology ward led to the screening of 31 CPs using CSM; one secondary case was identified in a CP already transferred to the Nephrology ward. Awaiting the results of SCM (median TAT, 70.5 h), 41 potential patient days were missed, due to interruption of admissions. The overall cost (screening tests + missing patient.days) was estimated at 14, 302.20 [euro sign]. The secondary case led to screening of 22 CPs in the Nephrology ward using RTP. Because of a short median TAT of 4.6 h, we did not interrupt admissions and patients' transfers. Among 22 CPs, 19 (86%) were negative for vanA, 2 were positive for vanB and 3 had invalid results needing CSM. The overall cost of the strategy was estimated at 870.40 [euro sign] (cost of screening tests only), without missing patient days. CONCLUSION: The rapid PCR test for vanA-positive GRE detection both allowed rapid decision about the best infection control strategy and prevented loss of income due to discontinuation of patient transfers and admissions

Escherichia coli population structure and antibiotic resistance at a buffalo/cattle interface in Southern Africa

At a human/livestock/wildlife interface, Escherichia coli populations were used to assess the risk of bacterial and antibiotic resistance dissemination between hosts. We used phenotypic and genotypic characterization techniques to describe the structure and the level of antibiotic resistance of E. coli commensal populations and the resistant Enterobacteriaceae carriage of sympatric African buffalo (Syncerus caffer caffer) and cattle populations characterized by their contact patterns in the southern part of Hwange ecosystem in Zimbabwe. Our results (i) confirmed our assumption that buffalo and cattle share similar phylogroup profiles, dominated by B1 (44.5%) and E (29.0%) phylogroups, with some variability in A phylogroup presence (from 1.9 to 12%); (ii) identified a significant gradient of antibiotic resistance from isolated buffalo to buffalo in contact with cattle and cattle populations expressed as the Murray score among Enterobacteriaceae (0.146, 0.258, and 0.340, respectively) and as the presence of tetracycline-, trimethoprim-, and amoxicillin-resistant subdominant E. coli strains (0, 5.7, and 38%, respectively); (iii) evidenced the dissemination of tetracycline, trimethoprim, and amoxicillin resistance genes (tet, dfrA, and blaTEM-1) in 26 isolated subdominant E. coli strains between nearby buffalo and cattle populations, that led us (iv) to hypothesize the role of the human/animal interface in the dissemination of genetic material from human to cattle and toward wildlife. The study of antibiotic resistance dissemination in multihost systems and at anthropized/natural interface is necessary to better understand and mitigate its multiple threats. These results also contribute to attempts aiming at using E. coli as a tool for the identification of pathogen transmission pathway in multihost systems. (Résumé d'auteur

Veterinary Medicine Needs New Green Antimicrobial Drugs

Given that: (1) the worldwide consumption of antimicrobial drugs (AMDs) used in food-producing animals will increase over the coming decades; (2) the prudent use of AMDs will not suffice to stem the rise in human antimicrobial resistance (AMR) of animal origin; (3) alternatives to AMD use are not available or not implementable, there is an urgent need to develop novel AMDs for food-producing animals. This is not for animal health reasons, but to break the link between human and animal resistomes. In this review we establish the feasibility of developing for veterinary medicine new AMDs, termed green antibiotics, having minimal ecological impact on the animal commensal and environmental microbiomes.We first explain why animal and human commensal microbiota comprise a turnstile exchange, between the human and animal resistomes. We then outline the ideal physico-chemical, pharmacokinetic and pharmacodynamic properties of a veterinary green antibiotic and conclude that they can be developed through a rational screening of currently used AMD classes. The ideal drug will be hydrophilic, of relatively low potency, slow clearance and small volume of distribution. It should be eliminated principally by the kidney as inactive metabolite(s). For oral administration, bioavailability can be enhanced by developing lipophilic pro-drugs. For parenteral administration, slow-release formulations of existing eco-friendly AMDs with a short elimination half-life can be developed. These new eco-friendly veterinary AMDs can be developed from currently used drug classes to provide alternative agents to those currently used in veterinary medicine and mitigate animal contributions to the human AMR problem