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

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

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

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

Effect of human vicinity on antimicrobial resistance and integrons in animal faecal Escherichia coli”.

Objectives: To determine the level of antimicrobial resistance and the occurrence of class 1, 2 and 3 integrons in faecal Escherichia coli from several animal populations variously exposed to human contact. Methods: A collection of 341 faecal E. coli isolates was constituted from several animal populations subject to various degrees of exposure to humans: 18 animals never exposed to humans (living in the Antarctic or Gabon), 71 wild animals living in a low human density area (mountainous region of the Pyrenees, France), 61 wild animals living in a higher human density area (Fontainebleau forest near Paris, France), and 128 extensively reared farm animals and 42 pet dogs, both living in the Pyrenees. Resistance to antimicrobial agents was determined by the method of disc diffusion and quantified using the resistance score of BE Murray, JJ Mathewson, HL DuPont, CD Ericsson and RR Reves (Antimicrobial Agents and Chemotherapy 1990; 34: 515-18). Integrons were characterized by triplex realtime PCR and sequencing. The absence of epidemiologic clones was confirmed by PCR-based methods. Results: A gradient of resistance ranging from absence to high prevalence (resistance score of 18.7%) and a gradual increase in the prevalence of class 1 integrons (from 0% to 16%), both correlated with the increase in exposure to humans, were observed. In wild animals with little contact with humans, resistance, when present, was not mediated by integrons. Conclusions: Our findings firmly establish that the current prevalence of antimicrobial resistance found in animal faecal bacteria, as well as the prevalence of integrons, is clearly anthropogenic. The presence of integrons may constitute an adaptive process to environments whose antimicrobial pressure exceeds a certain threshold

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

High prevalence of the arginine catabolic mobile element in carriage isolates of methicillin-resistant Staphylococcus epidermidis

Background The arginine catabolic mobile element (ACME) associated with staphylococcal cassette chromosome mec (SCCmec) in the USA300 clone of community-acquired methicillin-resistant Staphylococcus aureus enhances its fitness and ability to colonize the host. Staphylococcus epidermidis may act as a reservoir of ACME for S. aureus. We assessed the diffusion of ACME in methicillin-resistant S. epidermidis (MRSE) isolates colonizing outpatients. Methods Seventy-eight MRSE strains isolated in outpatients from five countries were characterized by multilocus sequence typing (MLST) and SCCmec typing and screened for the arcA and opp3AB markers of ACME. ACME-arcA and ACME-opp3AB were sequenced. ACME type I from MRSE and USA300 were compared by long-range PCR (LR-PCR). Results Fifty-three (67.9%) MRSE strains carried an ACME element, including 19 (24.4%), 32 (41.0%) and 2 (2.6%) with ACME type I (arcA+/opp3AB+), II (arcA+/opp3AB−) and III (arcA−/opp3AB+), respectively. The prevalence of ACME did not differ between clonal complex 2 (42/60 strains) and other sequence types (11/18 strains, P = 0.7), with MLST data suggesting frequent intraspecies acquisition. ACME-arcA sequences were highly conserved, whereas ACME-opp3AB displayed 11 distinct allotypes. ACME was found in 14/29, 9/11 and 30/37 strains with type IV, type V and non-typeable SCCmec, respectively (P = 0.01). ACME was more frequently associated with ccrC than with ccrAB2 (82.4% versus 60.0%, P = 0.048). LR-PCR indicated structural homologies of ACME I between MRSE and USA300. Conclusions ACME is widely disseminated in MRSE strains colonizing outpatients and may contribute to their spread in a community environment with low antibiotic exposure, as suggested for USA30

Methicillin-Resistant Coagulase-Negative Staphylococci in the Community: High Homology of SCCmec IVa between Staphylococcus epidermidis and Major Clones of Methicillin-Resistant Staphylococcus aureus

Background. Data on community spread of methicillin-resistant coagulase-negative staphylococci (MR-CoNS) are scarce. We assessed their potential role as a reservoir of staphylococcal cassette chromosome mec (SCCmec) IVa, the leading SCCmec subtype in community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Methods. Nasal carriage of MR-CoNS was prospectively investigated in 291 adults at hospital admission. MR-CoNS were characterized by SCCmec typing, long-range polymerase chain reaction (PCR) for SCCmec IV, and multiple-locus variable-number tandem repeat analysis (MLVA) for Staphylococcus epidermidis (MRSE) strains. Three SCCmec IVa elements were fully sequenced. Results. The carriage rate of MR-CoNS was 19.2% (25.9% and 16.5% in patients with and patients without previous exposure to the health care system, respectively; P = .09). MR-CoNS strains (n=83, including 58 MRSE strains with highly heterogeneous MLVA patterns) carried SCCmec type IVa (n=9, all MRSE), other SCCmec IV subtypes (n=9, including 7 MRSE), other SCCmec types (n=15), and nontypeable SCCmec (n=50). Long-range PCR indicated structural homology between SCCmec IV in MRSE and that in MRSA. Complete sequences of SCCmec IVa from 3 MRSE strains were highly homologous to those available for CA-MRSA, including major clones USA300 and USA400. Conclusions. MR-CoNS are probably disseminated in the community, notably in subjects without previous exposure to the health care system. MRSE, the most prevalent species, may act as a reservoir of SCCmec IVa for CA-MRS

Escherichia coli as Reservoir for Macrolide Resistance Genes

The plasmid-borne mph(A) gene that confers resistance to azithromycin and has recently emerged in Shigella sonnei is present in multidrug- and non–multidrug-resistant Escherichia coli isolates from 4 continents. Further spread of mph(A) to Shigella and Salmonella spp. may be expected