Unexpected persistence of extended-spectrum β-lactamase-producing Enterobacteriaceae in the faecal microbiota of hospitalised patients treated with imipenem.
Grall NINSERM, IAME, UMR 1137, F-75018 Paris, France; Université Paris-Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France; AP-HP, Hôpital Bichat, Laboratoire de Microbiologie, F-75018 Paris, France. Electronic address: nathalie.grall@aphp.fr.
Lazarevic VGenomic Research Laboratory, Geneva University Hospitals, Geneva, Switzerland.
Gaïa NGenomic Research Laboratory, Geneva University Hospitals, Geneva, Switzerland.
Couffignal CINSERM, IAME, UMR 1137, F-75018 Paris, France; Université Paris-Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France; AP-HP, Hôpital Bichat, Service de Biostatistique, F-75018 Paris, France.
Laouénan CINSERM, IAME, UMR 1137, F-75018 Paris, France; Université Paris-Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France; AP-HP, Hôpital Bichat, Service de Biostatistique, F-75018 Paris, France.
Ilic-Habensus EAP-HP, Hôpital Bichat, INSERM CIC 1425, F-75018 Paris, France.
Wieder IAP-HP, Hôpital Bichat, Laboratoire de Microbiologie, F-75018 Paris, France.
Plesiat PLaboratoire de Bactériologie EA4266, Faculté de Médecine-Pharmacie, Université de Franche-Comté, Besançon, France.
Angebault CAP-HP, Hôpital Necker-Enfants Malades, Unité de Parasitologie-Mycologie, Service de Microbiologie, F-75015 Paris, France; Université Paris Descartes, Sorbonne Paris-Cité, F-75015 Paris, France.
Bougnoux MEAP-HP, Hôpital Necker-Enfants Malades, Unité de Parasitologie-Mycologie, Service de Microbiologie, F-75015 Paris, France; Université Paris Descartes, Sorbonne Paris-Cité, F-75015 Paris, France.
Armand-Lefevre LINSERM, IAME, UMR 1137, F-75018 Paris, France; Université Paris-Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France; AP-HP, Hôpital Bichat, Laboratoire de Microbiologie, F-75018 Paris, France.
Andremont AINSERM, IAME, UMR 1137, F-75018 Paris, France; Université Paris-Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France; AP-HP, Hôpital Bichat, Laboratoire de Microbiologie, F-75018 Paris, France.
Duval XINSERM, IAME, UMR 1137, F-75018 Paris, France; Université Paris-Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France; AP-HP, Hôpital Bichat, INSERM CIC 1425, F-75018 Paris, France.
Schrenzel JGenomic Research Laboratory, Geneva University Hospitals, Geneva, Switzerland; Laboratory of Bacteriology, Geneva University Hospitals, Geneva, Switzerland.
English
Imipenem is active against extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) but favours the intestinal emergence of resistance. The effects of imipenem on intestinal microbiota have been studied using culture-based techniques. In this study, the effects were investigated in patients using culture and metagenomic techniques. Seventeen hospitalised adults receiving imipenem were included in a multicentre study (NCT01703299, http://www.clinicaltrials.gov). Most patients had a history of antibiotic use and/or hospitalisation. Stools were collected before, during and after imipenem treatment. Bacterial and fungal colonisation was assessed by culture, and microbiota changes were assessed using metagenomics. Unexpectedly, high colonisation rates by imipenem-susceptible ESBL-E before treatment (70.6%) remained stable over time, suggesting that imipenem intestinal concentrations were very low. Carriage rates of carbapenem-resistant Gram-negative bacilli (0-25.0%) were also stable over time, whereas those of yeasts (64.7% before treatment) peaked at 76.5% during treatment and decreased thereafter. However, these trends were not statistically significant. Yeasts included highly diverse colonising Candida spp. Metagenomics showed no global effect of imipenem on the bacterial taxonomic profiles at the sequencing depth used but demonstrated specific changes in the microbiota not detected with culture, attributed to factors other than imipenem, including sampling site or treatment with other antibiotics. In conclusion, culture and metagenomics were highly complementary in characterising the faecal microbiota of patients. The changes observed during imipenem treatment were unexpectedly limited, possibly because the microbiota was already disturbed by previous antibiotic exposure or hospitalisation.