High Heterogeneity of Multidrug-Resistant Enterobacteriaceae Fecal Levels in Hospitalized Patients Is Partially Driven by Intravenous β-Lactams - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Accéder directement au contenu
Article Dans Une Revue Antimicrobial Agents and Chemotherapy Année : 2020

High Heterogeneity of Multidrug-Resistant Enterobacteriaceae Fecal Levels in Hospitalized Patients Is Partially Driven by Intravenous β-Lactams

Ana Djukovic
  • Fonction : Auteur
Eva González-Barberá
  • Fonction : Auteur
Jaime Sanz
Alejandro Artacho
  • Fonction : Auteur
Iván Peñaranda
  • Fonction : Auteur
María José Garzón
  • Fonction : Auteur
Miguel Salavert
  • Fonction : Auteur
José Luis López-Hontangas
  • Fonction : Auteur
Karina Xavier
  • Fonction : Auteur
Bernhard Kuster
  • Fonction : Auteur
Laurent Debrauwer
Carles Ubeda
  • Fonction : Auteur

Résumé

Multidrug-resistant Enterobacteriaceae (MRE) colonize the intestine asymptomatically from where they can breach into the bloodstream and cause life-threatening infections, especially in heavily colonized patients. Despite the clinical relevance of MRE colonization levels, we know little about how they vary in hospitalized patients and the clinical factors that determine those levels. Here we conducted one of the largest studies of MRE fecal levels by tracking longitudinally 133 acute leukemia patients and monitoring their MRE levels over time through extensive culturing. MRE were defined as Enterobactericeae species that acquired non-susceptibility to ≥1 agent in ≥3 antimicrobial categories. In addition, due to the selective media used, the MRE had to be resistant to third-generation cephalosporins. MRE were detected in 60% of the patients, but their fecal levels varied considerably among patients and within the same patient (>6 and 4 orders of magnitude, respectively). Multivariate analysis of clinical metadata revealed an impact of intravenous beta-lactams (i.e. meropenem and piperacillin-tazobactam), which significantly diminished the fecal MRE levels in hospitalized patients. Consistent with a direct action of beta-lactams, we found an effect only when the patient was colonized with strains sensitive to the administered beta-lactam (p<0.001) but not with non-susceptible strains. We report previously unobserved inter and intra-individual heterogeneity in MRE fecal levels, suggesting that quantitative surveillance is more informative than qualitative surveillance of hospitalized patients. In addition, our study highlights the relevance of incorporating antibiotic treatment and susceptibility data of gut colonizing pathogens for future clinical studies and in clinical decision-making.
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Dates et versions

hal-02465857 , version 1 (26-05-2020)

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Ana Djukovic, Eva González-Barberá, Jaime Sanz, Alejandro Artacho, Iván Peñaranda, et al.. High Heterogeneity of Multidrug-Resistant Enterobacteriaceae Fecal Levels in Hospitalized Patients Is Partially Driven by Intravenous β-Lactams. Antimicrobial Agents and Chemotherapy, 2020, 64 (2), 33 p. ⟨10.1128/AAC.01415-19⟩. ⟨hal-02465857⟩
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