High Heterogeneity of Multidrug-Resistant Enterobacteriaceae Fecal Levels in Hospitalized Patients Is Partially Driven by Intravenous β-Lactams - Aix-Marseille Université Access content directly
Journal Articles Antimicrobial Agents and Chemotherapy Year : 2020

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

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

Abstract

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 and 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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