High Heterogeneity of Multidrug-Resistant Enterobacteriaceae Fecal Levels in Hospitalized Patients Is Partially Driven by Intravenous ß-Lactams
Por:
Djukovic A, González-Barberá EM, Sanz J, Artacho A, Peñaranda I, Herrera B, Garzón MJ, Salavert M, López-Hontangas JL, Xavier KB, Kuster B, Debrauwer L, Rolain JM, Sanz M, Xavier J and Ubeda C
Publicada:
1 feb 2020
Ahead of Print:
27 ene 2020
Resumen:
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 Enterobacteriaceae species that acquired nonsusceptibility to >= 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 betalactam (P < 0.001) but not with nonsusceptible strains. We report previously unobserved inter- and intraindividual 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.
Filiaciones:
:
Centro Superior de Investigación en Salud Pública - FISABIO, Valencia, Spain
González-Barberá EM:
Hospital Universitari I Politècnic La Fe, Valencia, Spain
Sanz J:
Hospital Universitari I Politècnic La Fe, Valencia, Spain
CIBERONC, Instituto Carlos III, Madrid, Spain
:
Centro Superior de Investigación en Salud Pública - FISABIO, Valencia, Spain
:
Centro Superior de Investigación en Salud Pública - FISABIO, Valencia, Spain
:
Centro Superior de Investigación en Salud Pública - FISABIO, Valencia, Spain
:
Centro Superior de Investigación en Salud Pública - FISABIO, Valencia, Spain
Salavert M:
Hospital Universitari I Politècnic La Fe, Valencia, Spain
López-Hontangas JL:
Hospital Universitari I Politècnic La Fe, Valencia, Spain
Xavier KB:
Instituto Gulbenkian de Ciência, Oeiras, Portugal
Kuster B:
Chair of Proteomics and Bioanalytics, Technical University of Munich, Fresing, Germany
Debrauwer L:
Toxalim, Université de Toulouse, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, F-31027 Toulouse, France
Axiom Platform, UMR 1331 Toxalim, MetaToul-MetaboHUB, National Infrastructure of Metabolomics and Fluxomics, F-31027 Toulouse, France
Rolain JM:
Aix Marseille Univ, IRD, APHM, MEPHI, IHU-Méditerranée Infection, Marseille, France
Sanz M:
Hospital Universitari I Politècnic La Fe, Valencia, Spain
CIBERONC, Instituto Carlos III, Madrid, Spain
Xavier J:
Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Computational Biology Program, Sloan-Kettering Institute, New York, New York 10065, USA
:
Centro Superior de Investigación en Salud Pública - FISABIO, Valencia, Spain.
Centers of Biomedical Research Network (CIBER) in Epidemiology and Public Health, Madrid, Spain
Green Published
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