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

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 Enterobacteriaceae species that acquired nonsusceptibility 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 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.

Lactobacillus supports Clostridiales to restrict gut colonization by multidrug-resistant Enterobacteriaceae

“…Therefore, ALP represent an optimal population to study how changes in the microbiota influence MRE intestinal colonization in humans. We reported that 60% of ALP from our cohort harbor detectable levels of MRE 17 . Moreover, we found that fecal MRE levels change considerably between different patients and within the same patient over time 17 .…”

“…We reported that 60% of ALP from our cohort harbor detectable levels of MRE 17 . Moreover, we found that fecal MRE levels change considerably between different patients and within the same patient over time 17 . An example of these changes is reflected in Fig.…”

“…We previously collected weekly fecal samples ( N = 802) from hospitalized acute leukemia patients (ALP; N = 133) to identify clinical variables associated with week-to-week changes in the levels of MRE 17 . ALP often receive antibiotics that potentially disrupt their microbiota and lead to frequent colonization by MRE.…”

“…admission type, comorbidities, etc.) 17 . Here, we aim to identify changes in the microbiome associated with MRE intestinal colonization levels, which could allow us to identify commensal bacteria that are key to confer resistance to these multidrug-resistant pathogens in humans.…”

“… a For each patient we collected clinical data (e.g. antibiotic treatment, type of hospital admission) as described in our previous publication 17 . Fecal samples were collected every week.…”