Quantifying antibiotic impact on within-patient dynamics of extended-spectrum beta-lactamase resistance

Abstract

Antibiotic-induced perturbation of the human gut flora is expected to play an important role in mediating the relationship between antibiotic use and the population prevalence of antibiotic resistance in bacteria, but little is known about how antibiotics affect within-host resistance dynamics. Here we develop a data-driven model of the within-host dynamics of extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. We use blaCTX-M (the most widespread ESBL gene family) and 16S rRNA (a proxy for bacterial load) abundance data from 833 rectal swabs from 133 ESBL-positive patients followed up in a prospective cohort study in three European hospitals. We find that cefuroxime and ceftriaxone are associated with increased blaCTX-M abundance during treatment (21% and 10% daily increase, respectively), while treatment with meropenem, piperacillin-tazobactam, and oral ciprofloxacin is associated with decreased blaCTX-M (8% daily decrease for all). The model predicts that typical antibiotic exposures can have substantial long-term effects on blaCTX-M carriage duration.

Estimating epidemiologic dynamics from cross-sectional viral load distributions

“…One unexplained observation which has been consistently observed in many locations is that the distribution of observed Ct values has decreased over the course of the current SARS-CoV-2 pandemic, which has led to questions over whether the virus has lost some amount of fitness (15,16,18). Different swab types, sample types, or instruments may alter the variability in the Ct distribution (41,42), leading to different relationships between the specific Ct distribution and the epidemic trajectory. Setting-specific calibrations, for example based on a reference range of Ct values, will be useful to ensure accuracy.…”

“…These results are sensitive to the true distribution of observed viral loads each day after infection. Different swab types, sample types, or instruments may alter the variability in the Ct distribution ( 41,42 ), leading to different relationships between the specific Ct distribution and the epidemic trajectory. Setting-specific calibrations, for example based on a reference range of Ct values, will be useful to ensure accuracy.…”

Gut microbiome dysbiosis during COVID-19 is associated with increased risk for bacteremia and microbial translocation.

“…The lower diversity associated with samples from patients with BSIs led us to investigate their bacterial taxon compositions and the potential that gut dysbiosis was associated with BSI events. All BSI patients had received antibiotic treatments during hospitalization, which could exacerbate COVID-19 induced shifts in microbiota populations 11,12,15 , but may indeed be administered in response to a suspected or confirmed BSI. However, we noted that most BSI patients (80%) also received antibiotics prior to their BSI.…”

Metapopulation ecology links antibiotic resistance, consumption, and patient transfers in a network of hospital wards

“…Current rankings of antibiotics for de-escalation and sparing strategies rely on expert consensus with partial agreement ( Weiss et al, 2015 ), themselves based on conflicting evidence ( Acar, 1997 ; Huttner et al, 2016 ). This is further complicated by the fact that the association between antibiotic use and resistance is not uniform across pathogen species ( Bell et al, 2014 ) or classes of antibiotics ( Niehus et al, 2020 ). Moreover, antibiotic consumption can also have long-term effects on the carriage of resistant bacteria within patients ( Niehus et al, 2020 ).…”

“…This is further complicated by the fact that the association between antibiotic use and resistance is not uniform across pathogen species ( Bell et al, 2014 ) or classes of antibiotics ( Niehus et al, 2020 ). Moreover, antibiotic consumption can also have long-term effects on the carriage of resistant bacteria within patients ( Niehus et al, 2020 ).…”