Worldwide antibiotic resistance dynamics: how different is it from one drug-bug pair to another?

Abstract

SummaryBackgroundAntibiotic resistance (ABR) is a major concern for global health. However, factors driving its emergence and dissemination are not fully understood. Identification of such factors is crucial to explain heterogeneity in ABR rates observed across space, time and species and antibiotics.MethodsWe analyzed count data of clinical isolates from 51 countries over 2006-2019 for thirteen drug-bug pairs from the ATLAS surveillance system. We characterized ABR spatial and temporal patterns and used a mixed-effect negative binomial model, accounting for country-year dependences with random effects (RE), to investigate associations with potential drivers including antibiotic sales, economic and health indicators, meteorological data, population density and tourism.FindingsABR patterns were strongly country and drug-bug pair dependent. In 2019, median ABR rates ranged from 6×3% (interquartile range (IQR): 19×7%) for carbapenem-resistant (CR)Klebsiella pneumoniaeto 80×7% (IQR: 41×8%) for fluoroquinolone-resistant (FR)Acinetobacter baumannii, with heterogeneity across countries. Over 2006-2019, carbapenem resistance was on the rise in >60% of investigated countries, while no global trend was observed for other resistances. Multivariable analyses identified significant associations of ABR with country-level selecting antibiotic sales, but only in FR-Escherichia coli, FR-Pseudomonas aeruginosaand CR-A. baumannii;with temperature in investigated Enterobacterales but not in other drug-bug pairs; and with the health system quality for all drug-bug pairs exceptEnterococciandStreptococcus pneumoniaepairs. Despite wide consideration of possible explanatory variables, drug-bug pairs ABR rates still showed unexplained spatial RE variance.InterpretationOur findings reflect the diversity of mechanisms driving global antibiotic resistance across pathogens and stress the need for tailored interventions to tackle bacterial resistance.FundingIndependent research Pfizer Global Medical Grant; ANR Labex IBEID (ANR-10-LABX-62)