Antibiotic 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. Methods We analyzed count data of resistant isolates from 51 countries over 2006-2019 for nine drug-bug pairs from the surveillance database ATLAS. We characterized ABR spatial and temporal patterns and used a

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... d-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. Findings ABR patterns were strongly country and drug-bug pair dependent. In 2019, median ABR rates ranged from 6,3% for carbapenem-resistant (CR) Klebsiella pneumoniae to 72,3% for CR-Acinetobacter baumannii, with heterogeneity across countries (up to 50,2% of interquartile range for CR-A. baumannii). Over 2006-2019, carbapenem resistance was on the rise in >75% of investigated countries but no global trend was observed for other resistances. Multivariable analyses identified significant associations of ABR with antibiotic sales, but only in fluoroquinolone-resistant Escherichia coli, CR-A. baumannii and penicillin-resistant Streptococcus pneumoniae; with temperature in investigated Enterobacterales but not in other drug-bug pairs; and with the health system quality for most drug-bug pairs, except in Enterococci and S. pneumoniae. Despite wide consideration of possible explanatory variables, drug-bug pairs still showed high spatial RE variance. Interpretation These results reflect the diversity found among human bacterial pathogens and stress the difficulty to generalize global antibiotic resistance findings.