Association between use of different antibiotics and trimethoprim resistance: going beyond the obvious crude association

作者：Koen B. Pouwels, Rachel Freeman, Berit Müller‐Pebody, Graeme Rooney, Katherine L. Henderson, Julie V. Robotham, Timo Smieszek · 发表于：Journal of Antimicrobial Chemotherapy · 年份：2018 · DOI：10.1093/jac/dky031 · 被引用次数：96 · 研究领域：Antibiotic Use and Resistance、Antibiotic Resistance in Bacteria、Urinary Tract Infections Management

Objectives: To evaluate the association between use of different antibiotics and trimethoprim resistance at the population level. Methods: Monthly primary care prescribing data were obtained from NHS Digital. Positive Enterobacteriaceae records from urine samples from patients between April 2014 and January 2016 in England were extracted from PHE's Second Generation Surveillance System (SGSS). Elastic net regularization and generalized boosted regression models were used to evaluate associations between antibiotic prescribing and trimethoprim resistance, both measured at Clinical Commission Group level. Results: In total, 2 487 635 (99%) of 2 513 285 urine Enterobacteriaceae samples from 1 667 839 patients were tested for trimethoprim resistance. Using both elastic net regularization and generalized boosted regression models, geographical variation in trimethoprim resistance among Enterobacteriaceae urinary samples could be partly explained by geographical variation in use of trimethoprim (relative risk = 1.14, 95% CI = 1.02-1.75; relative influence = 4.1) and penicillins with extended spectrum (mainly amoxicillin/ampicillin in England) (relative risk = 1.19, 95% CI = 1.11-1.30; relative influence = 7.4). Nitrofurantoin use was associated with lower trimethoprim resistance levels (relative risk = 0.83, 95% CI = 0.57-0.96; relative influence = 9.2). Conclusions: Use of amoxicillin/ampicillin explained more of the variance in trimethoprim resistance than trimethoprim use, sugge...