Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, United States of America.
PLoS Biol. 2022 Mar 9;20(3):e3001579. doi: 10.1371/journal.pbio.3001579. eCollection 2022 Mar.
Understanding how antibiotic use drives resistance is crucial for guiding effective strategies to limit the spread of resistance, but the use-resistance relationship across pathogens and antibiotics remains unclear. We applied sinusoidal models to evaluate the seasonal use-resistance relationship across 3 species (Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae) and 5 antibiotic classes (penicillins, macrolides, quinolones, tetracyclines, and nitrofurans) in Boston, Massachusetts. Outpatient use of all 5 classes and resistance in inpatient and outpatient isolates in 9 of 15 species-antibiotic combinations showed statistically significant amplitudes of seasonality (false discovery rate (FDR) < 0.05). While seasonal peaks in use varied by class, resistance in all 9 species-antibiotic combinations peaked in the winter and spring. The correlations between seasonal use and resistance thus varied widely, with resistance to all antibiotic classes being most positively correlated with use of the winter peaking classes (penicillins and macrolides). These findings challenge the simple model of antibiotic use independently selecting for resistance and suggest that stewardship strategies will not be equally effective across all species and antibiotics. Rather, seasonal selection for resistance across multiple antibiotic classes may be dominated by use of the most highly prescribed antibiotic classes, penicillins and macrolides.
了解抗生素的使用如何推动耐药性的产生对于指导有效策略来限制耐药性的传播至关重要，但病原体和抗生素之间的使用-耐药性关系仍不清楚。我们应用正弦模型评估了马萨诸塞州波士顿市 3 种（金黄色葡萄球菌、大肠埃希菌和肺炎克雷伯菌）和 5 种抗生素类别（青霉素类、大环内酯类、喹诺酮类、四环素类和硝基呋喃类）的季节性使用-耐药性关系。在 15 种 9 种物种-抗生素组合的住院和门诊分离物中，所有 5 种类别的门诊使用以及耐药性均显示出统计学上显著的季节性幅度（错误发现率（FDR）<0.05）。虽然各类别使用的季节性高峰不同，但所有 9 种物种-抗生素组合的耐药性在冬季和春季达到高峰。因此，季节性使用与耐药性之间的相关性差异很大，所有抗生素类别的耐药性与冬季高峰类别的使用（青霉素类和大环内酯类）最正相关。这些发现挑战了抗生素使用独立选择耐药性的简单模型，并表明管理策略在所有物种和抗生素中不会具有同等效果。相反，多种抗生素类别对耐药性的季节性选择可能主要由最广泛使用的抗生素类别，青霉素类和大环内酯类的使用决定。
