Analysis of the seasonal relationship between antibiotic use and resistance

Abstract

Antibiotic resistance is a growing public health concern that threatens our ability to treat infectious diseases caused by bacterial pathogens. Antibiotic use is a major driver of resistance, and understanding how the relationship between use and resistance varies between diverse pathogens and antibiotics is important for informing broadly effective intervention strategies to combat antibiotic resistance. Here, we leveraged existing seasonal fluctuations in antibiotic use in Boston, MA as a framework for characterizing the relationship between antibiotic use and resistance. In Chapter 2, we measured the association between seasonal antibiotic use and resistance for 5 antibiotic classes in 3 clinically important pathogens, Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae. We found that this association varied widely across the species-antibiotic combinations, with seasonal resistance across all antibiotics peaking in the winter despite varied seasonal patterns in their use. In Chapter 3, we followed up on these findings by examining the contribution of two additional factors – indirect selection by winter-peaking penicillin and macrolide use given the context of multi-drug resistance and seasonally varied sampling of isolates from demographic groups with different rates of resistance – to explaining the observed seasonal use-resistance relationships across pathogens and antibiotics. We found that both factors contributed to but did not fully explain the observed seasonal patterns of resistance. Together, these findings provide useful insights into the complexity of the antibiotic use-resistance relationship and lay the groundwork for future analyses to further understand the factors that impact this relationship.