Insights into durability against resistance from the antibiotic nitrofurantoin

Abstract

Nitrofurantoin has shown exceptional durability against resistance over 70 years of use. This longevity stems from factors such as rapid achievement of therapeutic concentrations, multiple physiological targets against bacteria, low risk of horizontal gene transfer, and the need to acquire multiple mutations to achieve resistance. These combined features limit resistance emergence and spread of nitrofurantoin resistance. We propose nitrofurantoin as an exemplar for developing other durable treatments.

Keywords: Antimicrobial resistance; Drug regulation; Molecular evolution.

Fig. 1. Increased nitrofurantoin prescribing is not associated with increased nitrofurantoin resistance (twelve-month rolling averages, data from England, 2015—2023).

A Count of nitrofurantoin and trimethoprim prescriptions. B Resistance to nitrofurantoin and trimethoprim in E. coli and other coliforms isolated from urine. Vertical dashed lines in A and B indicate date of switch to nitrofurantoin as first-choice antibiotic. C Resistance and nitrofurantoin prescribing for each of the 42 healthcare regions in England (Integrated Care Boards, ICBs), averaged across the twelve-month period ending in December 2023 (grey areas denote 95% confidence interval for the linear regression; clipped symbols at the bottom of the plot denote ICBs with 0% recorded resistance). Data from the UK Office for Health Improvement and Disparities Fingertips data collection.