Genomic insights into nitrofurantoin resistance mechanisms and epidemiology in clinical Enterobacteriaceae

Abstract

Aim: Multidrug-resistant enterobacteria are highly associated with invasive devices and intensive care units. Increasing resistance to carbapenems is leading to the use of older and neglected antibiotics such as nitrofurantoin (NFT). The genomics of NFT resistance was investigated. Results & conclusion: High-level resistance to NFT (minimum inhibitory concentration ≥128-512 mg/l) was recorded in 31/36 isolates (89.6%), many of which were from intensive care units (n = 20), urine (n = 17) or invasive procedures (n = 10). Efflux pump inhibitors had little effect on NFT's minimum inhibitory concentrations albeit oqxAB was prevalent in most isolates (n = 32). Various species- and clone-specific mutations mediating high-level NFT resistance were detected in nfsA, nfsB and ribE proteins through comparative genomics. Global phylogenomics showed local and independent emergence of NFT resistance in Enterobacteriaceae. NFT stewardship is advised.