Nitrofurantoin Combined With Amikacin: A Promising Alternative Strategy for Combating MDR Uropathogenic Escherichia coli.

Zi-Xing Zhong,Wei-Na Ni,Liang-Xing Fang,Xiao-Ping Liao,Ze-Hua Cui,Zi-Jian Zheng,Jian Sun,Xiao-Jie Li,Ya-Hong Liu,Yu-Feng Zhou,Tian Tang,Yang Yu

doi:10.3389/fcimb.2020.608547

Abstract

Urinary tract infections (UTI) are common infections that can be mild to life threatening. However, increased bacterial resistance and poor patient compliance rates have limited the effectiveness of conventional antibiotic therapies. Here, we investigated the relationship between nitrofurantoin and amikacin against 12 clinical MDR uropathogenic Escherichia coli (UPEC) strains both in vitro and in an experimental Galleria mellonella model. In vitro synergistic effects were observed in all 12 test strains by standard checkerboard and time-kill assays. Importantly, amikacin or nitrofurantoin at half of the clinical doses were not effective in the treatment of UPEC infections in the G. mellonella model but the combination therapy significantly increased G. mellonella survival from infections caused by all 12 study UPEC strains. Taken together, these results demonstrated synergy effects between nitrofurantoin and amikacin against MDR UPEC.

Highlights

Urinary tract infections (UTI) are defined microbiologically as the inflammatory response of the urothelial to microbial pathogens and are some of the most common bacterial infections affecting 150 million people each year worldwide (Klein and Hultgren, 2020)
UTIs are most commonly associated with uropathogenic Escherichia coli (UPEC) and E. coli ST131 is the globally dominant multiple drug-resistant (MDR) UPEC clone that causes infections associated with limited treatment options (Daoud et al, 2015; Phan et al, 2020)
These data indicated that combination of amikacin and nitrofurantoin can synergize to combat MDR UPEC strains

Summary

Introduction

Urinary tract infections (UTI) are defined microbiologically as the inflammatory response of the urothelial to microbial pathogens and are some of the most common bacterial infections affecting 150 million people each year worldwide (Klein and Hultgren, 2020). UTIs are most commonly associated with uropathogenic Escherichia coli (UPEC) and E. coli ST131 is the globally dominant multiple drug-resistant (MDR) UPEC clone that causes infections associated with limited treatment options (Daoud et al, 2015; Phan et al, 2020). These infections can be highly recurrent and following antibiotic therapy, 20–30% of women with acute UTIs will have a recurrent episode within six months and half of these recurrences are caused by the same UPEC strain that caused the initial infection (Godaly et al, 2015). Carbapenems have been recommended for treating UTIs caused by extended spectrum b-lactamase (ESBL) producing bacteria but currently are being restricted due to increased resistance (Han et al, 2015). Its potential ototoxicity and nephrotoxicity is dose related so that it could be efficacious and safe for the treatment of pyelonephritis and sepsis if managed properly (Leibovici et al, 2009)

Methods

Results

Conclusion