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

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

doi:10.3389/fcimb.2020.608547

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

Front Cell Infect Microbiol. 2020 Dec 21:10:608547. doi: 10.3389/fcimb.2020.608547. eCollection 2020.

Authors

Zi-Xing Zhong^{1

2}, Ze-Hua Cui^{1

2}, Xiao-Jie Li³, Tian Tang^{1

2}, Zi-Jian Zheng^{1

2}, Wei-Na Ni^{1

2}, Liang-Xing Fang^{1

2}, Yu-Feng Zhou^{1

2}, Yang Yu^{1

2}, Ya-Hong Liu^{1

2

4}, Xiao-Ping Liao^{1

2

4}, Jian Sun^{1

2

4}

Affiliations

¹ National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, China.
² Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, China.
³ Department of Laboratory Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
⁴ Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China.

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.

Keywords: G. mellonella model; MDR UPEC; amikacin; antibiotic combination; nitrofurantoin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amikacin / pharmacology
Anti-Bacterial Agents / pharmacology
Anti-Bacterial Agents / therapeutic use
Escherichia coli Infections* / drug therapy
Humans
Nitrofurantoin / pharmacology
Urinary Tract Infections* / drug therapy
Uropathogenic Escherichia coli*

Substances

Anti-Bacterial Agents
Amikacin
Nitrofurantoin