Antiparasitic nitazoxanide potentiates colistin against colistin-resistant Acinetobacter baumannii and Escherichia coli in vitro and in vivo

Mengxin Xu; Zhuocheng Yao; Jingchun Kong; Miran Tang; Qi Liu; Xiaotuan Zhang; Shiyi Shi; Xiangkuo Zheng; Jianming Cao; Tieli Zhou; Zhongyong Wang

doi:10.1128/spectrum.02295-23

Microbiology Spectrum (Jan 2024)

Antiparasitic nitazoxanide potentiates colistin against colistin-resistant Acinetobacter baumannii and Escherichia coli in vitro and in vivo

Mengxin Xu,
Zhuocheng Yao,
Jingchun Kong,
Miran Tang,
Qi Liu,
Xiaotuan Zhang,
Shiyi Shi,
Xiangkuo Zheng,
Jianming Cao,
Tieli Zhou,
Zhongyong Wang

Affiliations

Mengxin Xu: Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province , Wenzhou, China
Zhuocheng Yao: Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province , Wenzhou, China
Jingchun Kong: Department of Medical Lab Science, School of Laboratory Medicine and Life Science, Wenzhou Medical University , Wenzhou, China
Miran Tang: Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province , Wenzhou, China
Qi Liu: Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province , Wenzhou, China
Xiaotuan Zhang: Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province , Wenzhou, China
Shiyi Shi: Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province , Wenzhou, China
Xiangkuo Zheng: Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province , Wenzhou, China
Jianming Cao: Department of Medical Lab Science, School of Laboratory Medicine and Life Science, Wenzhou Medical University , Wenzhou, China
Tieli Zhou: Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province , Wenzhou, China
Zhongyong Wang: Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province , Wenzhou, China

DOI: https://doi.org/10.1128/spectrum.02295-23
Journal volume & issue: Vol. 12, no. 1

Abstract

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ABSTRACT Multidrug-resistant Gram-negative bacterial infections pose a serious threat to public health and safety. Colistin is a line of defense against these infections, but colistin-resistant (COL-R) bacteria have emerged worldwide. This study aimed to explore the synergistic potential of nitazoxanide (NTZ) in combination with colistin for the treatment of COL-R Acinetobacter baumannii and Escherichia coli strains in vitro and in vivo. The checkerboard and time-killing assays indicated that NTZ in combination with colistin exhibited potent antibacterial activity against COL-R A. baumannii and COL-R E. coli. The antibiofilm activity measured by crystal violet staining and scanning electron microscopy combined with a confocal laser scanning microscope revealed that the combination of NTZ and colistin could inhibit biofilm formation and eradicate the formed biofilm. This study also demonstrated that the application of this drug combination to an in vivo infection model significantly increased the survival rate of Galleria mellonella larvae. Hemolysis tests revealed that the combination of NTZ and colistin showed no cytotoxicity. Altogether, the combination of NTZ and colistin showed promising synergistic antibacterial and antibiofilm effects in vitro and in vivo. This combination might be used as an alternative therapy for treating COL-R A. baumannii and COL-R E. coli infections. IMPORTANCE Colistin is used as a last resort in many infections caused by multidrug-resistant Gram-negative bacteria; however, colistin-resistant (COL-R) is on the rise. Hence, it is critical to develop new antimicrobial strategies to overcome COL-R. We found that nitazoxanide (NTZ) combined with colistin showed notable synergetic antibacterial activity. These findings suggest that the NTZ/colistin combination may provide an effective alternative route to combat COL-R A. baumannii and COL-R Escherichia coli infections.

Published in Microbiology Spectrum

ISSN: 2165-0497 (Online)
Publisher: American Society for Microbiology
Country of publisher: United States
LCC subjects: Science: Microbiology
Website: https://journals.asm.org/journal/spectrum

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