Colistin Combined With Tigecycline: A Promising Alternative Strategy to Combat Escherichia coli Harboring bla NDM- 5 and mcr-1

• Published in: Frontiers in microbiology 2019, Vol.10, p.2957-2957
• Main Authors: Zhou, Yu-Feng, Liu, Ping, Zhang, Chuan-Jian, Liao, Xiao-Ping, Sun, Jian, Liu, Ya-Hong
• Format: Article
• Language: English
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2019.02957

Infections due to carbapenem-resistant NDM-producing represent a major therapeutic challenge, especially in situations of pre-existing colistin resistance. The aim of this study was to investigate combinatorial pharmacodynamics of colistin and tigecycline against harboring and , with possible mechanisms explored as well. Colistin disrupted the bacterial outer-membrane and facilitated tigecycline uptake largely independent of expression, which allowed a potentiation of the tigecycline-colistin combination. A concentration-dependent decrease in colistin MIC and EC was observed with increasing tigecycline levels. Clinically relevant concentrations of colistin and tigecycline combination significantly decreased bacterial density of colistin-resistant by 3.9 to 6.1-log cfu/mL over 48 h at both inoculums of 10 and 10 cfu/mL, and were more active than each drug alone ( < 0.01). Importantly, colistin and tigecycline combination therapy was efficacious in the murine thigh infection model at clinically relevant doses, resulting in >2.0-log cfu/thigh reduction in bacterial density compared to each monotherapy. These data suggest that the use of colistin and tigecycline combination can provide a therapeutic alternative for infection caused by multidrug-resistant that harbored both and .