In vivo bactericidal effect of colistin\u2013linezolid combination in a murine model of MDR and XDR Acinetobacter baumannii pneumonia

Xiao-Lin Ma,Yong-Zhong Guo,Yan-Min Wu,Zhen Huang,Jie Sun,Wei-Tao Gong

doi:10.1038/s41598-020-74503-0

Xiao-Lin Ma, Yong-Zhong Guo + Show 4 more

Open Access

https://doi.org/10.1038/s41598-020-74503-0

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Abstract

Recently, paradoxical combinations of colistin with anti-Gram-positive bacterial agents were introduced as a treatment alternative for multidrug-resistant Acinetobacter baumannii (MDRAB) infection. We assessed the therapeutic efficacy of the colistin–linezolid combination regimen in vitro and in a murine model of Acinetobacter baumannii pneumonia. A multidrug-resistant clinical strain (MDRAB31) and an extensively drug-resistant clinical strain (XDRAB78) were used in this study. The survival rates of mice and bacterial counts in lung tissue were used to assess the effects of colistin–linezolid combination. The survival rates of colistin–linezolid combination groups significantly increased compared with colistin groups for MDRAB31 (72% versus 32%, P = 0.03) and for XDRAB78 (92% versus 68%, P = 0.031). The colistin–linezolid combination groups significantly reduced the bacterial counts in lung tissue compared with colistin groups for MDRAB31 and for XDRAB78 (P < 0.05). The colistin–linezolid combination had a bactericidal and synergistic effect compared with colistin alone in time-kill assay and in murine model of pneumonia. Our data demonstrated the synergistic effect of colistin–linezolid combination regimen as a treatment alternative for the severe pulmonary infection caused by MDRAB and XDRAB.

Highlights

Acinetobacter baumannii (A. baumannii) has become an important cause of hospital-associated infections affecting critically ill patients all over the world over the last decades[1], and is mainly responsible for hospital-associated and ventilator-associated p neumonia[2]
Both strains of A. baumannii resulted susceptible to colistin and showed high values to linezolid
The colistin–linezolid combination resulted in synergy for MDRAB31, additivity/indifference for XDRAB78

Summary

Introduction

Acinetobacter baumannii (A. baumannii) has become an important cause of hospital-associated infections affecting critically ill patients all over the world over the last decades[1], and is mainly responsible for hospital-associated and ventilator-associated p neumonia[2]. Colistin-based combination therapies of existing drugs, including paradoxical combinations of colistin with anti-Gram-positive bacterial agents, have been made exploration and research to combat MDR A. baumannii infection[6,7,8,9,10,11]. Since linezolid natural resistance to Gram-negative bacteria is due to the inability of drug to achieve effective intracytoplasmic concentrations, colistin can be used to increase the accumulation of linezolid by disrupting the permeability barrier of outer membrane and by inhibiting bacterial efflux pumps a ctivities[12]. Little in vivo data exists concerning the effectiveness of colistin with linezolid for the treatment of A. baumannii infection. Since linezolid has been approved mainly for the hospital-acquired pneumonia treatment, our objective was to investigate the efficacy of the combination of colistin with linezolid in a murine model of A. baumannii pneumonia

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