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Published on: April 18, 2019
Contezolid and polymyxin B nonapeptide combination reveals antibacterial synergy against multidrug-resistant
Danrui Hao1, Yuhang Huang1, Tianzhu Zhao2
1Antibiotics Innovation and Resistance Control Key Laboratory of Sichuan Province, School of Pharmacy, Chengdu University, Chengdu, 610106, China.
Background:
Acinetobacter baumannii is a notorious clinical pathogen that predominantly causes nosocomial infections. The multidrug resistant Acinetobacter baumannii clinical isolates are becoming more prevalent on a global scale. In this study, we aimed to determine the potential synergistic antibacterial activity of contezolid in combination with polymyxin B nonapeptide (PBNP) against various A. baumannii strains.
Results:
Contezolid, a commonly-used agents targeting Gram-positive bacteria, in combination with PBNP (CP) was used to explore the potential synergistic antibacterial activity against A. baumannii in vitro and Caenorhabditis elegans models. We found that CP treatment exhibited a strong synergistic effect on A. baumannii or multidrug resistant A. baumannii. CP also inhibited the biofilm formation and alter morphology of A. baumannii compared to the control group. Moreover, the residual bacteria were significantly decreased in the CP-treated murine alveolar macrophages (MH-S). Importantly, CP treatment improved the survival of C. elegans compared to the control or monotherapy group.
Conclusions:
This strategy improved antibacterial activity spectrum of agents targeting Gram-positive bacteria like contezolid. Nevertheless, CP combination therapy requires further validation in mammalian infection models.
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