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Drug combination of ciprofloxacin and polymyxin B for the treatment of multidrug-resistant Acinetobacter baumannii infections: A drug pair limiting the development of resistance

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Title Drug combination of ciprofloxacin and polymyxin B for the treatment of multidrug-resistant Acinetobacter baumannii infections: A drug pair limiting the development of resistance
 
Creator Wang, J.
Stegger, M.
Moodley, Arshnee
Yang, M.
 
Subject antimicrobial resistance
 
Description Polymyxins are considered as last–resort antibiotics to treat infections caused by Acinetobacter baumannii. However, there are increasing reports of resistance in A. baumannii to polymyxins. In this study, inhalable combinational dry powders consisting of ciprofloxacin (CIP) and polymyxin B (PMB) were prepared by spray–drying. The obtained powders were characterized with respect to the particle properties, solid state, in vitro dissolution and in vitro aerosol performance. The antibacterial effect of the combination dry powders against multidrug–resistant A. baumannii was assessed in a time–kill study. Mutants from the time–kill study were further investigated by population analysis profiling, minimum inhibitory concentration testing, and genomic comparisons. Inhalable dry powders consisting of CIP, PMB and their combination showed a fine particle fraction above 30%, an index of robust aerosol performance of inhaled dry powder formulations in the literature. The combination of CIP and PMB exhibited a synergistic antibacterial effect against A. baumannii and suppressed the development of CIP and PMB resistance. Genome analyses revealed only a few genetic differences of 3–6 SNPs between mutants and the progenitor isolate. This study suggests that inhalable spray–dried powders composed of the combination of CIP and PMB is promising for the treatment of respiratory infections caused by A. baumannii, and this combination can enhance the killing efficiency and suppress the development of drug resistance.
 
Date 2023-02-21
2023-02-28T08:48:27Z
2023-02-28T08:48:27Z
 
Type Journal Article
 
Identifier Wang, J., Stegger, M., Moodley, A. and Yang, M. 2023. Drug combination of ciprofloxacin and polymyxin B for the treatment of multidrug-resistant Acinetobacter baumannii infections: A drug pair limiting the development of resistance. Pharmaceutics 15(3): 720.
1999-4923
https://hdl.handle.net/10568/129079
https://doi.org/10.3390/pharmaceutics15030720
 
Language en
 
Rights CC-BY-4.0
Open Access
 
Format 720
 
Publisher MDPI
 
Source Pharmaceutics