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

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) we...

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Autores principales: Wang, J., Stegger, M., Moodley, Arshnee, Yang, M.
Formato: Journal Article
Lenguaje:Inglés
Publicado: MDPI 2023
Materias:
Acceso en línea:https://hdl.handle.net/10568/129079
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author Wang, J.
Stegger, M.
Moodley, Arshnee
Yang, M.
author_browse Moodley, Arshnee
Stegger, M.
Wang, J.
Yang, M.
author_facet Wang, J.
Stegger, M.
Moodley, Arshnee
Yang, M.
author_sort Wang, J.
collection Repository of Agricultural Research Outputs (CGSpace)
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.
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spelling CGSpace1290792025-12-08T10:29:22Z Drug combination of ciprofloxacin and polymyxin B for the treatment of multidrug-resistant Acinetobacter baumannii infections: A drug pair limiting the development of resistance Wang, J. Stegger, M. Moodley, Arshnee Yang, M. antimicrobial resistance 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. 2023-02-21 2023-02-28T08:48:27Z 2023-02-28T08:48:27Z Journal Article https://hdl.handle.net/10568/129079 en Open Access MDPI 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.
spellingShingle antimicrobial resistance
Wang, J.
Stegger, M.
Moodley, Arshnee
Yang, M.
Drug combination of ciprofloxacin and polymyxin B for the treatment of multidrug-resistant Acinetobacter baumannii infections: A drug pair limiting the development of resistance
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
title_full Drug combination of ciprofloxacin and polymyxin B for the treatment of multidrug-resistant Acinetobacter baumannii infections: A drug pair limiting the development of resistance
title_fullStr Drug combination of ciprofloxacin and polymyxin B for the treatment of multidrug-resistant Acinetobacter baumannii infections: A drug pair limiting the development of resistance
title_full_unstemmed Drug combination of ciprofloxacin and polymyxin B for the treatment of multidrug-resistant Acinetobacter baumannii infections: A drug pair limiting the development of resistance
title_short Drug combination of ciprofloxacin and polymyxin B for the treatment of multidrug-resistant Acinetobacter baumannii infections: A drug pair limiting the development of resistance
title_sort drug combination of ciprofloxacin and polymyxin b for the treatment of multidrug resistant acinetobacter baumannii infections a drug pair limiting the development of resistance
topic antimicrobial resistance
url https://hdl.handle.net/10568/129079
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