Polymyxin B adjuvants against polymyxin B- and carbapenem-resistant Gram-negative bacteria
Polymyxin B (PMB) is one of the few therapeutic options for treating infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the emergence of PMB-resistant CR-GNB strains has prompted the exploration of antibiotic adjuvants as potential therapeutic avenues. Thus, this stu...
Saved in:
Published in | Future microbiology p. 1 |
---|---|
Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
11.09.2024
|
Subjects | |
Online Access | Get more information |
Cover
Loading…
Summary: | Polymyxin B (PMB) is one of the few therapeutic options for treating infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the emergence of PMB-resistant CR-GNB strains has prompted the exploration of antibiotic adjuvants as potential therapeutic avenues. Thus, this study evaluates the potential of 3,5-dinitrobenzoic acid derivatives (DNH01, DNH11, DNH13 and DNH20) and isoniazid-
-acylhydrazones (INZ1-7, INZ9 and INZ11) as adjuvants to enhance PMB efficacy against CR-GNB.
MIC, MBC and drug combination assays were conducted using multidrug-resistant clinical isolates of
and
. In addition, the effects of PMB and PMB + DNH derivatives were assessed through flow cytometry and scanning electron microscopy (SEM).
DNH01, DNH11 and DNH20, unlike the INH-acylhydrazones, significantly restored PMB activity (MIC ≤ 2 μg/ml) in 80% of the tested isolates. Flow cytometry and SEM assays confirmed that DNH derivatives rescued the activity of PMB, yielding results comparable to those expected for PMB alone but at 256-fold lower concentrations.
These findings suggest DNH derivatives hold substantial promise as PMB adjuvants to combat PMB-resistant CR-GNB infections. |
---|---|
ISSN: | 1746-0921 |
DOI: | 10.1080/17460913.2024.2398312 |