Polymyxin B adjuvants against polymyxin B- and carbapenem-resistant Gram-negative bacteria.

Future microbiology 2024

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Aim: 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-N-acylhydrazones (INZ1-7, INZ9 and INZ11) as adjuvants to enhance PMB efficacy against CR-GNB.Materials & methods: MIC, MBC and drug combination assays were conducted using multidrug-resistant clinical isolates of Enterobacterales and Acinetobacter baumannii. In addition, the effects of PMB and PMB + DNH derivatives were assessed through flow cytometry and scanning electron microscopy (SEM).Results: 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.Conclusion: These findings suggest DNH derivatives hold substantial promise as PMB adjuvants to combat PMB-resistant CR-GNB infections.

Citation

João Paulo Salvaterra Pasquini, Paula Assis Queiroz, Pedro Henrique Rodrigues do Amaral, Thalita Camilo da Silva, Patricia de Souza Bonfim Mendonça, Fábio Vandresen, João Pedro Carvalho Ceolis, Regiane Bertin de Lima Scodro, Katiany Rizzieri Caleffi-Ferracioli, Rosilene Fressatti Cardoso, Vera Lúcia Dias Siqueira. Polymyxin B adjuvants against polymyxin B- and carbapenem-resistant Gram-negative bacteria. Future microbiology. 2024;19(17):1445-1454