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

• Published in: Future microbiology p. 1
• Main Authors: Salvaterra Pasquini, João Paulo, Queiroz, Paula Assis, Rodrigues do Amaral, Pedro Henrique, da Silva, Thalita Camilo, Souza Bonfim Mendonça, Patricia de, Vandresen, Fábio, Carvalho Ceolis, João Pedro, de Lima Scodro, Regiane Bertin, Caleffi-Ferracioli, Katiany Rizzieri, Cardoso, Rosilene Fressatti, Dias Siqueira, Vera Lúcia
• Format: Journal Article
• Language: English
• Published: England 11.09.2024
• Subjects: isoniazid-acylhydrazones derivatives; 3,5-dinitrobenzoylhydrazonic derivatives; polymyxin; bacterial resistance; enterobacterales
• ISSN: 1746-0921
• DOI: 10.1080/17460913.2024.2398312

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.