Efficacy of Mastoparan-AF alone and in combination with clinically used antibiotics on nosocomial multidrug-resistant Acinetobacter baumannii

摘要

Emergence of multidrug-resistant Acinetobacter baumannii (MDRAB) has become a critical clinical problem worldwide and limited therapeutic options for infectious diseases caused by MDRAB. Therefore, there is an urgent need for the development of new antimicrobial agents or alternative therapy to combat MDRAB infection. The aim of this study was to investigate effects of Mastoparan-AF (MP-AF), an amphipathic peptide isolated from the hornet venom of Vespa affinis with broad-spectrum antimicrobial activity, on MDRAB. As compared with clinical used antibiotics, MP-AF exhibited potent antimicrobial activity at 2-16@mg/ml against the reference strain A. baumannii ATCC 15151 and seven MDRAB clinical isolates, especially the colistin-resistant MDRAB, E0158. The synergistic antimicrobial combination study revealed that MP-AF acted synergistically with specific antibiotics, e.g., ciprofloxacin, trimethoprim/sulfamethoxazole (SXT) or colistin against some isolates of the MDRAB. It was noteworthy when MP-AF combined with SXT exhibited synergistic activity against all SXT-resistant MDRAB isolates. The synergistic combination of MP-AF and antibiotics could reduce the dosage recommended of each antimicrobial agent and improve the safety of medications with ignorable adverse effects, such as colistin with nephrotoxicity in therapeutic dose. Furthermore, MP-AF combined with antibiotics with different antimicrobial mechanisms could reduce selective pressure of antibiotics on bacteria and prevent the emergence of antimicrobial-resistant strains. Importantly, we are the first finding that MP-AF could make MDRAB from the original non-susceptibility to SXT become sensitivity. In conclusion, MP-AF alone or in combination with other antibiotics, especially SXT, is a potential candidate against MDRAB infection in clinical medicine.