Synergistic Peptide-Antibiotic Approach to Combat Multidrug-Resistant Acinetobacter baumannii

Abstract

Background: Antibacterial peptides have a broad antibacterial spectrum and are not affected by classical resistance mechanisms; therefore, they can be used in combination with classic antibiotics to treat multidrug-resistant Acinetobacter baumannii infections, making them an alternative for the development of new therapeutic strategies. Objectives: This study aimed to assess the effectiveness of combining amphiphilic peptides, specifically C12-prp and mastoparan, with antibiotics in combating A. baumannii clinical isolates. Methods: We investigated combinations that inhibited the growth of A. baumannii clinical isolates, consisting of 24 extensively drug-resistant (XDR) and 11 pan-drug-resistant (PDR) strains collected between January 2004 and December 2014 at Chosun University Hospital using a multiple combination bactericidal test (MCBT). A time-kill study was used to confirm the bactericidal activity and synergism of the four combinations selected via MCBT. Results: Four combinations (C12-prp-colistin, C12-prp-rifampicin, mastoparan-colistin, and mastoparan-rifampicin) showed 100% (24/24) synergy with XDR A. baumannii strains. However, in the case of the PDR strains, only two combinations, C12-prp-colistin and mastoparan-colistin, showed a 9.1% (1/11) synergy. Moreover, the mastoparan-colistin and mastoparan-rifampicin combinations showed 100% (24/24) bactericidal activity against the XDR A. baumannii strains, whereas the C12-prp-colistin and C12-prp-rifampicin combinations showed 91.7% (22/24) bactericidal activity. None of the combinations showed bactericidal activity against PDR strains. Conclusions: Our study highlighted the substantial synergistic antibacterial efficacy of C12-prp and mastoparan peptides when combined with colistin or rifampicin. Furthermore, this approach could be a promising alternative for developing new treatment strategies for XDR A. baumannii infections.