Highly Synergistic Effects of Melittin with Conventional Antibiotics Against Multidrug-Resistant Isolates of Acinetobacter baumannii and Pseudomonas aeruginosa

Background: Morbidity and mortality due to multidrug-resistant (MDR) bacteria are of great concern in burn patients. In this critical condition, synergism between antimicrobial peptides and conventional antibiotics would be a promising strategy. Accordingly, this study aimed to determine the therapeutic value of melittin as a natural peptide by examining its synergistic effect with conventional antibiotics against MDR isolates of Acinetobacter baumannii and Pseudomonas aeruginosa. Materials and Methods: Fifteen clinical isolates for each kind of bacteria were collected from burn patients. Antibiotic susceptibility of all isolates was evaluated by disk diffusion method. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration for melittin, colistin, doripenem, doxycycline, and ceftazidime were also examined. Fractional inhibitory concentration (FIC) of melittin in combination with the antibiotics was determined for six MDR isolates. The cytotoxicity of melittin in combination with the antibiotics was examined on a normal human cell line. Results: The geometric means of MIC (GM(MIC)) for melittin and doripenem after combination were reduced to 61.5- and 51.5-fold, respectively, against MDR A. baumannii isolates. These reductions for melittin-doripenem and melittin-ceftazidime against MDR P. aeruginosa isolates were (63.5 and 58)-fold and (16 and 11)-fold, respectively. FIC for melittin-doripenem against A. baumannii and FIC for melittin-doripenem and melittin-ceftazidime against P. aeruginosa strains were <= 0.5. This issue caused a decrease of up to 104-, 68-, and 17-fold, respectively, in the cytotoxicity of melittin. Conclusion: In conclusion, the synergism of melittin at its nontoxic dose with doripenem and ceftazidime could be of great therapeutic value as a topical drug against burn infections caused by MDR bacteria.