melitten and Pseudomonas-Infections

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.. 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.. The geometric means of MIC (GM. 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.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Burns; Ceftazidime; Cell Line; Cell Survival; Doripenem; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Melitten; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Synthetic peptides, ranging from 12 to 18 residues, containing partial sequences from natural cecropin A and melittin were tested for activity in an experimental pseudomonas keratitis model in rabbits. In separate experiments, two Pseudomonas aeruginosa strains: (a) a clinical isolated strain, and (b) an American Type Culture Collection (ATCC) strain, were inoculated into the stroma of one cornea of each rabbit. Peptides were topically applied at 0.1% in phosphate-buffered saline (PBS) and compared with PBS alone and 0.3% gentamicin eye drops. Clinical evaluation, based on the McDonald-Shadduck scale, was performed during a > 48-h period after the bacterial inoculation. The peptide-treated animals showed significantly lower (p < 0.05) inflammatory signs and lower anterior-segment bacterial damage compared with PBS-treated animals, after the first 6 h. The antiinflammatory/antimicrobial activity was non significantly differnt (p > 0.05) from that in animals treated with gentamicin. We conclude that peptides keeping the sequence KWKLFKK from cecropin A and at least the sequence VLKVL from melittin show promise as novel agents in topical ocular therapy of bacterial keratitis.

Topics: Administration, Topical; Animals; Anti-Infective Agents; Antimicrobial Cationic Peptides; Chromatography, High Pressure Liquid; Cornea; Corneal Ulcer; Disease Models, Animal; Eye Infections, Bacterial; Male; Melitten; Ophthalmic Solutions; Peptide Fragments; Peptides; Pseudomonas Infections; Rabbits; Random Allocation