51. Enhanced Efficacy of Combinations of Pexiganan with Colistin Versus Acinetobacter Baumannii in Experimental Sepsis
- Author
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Andrea Giacometti, Daniele Minardi, Oriana Simonetti, Maria Pelloni, Annamaria Offidani, Mario Guerrieri, Maria Michela Cappelletti Trombettoni, Oscar Cirioni, Elisa Pierpaoli, Mauro Provinciali, Roberto Ghiselli, Fiorenza Orlando, and Alessandra Barucca
- Subjects
Acinetobacter baumannii ,Male ,0301 basic medicine ,medicine.medical_treatment ,030106 microbiology ,Pharmacology ,Critical Care and Intensive Care Medicine ,Bacterial counts ,Immunophenotyping ,Sepsis ,Mice ,03 medical and health sciences ,In vivo ,polycyclic compounds ,medicine ,Animals ,Saline ,Mice, Inbred BALB C ,biology ,Colistin ,business.industry ,Positive interaction ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,biology.organism_classification ,medicine.disease ,Anti-Bacterial Agents ,030104 developmental biology ,Emergency Medicine ,bacteria ,lipids (amino acids, peptides, and proteins) ,business ,Bacteria ,Antimicrobial Cationic Peptides ,medicine.drug - Abstract
We investigated the efficacy of colistin combined with pexiganan in experimental mouse models of Acinetobacter baumannii infection.Adult male BALB/c mice received intraperitoneally 1 mL saline containing 2 × 10 CFU of susceptible and multiresistant A. baumannii. Two hours after bacterial challenge, animals received 1 mg/kg of colistin, 1 mg/kg of pexiganan, or 1 mg/kg of colistin plus 1 mg/kg of pexiganan.Blood culture positivity, the quantities of bacteria in the intra-abdominal fluid, the rate of lethality and immunological studies, such as immunophenotyping and NK cytotoxicity, were evaluated.In the in vitro study, A. baumannii showed susceptibility to colistin and pexiganan and a strong synergy was observed by testing colistin combined with pexiganan with fractionary inhibitory concentration index of 0.312 for both strains.In the in vivo study colistin or pexiganan alone showed a good antimicrobial efficacy. When colistin was combined with pexiganan, the positive interaction produced low bacterial counts that were statistically significant versus singly treated groups. For both strains the highest rate of survival was observed in combined-treated groups (90%).Pexiganan increased NK cytotoxic activity over the levels of infected and colistin-treated animals.In conclusion, pexiganan combined with colistin was found to be efficacious against A. baumannii infection.
- Published
- 2016