Effect of omiganan on colonic anastomosis healing in a rat model of peritonitis.

BACKGROUND: This study investigates the effects of the antimicrobial cationic peptide omiganan-alone and combined with the antibiotic imipenem-on colonic anastomosis healing in presence of intraperitoneal sepsis induced in a rodent model of cecal ligation and puncture (CLP). METHODS: Forty male Wistar rats were divided into 5 groups of 8 animals. Group 1 (control group) underwent laparotomy and cecal mobilization and the next day received left colon anastomosis. In group 2 (CLP without treatment), group 3 (CLP + imipenem), group 4 (CLP + omiganan), and group 5 (CLP + omiganan + imipenem), the left colon anastomosis was performed the day after CLP. Imipenem and omiganan were administered by intraperitoneal injection immediately before anastomosis construction and subsequently at 24 h intervals until the 7th postoperative day, when rats were sacrificed. Anastomotic bursting pressure was measured in situ. Tissue samples were collected for determination of hydroxyproline content and histological characteristics. RESULTS: Only rats receiving omiganan + imipenem displayed re-epithelialization, reduced neovascularization of granulation tissue, and a bursting pressure that was similar to that of controls. Omiganan-alone and combined with imipenem-was associated with a better control of inflammatory parameters than imipenem alone. In addition omiganan, like imipenem, counteracted the collagen depletion typical of sepsis. CONCLUSIONS: This experimental study demonstrates the efficacy of the new antimicrobial agent omiganan, alone and in combination with imipenem, in delaying the effects of intraperitoneal sepsis on colonic anastomosis healing and provides evidence of the value of omiganan as a therapeutic agent.

Colistin enhances therapeutic efficacy of daptomycin or teicoplanin in a murine model of multiresistant Acinetobacter baumannii sepsis.

We investigated the efficacy of colistin combined with teicoplanin or daptomycin in an experimental mouse model of multiresistant Acinetobacter baumannii infection. Animal received intraperitoneally 1ml saline containing 2×1010CFU of A. baumannii. Colistin, daptomycin, teicoplanin, and colistin plus daptomycin or teicoplanin were given by intraperitoneal administration 2h after bacterial challenge. A control group received sodium chloride solution. In the in vitro study A. baumannii showed to be susceptible only to colistin with MIC of 2mg/l. In the in vivo study, colistin alone showed a good antimicrobial efficacy. When combined with teicoplanin or daptomycin, colistin produced the lowest bacterial and the best survival rates. In immunological studies, when colistin was associated to daptomycin or teicoplanin, both the number and the cytotoxic activity of NK cells increased. In conclusion, colistin combined with teicoplanin or daptomycin may improve the therapy of multiresistant A. baumannii infection.

Enhanced Efficacy of Combinations of Pexiganan with Colistin Versus Acinetobacter Baumannii in Experimental Sepsis.

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.

Therapeutic efficacy of buforin II and rifampin in a rat model of Acinetobacter baumannii sepsis.

OBJECTIVE: To investigate the efficacy of buforin II and rifampin in an experimental rat model of Acinetobacter baumannii sepsis. DESIGN: Prospective, randomized, controlled animal study. SETTING: Research laboratory in a university hospital. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: The animals received intraperitoneally 1 mL saline containing 2 x 10 colony forming units of A. baumannii ATCC 19606 (model i) or the multiresistant strain (model ii). Immediately after bacterial challenge, animals received intravenously a single dose of isotonic sodium chloride solution (control groups C1 and C2), 1 mg/kg of buforin II, 10 mg/kg of rifampin, and 1 mg/kg of buforin II plus 10 mg/kg of rifampin, respectively. MEASUREMENTS AND MAIN RESULTS: Lethality, bacterial growth in blood and tissue burden, endotoxin, interleukin-6, and tumor necrosis factor-alpha concentrations in plasma. Buforin II showed good antimicrobial activity and achieved a significant reduction of plasma endotoxin and cytokines concentration when compared with control and rifampin-treated groups. Combination among buforin II proved to be the most effective treatment in reducing all variables measured. CONCLUSION: In an experimental model, buforin II and rifampin might have a potential role in the treatment of severe infections due to A. baumannii.