Efficacy of the amphibian peptide distinctin in a neutropenic mouse model of staphylococcal sepsis

Abstract OBJECTIVE: To investigate the efficacy of distinctin in a neutropenic mouse model of staphylococcal sepsis. DESIGN: Prospective, randomized, and controlled animal study. SETTING: Research laboratory in a University Hospital. SUBJECTS: BALB/c male mice. INTERVENTIONS: Mice were rendered neutropenic by injecting cyclophosphamide (200 mg/kg of body weight/day) on days -4 and -2 preinfection. Infection was induced at time 0 by intraperitoneal injection of 1 x 10(9) colony forming units of the staphylococcal strain. For each model, all animals were randomized to receive intravenous isotonic sodium chloride solution, 1 mg/kg distinctin, and 10 mg/kg imipenem, 10 mg/kg vancomycin, 10 mg/kg teicoplanin or 10 mg/kg linezolid alone, or combined with 1 mg/kg distinctin. MEASUREMENTS AND MAIN RESULTS: Lethality, bacterial growth in blood and peritoneum, spleen, liver, and mesenteric lymph nodes. RESULTS: All combined regimen showed lower lethality rates than singly treated-groups. Distinctin plus vancomycin or teicoplanin exerted the lowest lethality rate. All regimens were significantly superior to controls at reducing blood, spleen, peritoneum, liver and mesenteric lymph node complex bacterial burdens, whereas all combined treated groups were higher effective than singly treated groups. CONCLUSION: Our data indicate that distinctin alone or combined with other antibiotics may be useful in treating severe staphylococcal infections.