Efficacies of caspofungin and a combination of caspofungin and meropenem in the treatment of murine disseminated candidiasis

• Published in: APMIS : acta pathologica, microbiologica et immunologica Scandinavica microbiologica et immunologica Scandinavica, 2006-12, Vol.114 (12), p.829-836
• Main Authors: OZCAN, SEMA KECELI, BUDAK, FATMA, WILLKE, AYSE, FILIZ, SERDAR, COSTUR, PELIN, DALCIK, HAKKI
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Antifungal Agents - pharmacology; Biological and medical sciences; Candida albicans; Candida albicans - drug effects; Candida albicans - growth & development; Candidiasis - drug therapy; Candidiasis - microbiology; Candidiasis - pathology; caspofungin; Colony Count, Microbial; disseminated candidiasis; Drug Synergism; Drug Therapy, Combination; Echinocandins; Fundamental and applied biological sciences. Psychology; Infectious diseases; Kidney - microbiology; Kidney - pathology; Lipopeptides; Male; Medical sciences; meropenem; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Microbiology; Miscellaneous; murine model; Mycology; Peptides, Cyclic - pharmacology; Specific Pathogen-Free Organisms; Thienamycins - pharmacology
• ISSN: 0903-4641; 1600-0463
• DOI: 10.1111/j.1600-0463.2006.apm_450.x

Disseminated candidiasis is relatively common in immunocompromised patients. The treatment protocol of these patients usually includes broad‐spectrum antibiotics and also emprical antifungals initiated due to unresponsiveness to antibiotics. In this study the efficacies of caspofungin and meropenem – separately and together – in mice with disseminated candidiasis were studied. Immunocompetent mice were infected intravenously with 2×106 CFU of Candida albicans. At 24 h postinfection, intraperitoneal therapy was initiated and was continued for 7 days. Therapy groups included those given caspofungin (0.5, 1.25, 5 mg/kg/day), meropenem (20 mg/kg/day), and a combination of the two drugs. The outcome of therapy was evaluated by kidney tissue burden studies and histologic examination. In vitro, drug susceptibilities were tested by checkerboard analysis. Kidney CFU counts showed that mice that had received both drugs had lower residual burdens. Caspofungin was effective at doses of 0.5, 1.25, 5 mg/kg compared to infected untreated controls. In vitro, MICs of caspofungin and meropenem were 64 μg/ml, respectively. Synergism was observed with the combination. Histopathology showed that the degree of inflammation was 25% less and tubular necrosis was more restricted in combined therapy than monotherapy. The results indicate that concurrent caspofungin and meropenem therapy may be beneficial