Efficacies of caspofungin and a combination of caspofungin and meropenem in the treatment of murine disseminated candidiasis.
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 2x10(6) 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 <0.075 micro g/ml and >64 micro g/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.
Ozcan
Sema Keceli
SK
Department of Microbiology and Clinical Microbiology, Kocaeli University, Medical Faculty, Kocaeli, Turkey. keceliozcan@yahoo.com
Budak
Fatma
F
Willke
Ayse
A
Filiz
Serdar
S
Costur
Pelin
P
Dalcik
Hakki
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D000077336:Caspofungin; D015169:Colony Count, Microbial; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D054714:Echinocandins; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D055666:Lipopeptides; D008297:Male; D000077731:Meropenem; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms; D013845:Thienamycins / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D013845:Thienamycins; D000077336:Caspofungin; D000077731:Meropenem