Caspofungin Use in Patients with Invasive Candidiasis Caused by Common Non- albicans Candida Species: Review of the Caspofungin Database

Abstract

Increasing rates of invasive candidiasis caused by non-albicans Candida species have been reported worldwide. Particular concerns have been raised for C. parapsilosis because of reduced in vitro susceptibility to echinocandins. We identified 212 patients with invasive candidiasis due to non-albicans Candida species (>5 cases per species) in 5 clinical trials of caspofungin monotherapy from the pharmaceutical sponsor's (Merck and Co., Inc.) database: 71 cases were caused by C. parapsilosis, 65 by C. tropicalis, 54 by C. glabrata, 10 by C. krusei, 9 by C. guilliermondii, and 5 by C. lusitaniae. One hundred sixty-seven cases caused by C. albicans were also identified. Efficacy was assessed at the end of caspofungin therapy. Success (favorable overall response) required favorable clinical and microbiological responses. The mean APACHE II scores were 16.5 in the non-albicans group and 15.7 in the C. albicans group. Neutropenia at study entry was more common in the non-albicans group (12%) than in the C. albicans group (5%). The median duration of caspofungin therapy was 14 days in both groups. The success rates were 77% in both groups and at least 70% for each non-albicans species: 74% for C. parapsilosis, 71% for C. tropicalis, 85% for C. glabrata, 70% for C. krusei, 89% for C. guilliermondii, and 100% for C. lusitaniae. The times to negative blood culture were similar for the various species. The overall mortality rates were 26% in the non-albicans group and 29% in the C. albicans group. Drug-related serious adverse events and discontinuations due to caspofungin toxicity were uncommon. Although the sample sizes were limited, caspofungin demonstrated favorable efficacy and safety profiles in the treatment of invasive candidiasis caused by the following non-albicans Candida species: C. parapsilosis, C. tropicalis, C. glabrata, C. krusei, C. guilliermondii, and C. lusitaniae.

Geographic Trends in Invasive Candidiasis

“…Indeed, reports on neonatal candidemia have found C. parapsilosis to be the first or the second most common cause of fungemia [35]. Despite the higher MIC levels of echinocandins against C. parapsilosis strains, data from clinical trials suggest that this class of drug has efficacy when treating patients with C. parapsilosis candidemia [36].…”

Invasive Candidiasis in the Neutropenic Cancer Patient

“…According to IDSA 2009 guidelines, echinocandins should be avoided in patients with C. parapsilosis because of frequently elevated MICs, and in patients with central nervous system infections and endophthalmitis because of poor penetration. Yet caspofungin monotherapy demonstrated efficacy in the treatment of C. parapsilosis, C. tropicalis, C. glabrata, C. krusei, C. guilliermondii, and C. lusitaniae in a retrospective study of 212 patients with IC due to non-albicans Candida species, who were enrolled in five clinical studies [49].…”

Candida parapsilosis Endocarditis Presenting on Native Valve With Cerebrovascular Accident and Myocardial Infarction

“…52 In recent study, although the sample sizes was limited, the efficacy of caspofungin in the treatment of invasive candidiasis was the same as in the amphotericin B, with the overall (clinical and microbiologic) success rate among patients with C. parapsilosis (74%) similar to patients with invasive candidiasis caused by other Candida species, so they can likely be used as a second choice after triazoles as with fewer side effects and same efficacy as amphotericin B. 50,53 Mortality rate for C. parapsilosis IE was similar to overall fungal endocarditis mortality rate (41-43%). 54,55 However, in our study, mortality rate for native valve C. parapsilosis IE was lower.…”