Global Distribution and Outcomes for Candida Species Causing Invasive Candidiasis: Results from an International Randomized Double-Blind Study of Caspofungin Versus Amphotericin B for the Treatment of Invasive Candidiasis

Abstract

In a randomized study, caspofungin was compared with amphotericin B for the treatment of invasive candidiasis in a total of 239 adults from 56 sites in 20 countries. This study provided a unique opportunity to assess the frequency and outcome of invasive candidiasis caused by different Candida species worldwide, and the results are presented here. Efficacy was primarily assessed at the end of intravenous therapy using a modified intent-to-treat (MITT) analysis. This analysis was performed on 224 of the 239 patients enrolled in the study. Attempts were made to collect baseline Candida isolates from all patients for species identification at a central laboratory. Yeasts were identified to the species level using two commercial systems and microscopic examination. Viable baseline isolates were recovered from 210 of the 224 (94%) patients included in the MITT analysis. Candida albicans was the most frequently isolated species in all regions and was responsible for 45% of cases overall. Nevertheless, the majority of cases of infection were caused by non- albicans Candida species. In the USA and Canada, Candida glabrata was the second most commonly isolated pathogen (18%). In contrast, Candida parapsilosis and Candida tropicalis accounted for 55% of cases in Latin America. Outcomes were comparable for patients treated with caspofungin (74% overall; 64% and 80% for infections due to Candida albicans and non- albicans species) and amphotericin B (62% overall; 58% and 68% for infections due to Candida albicans and non- albicans species), and were generally similar across continents. The distribution of Candida species isolated from patients enrolled in a clinical trial may not be representative of pathogens causing invasive candidiasis in the general population. Nevertheless, our findings may affect the regional choice of empirical antifungal therapy for seriously ill patients with suspected or documented invasive candidiasis since different Candida species have varying susceptibility to conventional antifungal drugs.

Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem

“…Meaningful large-scale surveys of antifungal susceptibility and resistance conducted over time would not be possible without a standardized microdilution or disk diffusion method for performing the in vitro studies (48,49,183,212,221,224). Many such surveys have now been published and include studies of isolates from ICU patients and of nosocomial and community-onset BSIs in several different countries (5,10,11,33,34,35,41,49,92,104,107,108,113,183,207,212,217,218,221,224,230,234,259,279,289,290,323). Furthermore, studies of trends in resistance to commonly used antifungal agents such as fluconazole (10,33,47,212,259) and comparative analyses of licensed and newly introduced antifungal agents (10,49,157,183,207,217,230,…”

Nationwide Study of Candidemia, Antifungal Use, and Antifungal Drug Resistance in Iceland, 2000 to 2011

“…Although Candida albicans remains the most common Candida species isolated from blood, it currently causes only approximately 50% of candidemia cases (14)(15)(16)(17)(18). However, significant geographical differences in species distribution exist.…”

“…However, significant geographical differences in species distribution exist. The proportion of candidemia caused by C. albicans ranges from 37% in Latin America up to 70% in the Nordic countries (10,11,14). Furthermore, the relative proportions of non-albicans Candida pathogens also vary between the northern and southern parts of the world.…”

Susceptibility of Candida spp. clinical isolates to antimycotics and disinfectants

“…Although Candida albicans is still the most common strain resulting in yeast infections, contributing towards both invasive and non-invasive forms of candidiasis, the number of patients infected by C. glabrata, C. tropicalis, C. parapsilosis and C. krusei has increased in recent years [1][2][3]. Microorganisms prevalent in the hospital environment can potentially colonise patients and cause infections.…”