Differential in vitro activity of anidulafungin, caspofungin and micafungin against Candida parapsilosis isolates recovered from a burn unit

Abstract

Recent studies suggest that differences in antifungal activity among echinocandins may exist. In this study, the activities of three echinocandins (anidulafungin, caspofungin, and micafungin) against Candida parapsilosis isolates from burn unit patients, healthcare workers and the hospital environment were determined. Additionally, the effect of these echinocandins on the cell morphology of caspofungin-susceptible and caspofungin-non-susceptible isolates was assessed using scanning electron microscopy (SEM). The C. parapsilosis isolates obtained from patients were susceptible to anidulafungin, but were less so to caspofungin and micafungin. Isolates obtained from healthcare workers or environmental sources were susceptible to all antifungals. SEM data demonstrated that although anidulafungin and caspofungin were equally active against a caspofungin-susceptible C. parapsilosis strain, they differed in their ability to damage a caspofungin-non-susceptible strain, for which lower concentrations of anidulafungin (1 mg/L) than of caspofungin (16 mg/L) were needed to induce cellular damage and distortion of the cellular morphology. To determine whether the difference in the antifungal susceptibility of C. parapsilosis isolates to anidulafungin as compared to the other two echinocandins could be due to different mutations in the FKS1 gene, the sequences of the 493-bp region of this gene associated with echinocandin resistance were compared. No differences in the corresponding amino acid sequences were observed, indicating that differences in activity between anidulafungin and the other echinocandins are not related to mutations in this region. The results of this study provide evidence that differences exist between the activities of anidulafungin and the other echinocandins.

Prevalence, Distribution, and Antifungal Susceptibility Profiles of Candida parapsilosis , C. orthopsilosis , and C. metapsilosis in a Tertiary Care Hospital

“…We detected a multiechinocandin-, multiazole-resistant phenotype of C. parapsilosis sensu stricto, as reported by Moudgal et al (24) and Vazquez and colleagues (12). The development and subsequent nosocomial expansion of echinocandin-and azole-resistant C. parapsilosis sensu stricto have important clinical implications.…”

Anidulafungin versus Caspofungin in a Mouse Model of Candidiasis Caused by Anidulafungin-Susceptible Candida parapsilosis Isolates with Different Degrees of Caspofungin Susceptibility

“…Echinocandins possess reduced in vitro activity against C. parapsilosis (2,(12)(13)(14)(15), and clinical failures due to CAS-R isolates have been reported recently (16,17), especially in patients receiving CAS (18,19). The reduced susceptibility of C. parapsilosis to echinocandins has been related to polymorphisms in the FSK1 gene (16,36,37).…”

“…Specifically, echinocandins, including caspofungin (CAS), micafungin (MICA), and anidulafungin (ANF), have limited toxicity in patients and possess broad-spectrum fungicidal activity against azole-resistant Candida species, making these agents the preferred first-line therapy for many forms of IC (12). Nonetheless, echinocandins demonstrate reduced in vitro activity against C. parapsilosis (1,(12)(13)(14)(15), and failures of echinocandin treatment have been reported in C. parapsilosis IC (16,17). In particular, clinical failure due to CAS-resistant (CAS-R) isolates has been recently reported in patients receiving CAS (18,19).…”

Comparison of Anidulafungin MICs Determined by the Clinical and Laboratory Standards Institute Broth Microdilution Method (M27-A3 Document) and Etest for Candida Species Isolates

“…Although lack of prior evaluations precluded comparisons, the acceptable essential agreement is Ն90% (10). It is unfortunate that C. parapsilosis and C. guilliermondii were among the species with unsuitably low essential agreement, because little information has been gathered in either efficacy clinical trials or molecular studies (5,22,24,31). High MICs (Ͼ0.5 g/ml) were not observed for the clinical isolates of the other species where the essential agreement was low, and therefore those results did not affect the categorical agreement (Tables 2 and 3).…”