Killing Kinetics of Caspofungin, Micafungin, and Amphotericin B against Candida guilliermondii

Abstract

Amphotericin B (AMB), micafungin, and caspofungin MICs, minimal fungicidal concentrations, and timekilling curves were determined in the presence and absence of 10% inactivated serum. AMB was the only agent with consistent killing activity (time required to achieve 99.9% of growth reduction was 2.1 to 3.2 h). The presence of serum enhanced caspofungin activity but lowered those of micafungin and AMB.Candida guilliermondii is infrequently isolated from blood cultures (1 to 5%) (14), and infections caused by this species have been reported in cancer, surgical, and intensive care unit patients (13)(14), including a pseudo-outbreak of candidemia in a neonatal intensive care unit (23). Malignancy, neutropenia, and bone marrow transplantation have been reported as risk factors for acquiring C. guilliermondii infections (22). Treatment of these infections may present problems, especially for immunocompromised patients; a high percentage of strains have diminished susceptibility to fluconazole (MIC at which 90% of organisms are inhibited, 16 mg/liter) and itraconazole (MIC at which 90% of organisms are inhibited, 1 mg/liter) (17-18). Amphotericin B (AMB), caspofungin, and micafungin have fungicidal activity against some Candida spp. (3)(4)(8)(9), but most studies have focused on Candida albicans and little is known about the killing activity of these agents against C. guilliermondii. A previous evaluation demonstrated that the same AMB MIC may correspond to different killing activities, depending on the Candida species or strain tested, and that each species has a different AMB killing pattern (5). Because the killing kinetics of AMB, caspofungin, and micafungin against C. guilliermondii are unknown, this study aimed to characterize the in vitro pharmacodynamics and fungicidal activities of these drugs against this species. Since these agents are highly protein bound (Ͼ90%) (9, 10, 11), the influence of serum on their in vitro activity has also been evaluated. For the first time, we provide the dynamics of the fungicidal activity of these three agents against C. guilliermondii.Drugs. AMB deoxycholate (Bristol-Myers Squibb, Madrid, Spain) was dissolved in dimethyl sulfoxide, and caspofungin (Merck Sharpe & Dome, Madrid, Spain) and micafugin (Fujisawa Pharmaceutical Company, Japan) were dissolved in water. Further drug dilutions were prepared in standard RPMI 1640 medium (Sigma-Aldrich, Madrid, Spain) as recommended in the M27-A2 document (16).MIC and MFC determination. MICs were determined for 19 C. guilliermondii clinical isolates at least twice (on different days) in RPMI and RPMI plus 10% inactivated fetal bovine serum (FBS) (Sigma-Aldrich) by the M27-A2 method but using a higher inoculum (2.5 ϫ 10 4 CFU/ml). Complement was inactivated by heating the undiluted serum (30 min, 60°C). Both MIC 2 and MIC 0 (Ն50% and 100% growth reduction, respectively) were determined for caspofungin and micafungin and MIC 0 s for AMB. Minimal fungicidal concentrations (MFCs) were obtained by transferring 0.1 ml from all clear MIC wells (...

Susceptibility testing of Candida albicans isolated from oropharyngeal mucosa of HIV+ patients to fluconazole, amphotericin B and Caspofungin: killing kinetics of caspofungin and amphotericin B against fluconazole resistant and susceptible isolates

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

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Breakthrough C. parapsilosis and C. guilliermondii blood stream infections in allogeneic hematopoietic stem cell transplant recipients receiving long-term caspofungin therapy

“…C. parapsilosis and C. guilliermondii, which have been reported to exhibit decreased susceptibility to echinocandins in vitro. [1][2][3] While only 5 episodes of candidemia (C. glabrata n=3, C. albicans n=1, and C. krusei n=1) were observed in 487 allogeneic hematopoietic stem cell transplant (HSCT) recipients between January 2000 and December 2004, 3 cases of candidemias (C. parapsilosis n=2, C. guilliermondii n=1) occurred out of 170 HSCT recipients from January 2005 to July 2006. The 3 patients were receiving long-term caspofungin therapy.…”