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One hundred seven Candida bloodstream isolates (51 C. albicans, 24 C. glabrata, 13 C. parapsilosis, 13 C. tropicalis, 2 C. dubliniensis, 2 C. krusei, and 2 C. lusitaniae strains) from patients treated with amphotericin B alone underwent in vitro susceptibility testing against amphotericin B using five different methods. Fifty-four isolates were from patients who failed treatment, defined as death 7 to 14 days after the incident candidemia episode, having persistent fever of ≥5 days' duration after the date of the incident candidemia, or the recurrence of fever after two consecutive afebrile days while on antifungal treatment. MICs were determined by using the Clinical Laboratory Standards Institute (formally National Committee for Clinical Laboratory Standards) broth microdilution procedure with two media and by using Etest. Minimum fungicidal concentrations (MFCs) were also measured in two media. Broth microdilution tests with RPMI 1640 medium generated a restricted range of MICs (0.125 to 1 µg/ml); the corresponding MFC values ranged from 0.5 to 4 µg/ml. Broth microdilution tests with antibiotic medium 3 produced a broader distribution of MIC and MFC results (0.015 to 0.25 µg/ml and 0.06 to 2 µg/ml, respectively). Etest produced the widest distribution of MICs (0.094 to 2 µg/ml). However, none of the test formats studied generated results that significantly correlated with therapeutic success or failure.

ABSTRACTOne hundred seven Candidabloodstream isolates (51 C. albicans, 24 C. glabrata, 13 C. parapsilosis, 13 C. tropicalis, 2 C. dubliniensis, 2 C. krusei, and 2 C. lusitaniaestrains) from patients treated with amphotericin B alone underwent in vitro susceptibility testing against amphotericin B using five different methods. Fifty-four isolates were from patients who failed treatment, defined as death 7 to 14 days after the incident candidemia episode, having persistent fever of ≥5 days' duration after the date of the incident candidemia, or the recurrence of fever after two consecutive afebrile days while on antifungal treatment. MICs were determined by using the Clinical Laboratory Standards Institute (formally National Committee for Clinical Laboratory Standards) broth microdilution procedure with two media and by using Etest. Minimum fungicidal concentrations (MFCs) were also measured in two media. Broth microdilution tests with RPMI 1640 medium generated a restricted range of MICs (0.125 to 1 μg/ml); the corresponding MFC values ranged from 0.5 to 4 μg/ml. Broth microdilution tests with antibiotic medium 3 produced a broader distribution of MIC and MFC results (0.015 to 0.25 μg/ml and 0.06 to 2 μg/ml, respectively). Etest produced the widest distribution of MICs (0.094 to 2 μg/ml). However, none of the test formats studied generated results that significantly correlated with therapeutic success or failure.

ABSTRACTTo determine the incidence of Candidabloodstream infections (BSI) and antifungal drug resistance, population-based active laboratory surveillance was conducted from October 1998 through September 2000 in two areas of the United States (Baltimore, Md., and the state of Connecticut; combined population, 4.7 million). A total of 1,143 cases were detected, for an average adjusted annual incidence of 10 per 100,000 population or 1.5 per 10,000 hospital days. In 28% of patients, CandidaBSI developed prior to or on the day of admission; only 36% of patients were in an intensive care unit at the time of diagnosis. No fewer than 78% of patients had a central catheter in place at the time of diagnosis, and 50% had undergone surgery within the previous 3 months. Candida albicanscomprised 45% of the isolates, followed by C. glabrata(24%), C. parapsilosis(13%), and C. tropicalis(12%). Only 1.2% of C. albicansisolates were resistant to fluconazole (MIC, =64 µg/ml), compared to 7% of C. glabrataisolates and 6% of C. tropicalisisolates. Only 0.9% of C. albicansisolates were resistant to itraconazole (MIC, =1 µg/ml), compared to 19.5% of C. glabrataisolates and 6% of C. tropicalisisolates. Only 4.3% of C. albicansisolates were resistant to flucytosine (MIC, =32 µg/ml), compared to <1% of C. parapsilosisand C. tropicalisisolates and no C. glabrataisolates. As determined by E-test, the MICs of amphotericin B were =0.38 µg/ml for 10% of Candidaisolates, =1 µg/ml for 1.7% of isolates, and =2 µg/ml for 0.4% of isolates. Our findings highlight changes in the epidemiology of CandidaBSI in the 1990s and provide a basis upon which to conduct further studies of selected high-risk subpopulations.

ABSTRACTA two-laboratory study was performed to evaluate the correlation between the NCCLS M27-A and EUCAST microdilution procedures for antifungal testing of Candidaspp. A panel of 109 bloodstream isolates was tested against amphotericin B, flucytosine, fluconazole, and itraconazole. Overall, the agreement was 92% and the intraclass correlation coefficient was 0.90 (P< 0.05).

ABSTRACTVisual determination of MIC end points for azole antifungal agents can be complicated by the trailing growth phenomenon. To determine the incidence of trailing growth, we performed testing of in vitro susceptibility to fluconazole and itraconazole using the National Committee for Clinical Laboratory Standards broth microdilution M27-A reference procedure and 944 bloodstream isolates of seven Candidaspp., obtained through active population-based surveillance between 1998 and 2000. Of 429 C. albicansisolates, 78 (18.2%) showed trailing growth at 48 h in tests with fluconazole, and 70 (16.3%) showed trailing in tests with itraconazole. Of 118 C. tropicalisisolates, 70 (59.3%) showed trailing growth in tests with fluconazole, and 35 (29.7%) showed trailing in tests with itraconazole. Trailing growth was not observed with any of the other five Candidaspp. tested (C. dubliniensis, C. glabrata, C. krusei, C. lusitaniae, and C. parapsilosis). To confirm whether or not isolates that showed trailing growth in fluconazole and/or itraconazole were resistant in vitro to these agents, all isolates that showed trailing growth were retested by the sterol quantitation method, which measures cellular ergosterol content rather than growth inhibition after exposure to azoles. By this method, none of the trailing isolates was resistant in vitro to fluconazole or itraconazole. For both agents, a 24-h visual end point or a spectrophotometric end point of 50% reduction in growth relative to the growth control after 24 or 48 h of incubation correlated most closely with the result of sterol quantitation. Our results indicate that MIC results determined by either of these end point rules may be more predictive of in vivo outcome for isolates that give unclear visual end points at 48 h due to trailing growth.

ABSTRACTThe in vitro activity of voriconazole was compared to those of itraconazole and amphotericin B against the mold forms of 304 isolates of three dimorphic fungi, Blastomyces dermatitidis,Coccidioides immitis, and Histoplasma capsulatum. MICs were determined by a broth microdilution adaptation of the National Committee for Clinical Laboratory Standards M27-A procedure. RPMI 1640 medium was used for tests with voriconazole and itraconazole, whereas Antibiotic Medium 3 with 2% glucose was used for amphotericin B. Minimum fungicidal concentrations (MFCs) were also determined. Amphotericin B was active against all three dimorphic fungi, with MICs at which 90% of the isolates tested are inhibited (MIC90s) of 0.5 to 1 μg/ml. Itraconazole had MIC90s of 0.06 μg/ml for H. capsulatum, 0.125 μg/ml for B. dermatitidis, and 1 μg/ml for C. immitis. The MIC90s of voriconazole were 0.25 μg/ml for all three fungi. Amphotericin B was fungicidal for B. dermatitidisand H. capsulatumwith MFCs at which 90% of strains tested are killed (MFC90s) of 0.5 and 2 μg/ml, respectively. It was less active against C. immitis, with MFCs ranging from 0.5 to >16 μg/ml. Voriconazole and itraconazole were lethal for most isolates of B. dermatitidis, with MFC50s and MFC90s of 0.125 and 4 μg/ml, respectively. Both azoles were fungicidal for some isolates of H. capsulatum, with MFC50s of 2 and 8 μg/ml for itraconazole and voriconazole, respectively; neither had a lethal effect upon C. immitis. Our results suggest that voriconazole possesses promising activity against these important human pathogens.