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Although development of resistance in Candida albicans to amphotericin B is considered rare, C. albicans was persistently recovered from a 28-year-old man after a prolonged course of broad-spectrum antimicrobial therapy for a pancreatic abscess. Determination of the MICs of drugs for C. albicans in Sabouraud broth revealed MICs of 2.5 mg/l amphotericin B, greater than 40 mg/l ketoconazole, 2.5 mg/l miconazole, and greater than 40 mg/l 5-fluorocytosine. Synergy testing revealed a MIC of 0.3 mg/l amphotericin B in the presence of 2.5 mg/l 5-fluorocytosine. When intravenous 5-fluorocytosine was added to the patient's antifungal regimen, achieving levels of 125 mg/l, negative blood cultures resulted for the first time. This suggests there may be a clinical use for in vitro synergy testing as an adjunct to guide antifungal therapy for fungemia due to amphotericin B-resistant C. albicans.
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PMID:Disseminated candidiasis due to amphotericin B-resistant Candida albicans. 140 37

The in vitro activity of amphotericin B, flucytosine and fluconazole against 95 yeasts causing fungemia in a single institution over the last eight years was determined by a broth macromethod recommended by the National Committee for Clinical Laboratory Standards. All strains were inhibited by amphotericin B concentrations of < or = 1 microgram/ml. With flucytosine in most species the MIC50 was between 0.12 and 0.25 microgram/ml and the MIC90 was between 0.25 and 1 microgram/ml. One exception with flucytosine was Candida krusei, with an MIC50 and MIC90 of 16 micrograms/ml and 32 micrograms/ml, respectively. Overall, 12% of the isolates needed at least 8 micrograms/ml of fluconazole to be inhibited. Fluconazole was very active against Candida albicans, Candida tropicalis and Cryptococcus neoformans, with MIC50 ranging from 0.12 to 0.5 microgram/ml and MIC90 of 1 microgram/ml, and somewhat less active against Candida parapsilosis (MIC50 of 1 microgram/ml and MIC90 of 4 micrograms/ml). Fluconazole exhibited poor in vitro activity against Candida krusei (MIC50 and MIC90 of 64 micrograms/ml) and Torulopsis glabrata (MIC50 of 4 micrograms/ml and MIC90 of 16 micrograms/ml). High MICs of fluconazole were found for four strains of Candida albicans, one with an MIC of 4 micrograms/ml and three (5.7%) with MICs of > or = 16 micrograms/ml. Previous exposure to fluconazole could be demonstrated in two of these strains. Further work must be done in order to determine appropriate breakpoints of antifungal agents, to assess the clinical relevance of azole resistance in yeasts causing bloodstream infections and to identify risk factors for infections with azole-resistant yeasts.
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PMID:In vitro activity of amphotericin B, flucytosine and fluconazole against yeasts causing bloodstream infections. 764 5

Unlike the situation with many antimicrobial agents, there is limited experience with the use of amphotericin B during pregnancy. Although reports of fungal infections during pregnancy have been published, few describe fungemia with either Candida or Torulopsis species. We present a case of fungemia due to Torulopsis glabrata that occurred during pregnancy and that was treated with amphotericin B. Drug concentrations were measured in placental tissue, cord serum, and infant serum at delivery. Although the last dose of amphotericin B was administered 4 weeks before delivery, the concentrations in all three specimens were still within the MIC ranges for most strains of Candida albicans and T. glabrata as measured by broth dilution. We speculate that persistent tissue concentrations of amphotericin B most likely contributed to the sustained hypokalemia in the mother and the increased creatinine level in the infant. In the latter case, placental tissue may have served as the reservoir from which amphotericin B was slowly released into fetal circulation.
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PMID:Use of amphotericin B during pregnancy: case report and review. 801 17

The most common yeast species that act as agents of human disease are Candida albicans, Candida tropicalis, Candida glabrata, Candida parapsilosis, and Cryptococcus neoformans. The incidence of infections by other yeasts has increased during the past decade. The most evident emerging pathogens are Malassezia furfur, Trichosporon beigelii, Rhodotorula species, Hansenula anomala, Candida lusitaniae, and Candida krusei. Organisms once considered environmental contaminants or only industrially important, such as Candida utilis and Candida lipolytica, have now been implicated as agents of fungemia, onychomycosis, and systemic disease. The unusual yeasts primarily infect immunocompromised patients, newborns, and the elderly. The role of central venous catheter removal and antifungal therapy in patient management is controversial. The antibiograms of the unusual yeasts range from resistant to the most recent azoles and amphotericin B to highly susceptible to all antifungal agents. Current routine methods for yeast identification may be insufficient to identify the unusual yeasts within 2 days after isolation. The recognition of unusual yeasts as agents of sometimes life-threatening infection and their unpredictable antifungal susceptibilities increase the burden on the clinical mycology laboratory to pursue complete species identification and MIC determinations. Given the current and evolving medical practices for management of seriously ill patients, further evaluations of the clinically important data about these yeasts are needed.
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PMID:New and emerging yeast pathogens. 866 65

Fluconazole-resistant Candida albicans and intrinsically fluconazole-resistant Candida species have been reported as bloodstream isolates. However, an association between the isolation of fluconazole-resistant Candida from the bloodstream and patient risk factors for fungemia has not been established. The purpose of this study was to determine the prevalence of fluconazole resistance in bloodstream isolates of Candida species and Cryptococcus neoformans collected from patients with neutropenia, one of the most important risk factors for fungemia. MICs of voriconazole, fluconazole, itraconazole, ketoconazole, amphotericin B, and flucytosine were determined by the National Committee for Clinical Laboratory Standards M27-A method (1997). Voriconazole, on a per-weight basis, was the most active azole tested. Fluconazole resistance (MIC >/= 64 microg/ml) was not identified in any of the C. albicans (n = 513), Candida parapsilosis (n = 78), Candida tropicalis (n = 62), or C. neoformans (n = 38) isolates tested.
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PMID:In vitro susceptibilities of Candida and Cryptococcus neoformans isolates from blood cultures of neutropenic patients. 1034 71

Candida lipolytica has rarely been reported as a human pathogen. An apparent outbreak of Candida lipolytica fungemia (n = 5 cases) occurred in a pediatric ward over a 9-week period. The five patients infected were hospitalized in three adjacent rooms and cared for by the same healthcare workers. The index patient had central venous catheter-related fungemia, whereas the second patient, who was in the adjacent single room, had transient fungemia. Three additional cases of fungemia occurred in patients with hematological disorders who shared the same room; all three patients had central venous catheters and had been receiving oral fluconazole prophylaxis (50 mg/day for more than 3 weeks) at the time of infection. In vitro susceptibility testing of the strains showed that the MIC of fluconazole for all the isolates was 32 microg/ml. Random amplified polymorphic DNA analysis provided evidence of the clonal origin of the isolates, but the source of the outbreak was not identified. All four patients with persistent fungemia were successfully treated via catheter removal or empiric amphotericin B treatment. This outbreak shows the potential for the nosocomial epidemic transmission of Candida lipolytica.
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PMID:Nosocomial cluster of Candida lipolytica fungemia in pediatric patients. 1089 34

Cryptococcus spp. other than Cryptococcus neoformans are generally considered nonpathogenic to humans. There are only 15 case reports of disease in humans caused by Cryptococcus laurentii infection. Underlying diseases and predisposing risk factors seem to play an important role in these cases. Our patient is the first case of an extremely low birth weight infant with C. laurentii fungemia reported in the English literature. In our case, the MIC of amphotericin B for C. laurentii was 0.25 to 1 microg/ml and the patient had a good outcome following the administration of amphotericin B at 10 mg/kg combined with central venous catheter removal. There will undoubtedly be an increasing occurrence of unusual fungal infections accompanying further advances in medicine. A high degree of suspicion and improvements in the techniques for culture and identification will contribute to the earlier diagnosis and treatment of unusual fungal infections.
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PMID:Cryptococcus laurentii fungemia in a premature neonate. 1128 97

The aim of this study was to test the antifungal susceptibility of 262 bloodstream yeast isolates (164 Candida albicans strain, 88 non-albicans Candida spp. and 10 non-Candida yeasts) recovered from 169 surgical, neonatal, critically ill intensive care unit patients (ICU), and cancer patients (mixed patient population) to amphotericin B (AmB), fluconazole (FLU), 5-flucytosine (5-FC), itraconazole (ITRA), ketoconazole (KETO), miconazole (MICO), and nystatin (NYS), in order to correlate in-vitro resistance to fluconazole with the outcome of fungemia. The agar disk diffusion test was used to assess the susceptibility of the 262 bloodstream yeasts isolates. In addition, 78 strains isolated from cancer patients were also tested with the E-test. There were no differences in the susceptibility of the various C. albicans strains tested, except in 40 isolates from surgery patients, which showed a somewhat lower susceptibility to KETO and MICO to (3.7-5.5% resistance). There were no C. albicans strains resistant to AmB, NYS, or FLU. There were slight differences in the susceptibility patterns of the 88 non-albicans Candida spp. (NAC) isolates. Resistance to AmB and NYS appeared in 1 strain of C. guillermondii (minimum inhibitory concentration; MIC to AmB; 4 microg/ml) and in 1 strain of C. parapsilosis (MIC to NYS, 8 microg/ml and MIC to AmB, 2 microg/ml). All other NACs were susceptible to both polyenes (AmB and NYS). Nine of the 11 strains of C. krusei were resistant to FLU (MIC >or= 64 microg/ml), the 2 exceptions showed, respectively, MICs for FLU of 6 and 32 microg/ml ("dose-dependent" susceptibility). However, only 2 of 29 C. glabrata strains were fully FLU-resistant (MIC >or= 64 microg/ml), 27 being susceptible with MIC values of 0.5-8 microg/ml. Apart from 9 C. krusei and 2 C. glabrata strains, 2 C. parapsilosis strains and 1 strain of C. tropicalis were also FLU-resistant. Among the 88 NACs, 17.04% were FLU-resistant and 3.7% were KETO- and ITRA-resistant. Resistance to 5-FC and AmB was minimal. We compared the outcomes of patients infected with FLU-resistant vs FLU-susceptible yeasts in 161 evaluable patients treated with FLU. Attributable mortality was significantly higher (19.0% vs 8.6%; P < 0.01) in patients infected with the FLU-resistant yeasts.
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PMID:Antifungal susceptibility of 262 bloodstream yeast isolates from a mixed cancer and non-cancer patient population: is there a correlation between in-vitro resistance to fluconazole and the outcome of fungemia? 1181 May 69

Reduced susceptibility to fluconazole (RSF) is relatively common in non-albicans Candida isolates and in Candida albicans recovered from HIV-infected patients with relapsing Candida stomatitis or esophagitis. However, little clinical data on bloodstream infections caused by C. albicans with RSF is available. We analyzed 116 episodes of C. albicans fungemia detected over an 11-year period. Four patients (3.4%) had a blood isolate of C. albicans with RSF. Fluconazole MICs were 16 (3 SDD strains) and 128 microg/ml (1 resistant strain), respectively. Three of the patients were HIV (+) and the fourth was a liver transplant recipient. All of them had been previously treated with an azole compound. The liver recipient had breakthrough fungemia while being treated with 400 mg of preemptive fluconazole despite having an MIC of 16 microg/ml. Fluconazole clinical failure was documented in two of the remaining three cases. Only five other patients with C. albicans fungemia caused by fluconazole-resistant strains (>or=64 microg/ml) are described in the literature. Candida albicans fungemia produced by strains with RSF is still uncommon. It should be suspected in patients previously treated with azole agents or with breakthrough fungemia. In our experience, fluconazole remains a safe option for the treatment of most C. albicans fungemias, although surveillance seems advisable.
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PMID:Frequency and clinical significance of bloodstream infections caused by C albicans strains with reduced susceptibility to fluconazole. 1245 23

The incidence of nosocomial Candida fungemia increased 36-fold from 1981 (0.8/10,000 discharges) to 2000 (28.8/10,000 discharges) at the National Taiwan University Hospital, a 2000-bed teaching hospital in northern Taiwan. To understand the current status of resistance to available antifungal agents among Candida species causing invasive infections, the in vitro susceptibilities of 222 isolates (collected from July, 1999-June, 2001) were determined. Among all of the Candida species tested, 6% and 7% were resistant to fluconazole and itraconazole, respectively. The MIC90 values of voriconazole and amphotericin B were 0.5 and 1 microg/ml, respectively, although some isolates of C. krusei (amphotericin B and voriconazole MIC, >64 microg/ml) and C. tropicalis and C. glabrata (voriconazole MICs, >64 microg/ml) were less susceptible to voriconazole or amphotericin B. About one-half of the C. glabrata isolates belonged to susceptible dose-dependent (SDD, 36%) or resistant (12%) categories for fluconazole and 96% belonged to SDD (56%) or resistant (40%) category for itraconazole. When compared with fluconazole susceptibility data of blood Candida isolates recovered from patients treated at the same hospital (NTUH) from two different time periods (January, 1994, to June, 1995, and January, 1997, to June, 1999 described in previous reports), the incidence of increased susceptibility of non-krusei Candida isolates to fluconazole was evident. This trend of increasing susceptibility for fluconazole did not correlate to the increasing use of this agent in the hospital. None of the random amplified polymorphic DNA patterns generated by arbitrarily primed PCR using four random oligonucleotide primers for 14 isolates, which exhibited fluconazole MICs of > or = 16 microg/ml, were identical, indicating an absence of clonal dissemination among these isolates in the hospital.
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PMID:Emergence of nosocomial candidemia at a teaching hospital in Taiwan from 1981 to 2000: increased susceptibility of Candida species to fluconazole. 1252 28


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