Correlation of posaconazole minimum fungicidal concentration and time kill test against nine Candida species

OBJECTIVES: We evaluated the in vitro activity of posaconazole against nine Candida species using minimum fungicidal concentration (MFC) measurements and time-kill methods. METHODS: MFCs of posaconazole were determined for 209 clinical isolates (32 Candida albicans, 30 Candida glabrata, 21 Candida tropicalis, 29 Candida krusei, 28 Candida parapsilosis sensu stricto, 50 Candida inconspicua, 13 Candida kefyr, 3 Candida lusitaniae and 3 Candida guilliermondii) and 7 ATCC Candida strains. The following strains were tested in time-kill studies: 3 strains each of C. glabrata, C. kefyr, C. guilliermondii and C. lusitaniae; 2 C. tropicalis; 4 C. albicans; 4 C. inconspicua; 9 C. krusei; 12 C. parapsilosis; and 7 ATCC strains. RESULTS: Posaconazole was fungicidal in both MFC and time-kill experiments (at 2 mg/L within 48 h in time-kill assays) against each C. krusei, C. inconspicua and C. lusitaniae strain and was fungistatic against each C. albicans, C. glabrata, C. tropicalis and C. guilliermondii strain. For the C. parapsilosis strains, posaconazole MFCs were 相似文献   

Antifungal susceptibility of Candida spp. isolated from pediatric patients: a survey of 4 children's hospitals

Candida species are the most common cause of fungal infections in hospitalized patients. Recent studies have reported a relative reduction in the rates of infection caused by Candida albicans and a shift toward non-albicans Candida spp. Data on the distribution and susceptibility of Candida spp. from children's hospitals are limited. Clinical isolates of Candida were collected from 4 US children's hospitals in 2003. Broth dilution MICs for amphotericin B, fluconazole, voriconazole, caspofungin, posaconazole, and ravuconazole were performed according to National Committee for Clinical Laboratory Standards-approved methodology. A total of 179 clinical isolates were identified and included. Of 179, 77 (43%) were C. albicans. Candida parapsilosis isolates were the second most frequently identified (57/175, 32%), followed by Candida glabrata, Candida tropicalis, and Candida lusitaniae (approximately 8% each). Caspofungin was the most active agent in vitro against all Candida spp. Fluconazole resistance was seen among C. glabrata, C. tropicalis, and Candida krusei isolates. Newer azoles had improved activity against fluconazole-resistant isolates of Candida. Among isolates of C. parapsilosis, nearly 20% were resistant to amphotericin B. The current study highlights the emergence of C. parapsilosis as a distinct pediatric pathogen with clinical and therapeutic implications. Furthermore, our current susceptibility data include newer antifungal agents that appear to be quite active in vitro and may provide new therapeutic options for the treatment of serious yeast infections in children.     

National surveillance of species distribution in blood isolates of Candida species in Japan and their susceptibility to six antifungal agents including voriconazole and micafungin

OBJECTIVES: The aim of this study was to evaluate species distribution and antifungal susceptibility of Candida blood isolates in Japan. METHODS: In a 1 year surveillance programme, 535 Candida blood isolates were collected. Identification of species was followed by examination with the broth microdilution method, as described in NCCLS M27-A2, of antifungal susceptibility to six agents, including voriconazole and micafungin, with readings after 24 and 48 h of incubation. RESULTS: The overall species distribution was: 41% Candida albicans, 23% Candida parapsilosis, 18% Candida glabrata, 12% Candida tropicalis and 2% Candida krusei. The concentrations of fluconazole necessary to inhibit 90% of the isolates (MIC(90)) at 24/48 h were 0.25/1 mg/L for C. albicans, 0.5/2 mg/L for C. parapsilosis, 4/32 mg/L for C. glabrata and 4/>128 mg/L for C. tropicalis. Percentages of fluconazole resistance were 1.8% for C. albicans, 0.8% for C. parapsilosis, 5.2% for C. glabrata and 3.2% for C. tropicalis, taking the tendency of trailing growth of C. tropicalis into account. MIC(90) of voriconazole was 0.5 mg/L, although 35% of isolates less susceptible (>/=16 mg/L) to fluconazole showed resistance (>/=2 mg/L). Micafungin was very active against all species (MIC(90), 0.03 mg/L) except for C. parapsilosis (MIC(90), 2 mg/L). CONCLUSIONS: These data suggest that, in Japan, the species distribution of Candida bloodstream infections and the fluconazole resistance rate are similar to those reported previously in North America and Europe. Voriconazole and micafungin appear to have strong in vitro activity against Candida blood isolates, although continuing surveillance and further clinical research are needed.     

In vitro susceptibility of 245 yeast isolates to amphotericin B, 5-fluorocytosine, ketoconazole, fluconazole and itraconazole.

The in vitro activity of amphotericin B, 5-fluorocytosine, ketoconazole, fluconazole and itraconazole was tested against 245 yeast strains isolated from clinical specimens (68 Candida albicans, 74 Candida tropicalis, 43 Candida krusei, 28 Candida glabrata, 19 Candida parapsilosis, 8 Candida lusitaniae and 5 Candida guilliermondii). An agar dilution method was employed to carry out testing. Minimal inhibitory concentrations to restrain 90% of isolate growth (MIC90) ranged from 0.12 to 2 mg/l for amphotericin B and for 5-fluorocytosine, from 0.03 to 8 mg/l for ketoconazole, from 0.05 to 50 mg/l for itraconazole and from 0.1 to > 100 mg/l for fluconazole. Among the azole derivatives, the most active was ketoconazole, followed by itraconazole. Only 1 strain of C. albicans was resistant to amphotericin B (MIC > 4 mg/l). Both C. tropicalis and C. krusei responded poorly to fluconazole and the former to itraconazole as well. The species most susceptible to the antifungal agents tested was C. glabrata and the most resistant were C. tropicalis and C. krusei.     

Trends in frequency and in vitro susceptibilities to antifungal agents,including voriconazole and anidulafungin,of Candida bloodstream isolates. Results from a six-year study (1996-2001)

The frequency of isolation and antifungal susceptibility patterns to established and two new antifungal agents were determined for 218 Candida spp isolates causing bloodstream infection from 1996 to 2001. Overall, 41.7% of the candidemias were due to C. albicans, followed by C. parapsilosis (22%), C. tropicalis (16.1%), C. glabrata (11.9%), C. krusei (6%) and miscellaneous Candida spp (2.3%). Isolates of C. albicans C. parapsilosis and C. tropicalis (80% of isolates) were highly susceptible to fluconazole (94 to 100% at /= 32 microg/ml).     

Stable susceptibility of Candida blood isolates to fluconazole despite increasing use during the past 10 years

The prevalence of drug-resistant bacterial pathogens is very high in Taiwan. Accordingly, there was great concern that the introduction of fluconazole would result in rapid emergence of drug-resistant yeasts. Thus, we recommended in 1991 that fluconazole be used for treatment only. To explore the impact of this policy fluconazole susceptibility of Candida species blood culture isolates and outcome of patients with nosocomial candidaemia were monitored prospectively at National Taiwan University Hospital during 1994-2000. The MICs of fluconazole were determined by the disc diffusion method. There were 1095 episodes of nosocomial candidaemia during 1994-2000. Candida albicans was the most common species (50.4%), followed by Candida tropicalis (20.5%), Candida parapsilosis (14.2%) and Candida glabrata (12.0%). There were 0-2 isolates of Candida krusei per year. The incidence of nosocomial candidaemia and the proportion of C. glabrata peaked in 1996 and decreased thereafter. Fluconazole susceptibility was determined for 552 Candida blood isolates. Only 0.7% of blood isolates were resistant to fluconazole. Fluconazole susceptibility was 94.0% in 1994-1995 and 97.9% in 1999-2000 (P = 0.06). Attributable mortality for patients with nosocomial candidaemia was 43.2% in 1994-1995 and was 25% in 2000 (P = 0.005). Despite an increase in the incidence of nosocomial fungal infection and increased consumption of fluconazole from 1994 to 2000, there was no significant change in the susceptibility to fluconazole for bloodstream isolates of Candida species. These findings appear to be attributed to several factors. These include low prevalence of C. krusei and C. glabrata, changing patterns of use of antifungal drugs and broad-spectrum antibiotics, and efforts to improve the rational use of antifungal agents at our hospital.     

Commercial systems for fluconazole susceptibility testing of yeasts: comparison with the broth microdilution method

Fluconazole susceptibility was tested in 100 clinical yeast isolates (65 Candida albicans, 13 C. glabrata, 8 C. tropicalis, 7 C. parapsilosis, 3 Saccharomyces cerevisiae, 1 each of C. krusei, C. lusitaniae, Cryptococcus neoformans, Rhodotorula glutinis) and two control strains (Candida krusei ATCC 6258, C. parapsilosis ATCC 22019) using broth microdilution (reference method), disk diffusion, Etest strips, Sensititre YeastOne, Candifast, Integral System Yeasts. Using M27-A breakpoints, isolates were classified as susceptible (81%), susceptible-dose dependent or Resistant with broth dilution. Rates of concordance with the reference method were good for Sensititre YeastOne, Etest and disc-diffusion (81.2%-94.7%) but very low for the Candifast (3.1%) and Integral System (16.6%), which classified most susceptible isolates as resistant. Lack of standardisation (inoculum, medium composition) and non-objective interpretation schemes may be the cause of their poor performance. Sensititre YeastOne, Etest and disc-diffusion are potentially useful for fluconazole antifungal susceptibility testing of yeasts in clinical laboratories.     

Patterns of amphotericin B killing kinetics against seven Candida species

In a previous study tolerance to amphotericin B (AMB) was found among Candida parapsilosis and C. dubliniensis strains by seeding the whole volumes of wells used for MIC determinations, and minimum fungicidal concentrations (MFC) for non-C. albicans Candida strains were demonstrated to be above the levels safely achievable in serum. As an extension of that study, we performed time-kill assays with 26 blood culture isolates (6 C. albicans, 5 C. parapsilosis, 5 C. krusei, 4 C. glabrata, 3 C. lusitaniae, and 3 C. tropicalis isolates), 3 oropharyngeal C. dubliniensis isolates, 3 AMB-susceptible isolates (ATCC 90028, ATCC 22019, ATCC 6254), and 6 AMB-resistant isolates (ATCC 200955, ATCC 200956, ATCC 200950, ATCC 200951, ATCC 200952, ATCC 200953) using RPMI 1640 medium and 0.12 to 32 microg of AMB per ml and determined the numbers of CFU per milliliter at 0, 2, 4, 8, 12, 24, and 48 h. MFCs and time-kill patterns were species specific (MFCs, < or =1 microg/ml for all C. dubliniensis and C. albicans isolates except AMB-resistant strain ATCC 200955; MFCs, 2 to >16 microg/ml for the other isolates). The times required to reach the fungicidal endpoint (99.9% killing) at four times the MIC were 2 h for C. albicans and C. dubliniensis, 16 h for C. glabrata, 24 h for C. parapsilosis and C. lusitaniae, and > or =40 h for C. tropicalis and C. krusei. The killing rate increased as the AMB concentration was increased up to 2 microg/ml. The highest killing rates were achieved for C. albicans, C. dubliniensis, and C. lusitaniae, while viable C. tropicalis, C. krusei, and C. parapsilosis cells were present after 48 h (MICs, < or =2 microg/ml) when AMB was used at 2 microg/ml. Time-kill curves and MFCs can detect viable cells after 48 h when AMB is used at > or =2 microg/ml. The failure of AMB treatment could be due to its poor killing activity against some species at the concentrations reached in patients' serum.     

In vitro antifungal activity of FK463, a new water-soluble echinocandin-like lipopeptide

The antifungal activity of FK463 against 72 recent clinical isolates of Candida albicans (24), Candida glabrata (17), Candida tropicalis (11), Candida krusei (8) and Candida parapsilosis (12) was compared with those of amphotericin B, fluconazole and itraconazole by means of a broth microdilution method specified by the National Committee for Clinical Laboratory Standards (NCCLS) document M27-A. The lowest drug concentration at which 90% of the population was inhibited (MIC(90)) of FK463 against C. albicans, C. glabrata, C. tropicalis, C. krusei and C. parapsilosis was 0.0156, 0. 0156, 0.0313, 0.125 and 1 mg/L, respectively. FK463 exhibited broad-spectrum activity against clinically important Candida spp. (MIC range < or =0.0039-2 mg/L), and its MICs for such fungi were lower than those of other antifungal agents tested. The minimum fungicidal concentrations for Candida spp. did not differ by more than two-fold from the MICs. Results from pre-clinical evaluations performed to date indicate that FK463 should be a potent parenteral antifungal agent.     

Susceptibilities to amphotericin B and fluconazole of Candida species in Taiwan Surveillance of Antimicrobial Resistance of Yeasts 2006

Susceptibilities to amphotericin B and fluconazole of 964 Candida isolates collected in Taiwan Surveillance of Antimicrobial Resistance of Yeasts in 2006 were determined. There were 419 (43.5%) Candida albicans, 246 (25.5%) Candida tropicalis, 211 (21.9%) Candida glabrata, 62 (6.4%) Candida parapsilosis, 14 (1.5%) Candida krusei, and 12 (1.2%) others. Interestingly, 16 of the 17 amphotericin B-resistant isolates were non-albicans Candida species. The resistant rate to amphotericin B has decreased from 2.5% in 2002 to 1.8% in 2006. On the other hand, there were 132 C. tropicalis, 14 C. krusei, 10 C. albicans, and 9 C. glabrata isolates that had MICs to fluconazole > or =64 microg/mL. The prevalence of isolates with such high MICs was significantly higher than that in 2002 (17.1% versus 1.9%). Our results further indicate that most of the isolates with MICs to fluconazole > or =64 microg/mL exhibited the "trailing" phenomenon.     

Activity of a new triazole, Sch 56592, compared with those of four other antifungal agents tested against clinical isolates of Candida spp. and Saccharomyces cerevisiae.

Sch 56592 is a new triazole agent with potent, broad-spectrum antifungal activity. The in vitro activities of Sch 56592, itraconazole, fluconazole, amphotericin B, and flucytosine (5-FC) against 404 clinical isolates of Candida spp. (382 isolates) and Saccharomyces cerevisiae (22 isolates) were investigated. In vitro susceptibility testing was performed by a broth microdilution method performed according to National Committee for Clinical Laboratory Standards guidelines. Overall, Sch 56592 was very active (MIC at which 90% of isolates are inhibited [MIC90], 0.5 microgram/ml) against these yeast isolates. Sch 56592 was most active against Candida tropicalis, Candida parapsilosis, candida lusitaniae, and Candida stellatoidea (MIC90, < or = 0.12 microgram/ml) and was least active against Candida glabrata (MIC90, 2.0 micrograms/ml). Sch 56592 was 2- to 32-fold more active than amphotericin B and 5-FC against all species except C. glabrata. By comparison with the other triazoles, Sch 56592 was equivalent to itraconazole and greater than or equal to eightfold more active than fluconazole. On the basis of these results, Sch 56592 has promising antifungal activity, and further in vitro and in vivo investigations are warranted.     

Flow cytometry antifungal susceptibility testing of pathogenic yeasts other than Candida albicans and comparison with the NCCLS broth microdilution test

Candida species other than Candida albicans frequently cause nosocomial infections in immunocompromised patients. Some of these pathogens have either variable susceptibility patterns or intrinsic resistance against common azoles. The availability of a rapid and reproducible susceptibility-testing method is likely to help in the selection of an appropriate regimen for therapy. A flow cytometry (FC) method was used in the present study for susceptibility testing of Candida glabrata, Candida guilliermondii, Candida krusei, Candida lusitaniae, Candida parapsilosis, Candida tropicalis, and Cryptococcus neoformans based on accumulation of the DNA binding dye propidium iodide (PI). The results were compared with MIC results obtained for amphotericin B and fluconazole using the NCCLS broth microdilution method (M27-A). For FC, the yeast inoculum was prepared spectrophotometrically, the drugs were diluted in either RPMI 1640 or yeast nitrogen base containing 1% dextrose, and yeast samples and drug dilutions were incubated with amphotericin B and fluconazole, respectively, for 4 to 6 h. Sodium deoxycholate and PI were added at the end of incubation, and fluorescence was measured with a FACScan flow cytometer (Becton Dickinson). The lowest drug concentration that showed a 50% increase in mean channel fluorescence compared to that of the growth control was designated the MIC. All tests were repeated once. The MICs obtained by FC for all yeast isolates except C. lusitaniae were in very good agreement (within 1 dilution) of the results of the NCCLS broth microdilution method. Paired t test values were not statistically significant (P = 0.377 for amphotericin B; P = 0.383 for fluconazole). Exceptionally, C. lusitaniae isolates showed higher MICs (2 dilutions or more) than in the corresponding NCCLS broth microdilution method for amphotericin B. Overall, FC antifungal susceptibility testing provided rapid, reproducible results that were statistically comparable to those obtained with the NCCLS method.     

Susceptibilities to amphotericin B and fluconazole of Candida species in TSARY 2002

Susceptibilities to amphotericin B and fluconazole of 909 Candida species collected during the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) in 2002 were determined by the broth microdilution method. There were 395 (43.5%) Candida albicans, 244 (26.8%) C. tropicalis, 187 (20.6%) C. glabrata, 63 (6.9%) C. parapsilosis, 9 (1%) C. krusei, and 11 (1.2%) others. Among them, 23 (2.5%) isolates were resistant to amphotericin B. They consisted of 10 C. glabrata, 6 C. krusei, 3 C. albicans, 1 C. tropicalis, 1 C. parapsilosis, and 2 others. The resistance rate to amphotericin B has increased compared with that of TSARY 1999 (2.5% versus 0.5%). There were 7 C. krusei, 5 C. albicans, 3 C. glabrata, and 2 others isolates resistant to fluconazole. The resistance rate to fluconazole has decreased from 8.4% in 1999 to 1.9% in 2002. A pattern of coresistance to both amphotericin B and fluconazole was observed.     

Minimum fungicidal concentrations of amphotericin B for bloodstream Candida species

Minimum fungicidal concentrations (MFCs) of amphotericin B were obtained for 165 bloodstream isolates (104 Candida parapsilosis, 14 C.glabrata, 13 C.tropicalis, 15 C.krusei, and 19 C.albicans) and 36 C.dubliniensis from oropharyngeal infections. Minimum inhibitory concentrations (MICs) were determined by the M27-A microdilution method. MFCs (> or =99.9% killing) were obtained following MIC determination (inoculum size, 10(4) CFU/ml) by seeding the entire volume of all clear wells. The best fungicidal activity was for C. albicans, (MFC90 1 microg/ml) and the lowest for C.parapsilosis, C.tropicalis and C.glabrata (MFC90 16 microg/ml). Although MFCs were > or =16x MIC for some isolates, including C. glabrata, the overall MFCs were > or =2x MICs. However, major differences between MICs and MFCs were observed for C.parapsilosis and C.dubliniensis (3.8% and 8.9%, respectively, were tolerant: MFC > or =32MIC). MFCs for C.tropicalis and C. glabrata were > or =2 microg/ml. By this more stringent method we found substantial differences from those previously reported between amphotericin B MIC and MFCs for Candida spp.     

Bloodstream infections due to Candida species: SENTRY antimicrobial surveillance program in North America and Latin America, 1997-1998

An international program of surveillance of bloodstream infections (BSI) in the United States, Canada, and Latin America detected 306 episodes of candidemia in 34 medical centers (22 in the United States, 6 in Canada, and 6 in Latin America) in 1997 and 328 episodes in 34 medical centers (22 in the United States, 5 in Canada, and 7 in Latin America) in 1998. Of the 634 BSI, 54.3% were due to Candida albicans, 16.4% were due to C. glabrata, 14.9% were due to C. parapsilosis, 8.2% were due to C. tropicalis, 1.6% were due to C. krusei, and 4.6% were due to other Candida spp. The percentage of BSI due to C. albicans decreased very slightly in the United States between 1997 and 1998 (56.2 to 54.4%; P = 0.68) and increased in both Canada (52.6 to 70.1%; P = 0.05) and Latin America (40.5 to 44. 6%; P = 0.67). C. glabrata was the second most common species observed overall, and the percentage of BSI due to C. glabrata increased in all three geographic areas between 1997 and 1998. C. parapsilosis was the third most prevalent BSI isolate in both Canada and Latin America, accounting for 7.0 and 18.5% of BSI, respectively. Resistance to fluconazole (MIC, >/=64 microgram/ml) and itraconazole (MIC, >/=1.0 microgram/ml) was observed infrequently in both 1997 (2.3 and 8.5%, respectively) and 1998 (1.5 and 7.6%, respectively). Among the different species of Candida, resistance to fluconazole and itraconazole was observed in C. glabrata and C. krusei, whereas isolates of C. albicans, C. parapsilosis, and C. tropicalis were all highly susceptible to both fluconazole (98.9 to 100% susceptible) and itraconazole (96.4 to 100% susceptible). Isolates from Canada and Latin America were generally more susceptible to both triazoles than U.S. isolates were. Continued surveillance appears necessary to detect these important changes.     

Distribution and antifungal susceptibility of Candida species causing candidemia from 1996 to 1999

Susceptibilities to amphotericin B and fluconazole of 383 Candida species isolated from blood were determined. Candida albicans was the most common species (55.6%), followed by Candida parapsilosis (17.5%), Candida tropicalis (16.5%), Candida glabrata (5.2%), Candida guilliermondii (2.3%), and others (2.9%). All but three isolates, Candida ciferrii, C. tropicalis, and C. glabrata, one each, were susceptible to amphotericin B. A total of 367 (95.8%) and 15 (4.2%) isolates were susceptible and susceptible-dose dependent to fluconazole, respectively. Only one isolate, a C. glabrata, was resistant to fluconazole. Few patients (13%) having prior fluconazole treatments may explain the low rate of resistance to fluconazole in this study.     

In Vitro Susceptibilities of Candida and Cryptococcus neoformans Isolates from Blood Cultures of Neutropenic Patients

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.     

Prospective Study of Candida Species in Patients at a Comprehensive Cancer Center

Since most nosocomial systemic yeast infections arise from the endogenous flora of the patient, we prospectively evaluated the species stratification and antifungal susceptibility profile of Candida spp. associated with heavy colonization and systemic infection in patients at Memorial Sloan-Kettering Cancer Center in New York. A total of 349 Candida isolates were obtained from 223 patients during the later half of 1998. Cancer was the most common underlying disease, occurring in 91% of the patients, including 61.8% with organ and 23.7% with hematological malignancies; 4.4% of the patients had AIDS. Candida albicans was the predominant species (67.3%); among 114 non-albicans Candida spp., C. glabrata (45.6%) was the most frequent, followed by C. tropicalis (18.4%), C. parapsilosis (16.6%), and C. krusei (9.6%). The overall resistance to triazole-based agents among all yeast isolates was 9.4 and 10.8% for fluconazole and itraconazole, respectively. A total of 5% of C. albicans strains were resistant to triazole antifungals, whereas 30.8 and 46.2% of C. glabrata strains were resistant to fluconazole (MIC > or = 64 microg/ml) and itraconazole (MIC > or = 1 microg/ml), respectively. A significant association was observed between prior treatment with triazole and isolation of fluconazole-resistant C. albicans (P = 0.005, OR 36), although this relationship was not seen in C. glabrata isolates (P = 0.4). This study reinforces the importance of periodic, prospective surveillance of clinical fungal isolates to determine appropriate prophylactic, empiric, and preemptive antifungal therapy for the highly susceptible patient population.     

Trends in species distribution and susceptibility to fluconazole among blood stream isolates of Candida species in the United States

National surveillance of blood stream infections (BSI) attributable to Candida spp. has been limited to date. Recent studies have suggested in increase in the proportion of BSI attributable to non-Candida albicans species and have also raised concerns regarding the emergence of antifungal resistance among Candida spp. The increased utilization of broad-spectrum antifungal agents and the recognition of Candida spp. as prominent pathogens with the potential for developing antifungal resistance, emphasize the need for ongoing surveillance of antifungal susceptibility patterns. In this investigation trends in species distribution and susceptibility to fluconazole among BSI isolates of Candida spp. referred to our laboratory by United States hospitals were evaluated over the 7-year period from 1992 to 1998. A total of 1579 BSI isolates from more than 50 medical centers were processed. Overall, C. albicans accounted for 52% of isolates followed by C. glabrata (18%), C. parapsilosis (15%), C. tropicalis (11%), and C. krusei (2%). The proportion of BSI isolates that were C. albicans ranged from 45% in 1992 to 60% in 1998. Among the non-C. albicans isolates, C. glabrata succeeded C. parapsilosis as the most common species beginning in 1995. Overall, the susceptibility of all Candida species (C. albicans plus all other species) to fluconazole remained stable (MIC90, 16 micrograms/mL). The fluconazole MIC90 for C. albicans was 0.5-2.0 micrograms/ml for all years studied except 1995 (8.0 micrograms/mL) and was 1.0 microgram/mL overall. The present study suggests a continued prominent role of C. albicans as a cause of BSI, and a constant level of susceptibility of Candida BSI isolates to fluconazole over 7 years. These data should serve as a baseline for future surveillance efforts for anti-fungal agents tested against yeast BSI isolates.     

Susceptibility of clinical isolates of Candida lusitaniae to five systemic antifungal agents

OBJECTIVES: The aim of the present study was to expand the MIC database for Candida lusitaniae in order to further determine its antifungal susceptibility pattern. METHODS: The activities of amphotericin B, fluconazole, itraconazole, voriconazole and flucytosine were determined in vitro against 80 clinical isolates of C. lusitaniae. A set of 59 clinical isolates of Candida albicans and of 51 isolates of Candida glabrata was included to compare the susceptibilities to amphotericin B. The MICs were determined by Etest with RPMI 1640 agar, and with both this medium and antibiotic medium 3 (AM3) agar for testing of amphotericin B. RESULTS: All isolates were highly susceptible to fluconazole. The susceptibility to itraconazole was good; only 4% of isolates had dose-dependent susceptibility (MICs 0.25-0.5 mg/L). Voriconazole was very active in vitro (100% of isolates were inhibited at < or =0.094 mg/L). Flucytosine MICs ranged widely (0.004->32 mg/L). The set included 19% of flucytosine-resistant isolates. For amphotericin B, 100% of isolates were inhibited at < or =0.75 mg/L (MIC(50) 0.047 mg/L; MIC(90) 0.19 mg/L) and at < or =4 mg/L (MIC(50) 0.25 mg/L; MIC(90) 0.75 mg/L) on RPMI and on AM3, respectively. A single isolate was categorized as resistant to amphotericin B (MIC 0.75 and 4 mg/L on RPMI and on AM3, respectively). Amphotericin B thus appeared very active in vitro against C. lusitaniae. Whatever the test medium, the level of susceptibility of C. lusitaniae to amphotericin B did not differ much from those of C. albicans and C. glabrata. CONCLUSION: C. lusitaniae appears to be susceptible to amphotericin B, azole antifungal agents, and, to a lesser extent, flucytosine.