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).     

In vitro susceptibilities of bloodstream isolates of Candida species to six antifungal agents: results from a population-based active surveillance programme, Barcelona, Spain, 2002-2003

OBJECTIVES: The antifungal drug susceptibilities of 351 isolates of Candida species, obtained through active laboratory-based surveillance in the period January 2002-December 2003, were determined (Candida albicans 51%, Candida parapsilosis 23%, Candida tropicalis 10%, Candida glabrata 9%, Candida krusei 4%). METHODS: The MICs of amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole and caspofungin were established by means of the broth microdilution reference procedure of the European Committee on Antibiotic Susceptibility Testing. RESULTS AND CONCLUSIONS: Amphotericin B and flucytosine were active in vitro against all strains. A total of 24 isolates (6.8%) showed decreased susceptibility to fluconazole (MIC > or = 16 mg/L) and 43 (12.3%) showed decreased susceptibility to itraconazole (MIC > or = 0.25 mg/L). Voriconazole and caspofungin were active in vitro against the majority of isolates, even those that were resistant to fluconazole.     

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.     

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.     

Susceptibility patterns of Candida species recovered from Canadian intensive care units

OBJECTIVE: The objective of this study was to determine the speciation and susceptibility patterns of Candida species recovered from Canadian intensive care units (ICUs) during a 1-day point-prevalence study on fungal colonization/infection in Canadian ICUs. METHODS AND SETTING: Blood, urine, respiratory tract, rectal, and wound fungal cultures were performed for 357 patients present at any time during a single-day 24-hour period in 35 Canadian ICUs. Comparative in vitro activities of amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, micafungin, anidulafungin, and aminocandin were determined. RESULTS: Four hundred fifteen yeasts (409 Candida species and 6 non-Candida yeasts) were recovered. Almost 50% of the patients were found to have positive respiratory tract or rectal cultures. Candida albicans accounted for 72% of the Candida species isolated, followed by Candida glabrata (16%), Candida tropicalis (5%), Candida parapsilosis (3%), Candida krusei (2%), and other Candida species or nonspeciated isolates (2%). Minimum inhibitory concentrations (milligrams per liter) at which 90% of the strains were inhibited were 0.06 for micafungin as well as anidulafungin, 0.12 for voriconazole, 0.25 for itraconazole, posaconazole, as well as aminocandin, 1 for amphotericin B, and 4 for fluconazole. Only 4% of the isolates were resistant to fluconazole and/or itraconazole. CONCLUSIONS: Candida albicans is the predominant species colonizing Canadian ICU patients. Overall, the triazoles, both older and new compounds, and the echinocandins have excellent in vitro antifungal activities against Candida species recovered from Canadian ICUs patients.     

Candida bloodstream infections: comparison of species distributions and antifungal resistance patterns in community-onset and nosocomial isolates in the SENTRY Antimicrobial Surveillance Program, 2008-2009

Community-onset (CO) candidemia, defined as a positive blood culture taken at or within 2 days of hospital admission, represents a distinct clinical entity associated with substantial morbidity and mortality. Reference MIC results from the SENTRY Antimicrobial Surveillance Program (2008-2009) were analyzed to compare the antifungal resistance patterns and species distributions from patients with CO and nosocomial bloodstream infections (BSI) in 79 medical centers. Among 1,354 episodes of BSI, 494 (36.5%) were classified as CO and 860 (63.5%) as nosocomial in origin. More than 95% of the isolates from both BSI types were contributed by Candida albicans (48.4%), C. glabrata (18.2%), C. parapsilosis (17.1%), C. tropicalis (10.6%), and C. krusei (2.0%). C. albicans was more common in CO BSI (51.0%) than nosocomial BSI (46.9%), whereas C. parapsilosis and C. krusei were more common in nosocomial BSIs (18.1 and 2.7%, respectively) than in CO BSIs (15.4 and 0.8%, respectively). C. glabrata and C. tropicalis were comparable in both CO (18.4 and 10.5%, respectively) and nosocomial (18.1 and 10.6%, respectively) episodes. Resistance to azoles (fluconazole, posaconazole, and voriconazole) and echinocandins (anidulafungin, caspofungin, and micafungin) was uncommon (<5%) in CO BSI using recently established Clinical and Laboratory Standards Institute breakpoint criteria. Resistance to echinocandins (anidulafungin [3.8%], caspofungin [5.1%], and micafungin [3.2%]) and azoles (fluconazole [7.7%], posaconazole [5.1%], and voriconazole [6.4%]) was most prevalent among nosocomial BSI isolates of C. glabrata. CO candidemia is not uncommon and appears to be increasing worldwide due to changing health care practices. Although resistance to the azoles and echinocandins remains uncommon among CO isolates, we demonstrate the emergence of nosocomial occurrences of C. glabrata expressing resistance to both monitored classes of antifungal agents.     

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.     

In vitro activities of isavuconazole and other antifungal agents against Candida bloodstream isolates

Isavuconazole is the active component of the new azole antifungal agent BAL8557, which is entering phase III clinical development. This study was conducted to compare the in vitro activities of isavuconazole and five other antifungal agents against 296 Candida isolates that were recovered consecutively from blood cultures between 1995 and 2004 at a tertiary care university hospital. Microdilution testing was done in accordance with CLSI (formerly NCCLS) guideline M27-A2 in RPMI-1640 MOPS (morpholinepropanesulfonic acid) broth. The antifungal agents tested were amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole, and isavuconazole. C. albicans was the most common species, representing 57.1% of all isolates. There was no trend found in favor of non-Candida albicans species over time. In terms of MIC(50)s, isavuconazole was more active (0.004 mg/liter) than amphotericin B (0.5 mg/liter), itraconazole (0.008 mg/liter), voriconazole (0.03 mg/liter), flucytosine (0.125 mg/liter), and fluconazole (8 mg/liter). For isavuconazole, MIC(50)s/MIC(90)s ranged from 000.2/0.004 mg/liter for C. albicans to 0.25/0.5 mg/liter for C. glabrata. Two percent of isolates (C. glabrata and C. krusei) were resistant to fluconazole; C. albicans strains resistant to fluconazole were not detected. There were only two isolates with MICs for isavuconazole that were >0.5 mg/liter: both were C. glabrata isolates, and the MICs were 2 and 4 mg/liter, respectively. In conclusion, isavuconazole is highly active against Candida bloodstream isolates, including fluconazole-resistant strains. It was more active than itraconazole and voriconazole against C. albicans and C. glabrata and appears to be a promising agent against systemic Candida infections.     

In vitro susceptibility of Candida species to five antifungal agents in a German university hospital assessed by the reference broth microdilution method and Etest

OBJECTIVES: The aim of this study is to evaluate the susceptibilities of Candida spp. to the common antifungal agents in a German university hospital. Since quick results of in vitro testing are desirable, Etest and the CLSI broth microdilution (BMD) method (reference method) were compared, focusing on the validity of early readings. METHODS: A total of 512 Candida spp. isolates, including 174 from primarily sterile sites, were collected in the clinical routine. The yeasts were differentiated by CHROMagar and verified by API 20C AUX if necessary. In vitro susceptibilities to amphotericin B, flucytosine, fluconazole, voriconazole and caspofungin were determined using the BMD method described in the CLSI (formerly NCCLS) M27-A2 document and Etest. MICs were noted after 24 and 48 h of incubation. RESULTS: The most frequently isolated species was Candida albicans. Among the non-albicans species, Candida glabrata was the most prevalent, followed by Candida tropicalis, Candida parapsilosis and Candida krusei. MICs (mg/L) at which 90% of the strains were inhibited were 1 for amphotericin B, 32 for flucytosine, 8 for fluconazole, 0.25 for voriconazole and 1 for caspofungin. Susceptibility to fluconazole was 85.0% for C. glabrata and 5.3% for C. krusei, almost all other isolates were susceptible in over 90% except very rare species. The 48 h MIC values of Etest and BMD were in agreement (no more than 2 log(2) dilutions) in 88.7% to 98.1% with categorical agreement rates of 91.6% to 98.2%, depending on the antifungal agent. Comparison of the 24 h MICs of both BMD and Etest with the 48 h MICs of the reference method showed categorical agreement in 94.9% to 99.2%. For caspofungin, however, a comparison of the categorical agreement was not possible due to the lack of interpretive breakpoints. The order of frequency and the resistance patterns of the isolates from primarily sterile sites and those of isolates from non-sterile sites did not differ. CONCLUSIONS: No alarming resistances against the agents tested were found; however, owing to the relatively high frequency of C. glabrata with elevated fluconazole MICs, this species and, to a certain extent, C. krusei must be taken into consideration when choosing antifungal agents for calculated therapy. Etest is a reliable method for the susceptibility testing of Candida spp. and the 24 h readings of both Etest and BMD can serve as helpful preliminary results in most cases.     

Initial results from a longitudinal international surveillance programme for anidulafungin (2003)

OBJECTIVES: This longitudinal study evaluated the in vitro activity of anidulafungin against 880 clinical yeast isolates and 68 mould isolates from 64 medical centres in North America, Latin America and Europe. METHODS: MICs of anidulafungin, amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, ketoconazole and voriconazole were determined using reference method (M27-A2) guidelines. The M38-A reference method was used for the filamentous fungi, including determination of minimum effective concentrations (MECs) of anidulafungin. RESULTS: Anidulafungin was more active when compared with fluconazole and itraconazole for Candida albicans (MIC(90), 0.06 mg/L), Candida tropicalis (MIC(90), 0.06 mg/L), Candida glabrata (MIC(90), 0.12 mg/L), Candida krusei (MIC(90), 0.06 mg/L) and Candida lusitaniae (MIC(90), 1 mg/L) as well as the less-often encountered yeast species. Anidulafungin was less active against Candida parapsilosis, Candida guilliermondii and Candida famata (MIC(50), 1-2 mg/L). Anidulafungin also exhibited excellent activity against all Aspergillus spp. (MEC(90), < or =0.03 mg/L). Anidulafungin was also evaluated comparing two end point reading criteria and two incubation intervals. Data indicate that longer incubation periods do not significantly influence overall MIC ranges. These international surveillance results for anidulafungin confirm the activity observed in studies of smaller numbers of isolates.     

Paradoxical effect of Echinocandins across Candida species in vitro: evidence for echinocandin-specific and candida species-related differences

Paradoxical growth of some Candida isolates occurs at concentrations above the MIC for echinocandins. In 60 Candida bloodstream isolates from cancer patients (20 C. albicans isolates and 10 isolates each of C. parapsilosis, C. tropicalis, C. krusei, and C. glabrata), paradoxical growth was more frequent with caspofungin than micafungin or anidulafungin, was unrelated to MIC, and was strikingly absent in C. glabrata isolates.     

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 susceptibilities of clinical isolates of Candida species, Cryptococcus neoformans, and Aspergillus species from Taiwan: surveillance of multicenter antimicrobial resistance in Taiwan program data from 2003

The susceptibilities of nonduplicate isolates to six antifungal agents were determined for 391 blood isolates of seven Candida species, 70 clinical isolates (from blood or cerebrospinal fluid) of Cryptococcus neoformans, and 96 clinical isolates of four Aspergillus species, which were collected in seven different hospitals in Taiwan (as part of the 2003 program of the study group Surveillance of Multicenter Antimicrobial Resistance in Taiwan). All isolates of Candida species other than C. glabrata and C. krusei were susceptible to fluconazole. Among the 59 C. glabrata isolates, 16 (27%) were not susceptible to fluconazole, and all were dose-dependently susceptible or resistant to itraconazole. For three (5.1%) C. glabrata isolates, voriconazole MICs were 2 to 4 microg/ml, and for all other Candida species isolates, voriconazole MICs were /=2 microg/ml were 100% (3 isolates) for C. krusei, 11% (23 of 207 isolates) for Candida albicans, 3.0% (2 of 67 isolates) for Candida tropicalis, 20% (12 of 59 isolates) for C. glabrata, and 0% for both Candida parapsilosis and Candida lusitaniae. For three (4%) Cryptococcus neoformans isolates, fluconazole MICs were >/=16 microg/ml, and two (3%) isolates were not inhibited by 1 mug of amphotericin B/ml. For four (4.2%) of the Aspergillus isolates, itraconazole MICs were 8 microg/ml. Aspergillus flavus was less susceptible to amphotericin B, with the MICs at which 50% (1 microg/ml) and 90% (2 microg/ml) nsrsid417869\delrsid7301351 of isolates were inhibited being twofold greater than those for Aspergillus fumigatus and Aspergillus niger. All Aspergillus isolates were inhibited by 相似文献   

Association of fluconazole area under the concentration-time curve/MIC and dose/MIC ratios with mortality in nonneutropenic patients with candidemia

The present study tested in vitro susceptibility of Candida bloodstream isolates to fluconazole to determine if the ratio of the fluconazole area under the concentration-time curve (AUC) or weight-normalized daily dose (dose(wn)) to MIC correlated with mortality. Fluconazole susceptibility and outcome data were determined for 77 patients with a positive Candida blood culture between 2002 and 2005. The most commonly isolated Candida species were C. albicans (64%), C. glabrata (14%), C. parapsilosis (8%), C. tropicalis (6%), and C. lusitaniae (4%). Only two isolates were classified as fluconazole resistant by the CLSI M27-A2 method. Fluconazole MICs were highest against C. glabrata relative to other Candida species. Overall the crude mortality assessed at hospital discharge was 19.4% (n = 15). Mortality rates by species were as follows: C. albicans, 16.3%; C. glabrata, 36.4%; C. parapsilosis, 0%; C. tropicalis, 0%; C. lusitaniae, 33.3%. A mortality rate of 50% was noted among patients infected with nonsusceptible isolates (MIC > or = 16 microg/ml) compared to 18% for patients infected with susceptible (MIC < or = 8 microg/ml) isolates (P = 0.17). The fluconazole dose(wn)/MIC (24-h) values were significantly higher for the 62 survivors (13.3 +/- 10.5 [mean +/- standard deviation]) compared to the 15 nonsurvivors (7.0 +/- 8.0) (P = 0.03). The fluconazole AUC/MIC (24 h) values also trended higher for survivors (775 +/- 739) compared to nonsurvivors (589 +/- 715) (P = 0.09). These data support the dose-dependent properties of fluconazole. Underdosing fluconazole against less-susceptible Candida isolates has the potential to increase the risk of mortality associated with candidemia.     

In vitro activity of a new semisynthetic echinocandin, LY-303366, against systemic isolates of Candida species, Cryptococcus neoformans, Blastomyces dermatitidis, and Aspergillus species.

The in vitro activities of LY-303366, a new semisynthetic echinocandin, and comparators amphotericin B, 5-fluorocytosine, fluconazole, and ketoconazole against 205 systemic isolates of Candida species, Cryptococcus neoformans, Blastomyces dermatitidis, and Aspergillus species were determined. LY-303366 had MICs of < or = 0.32 microg/ml for all Candida albicans (n = 99), Candida glabrata (n = 18), and Candida tropicalis (n = 10) isolates tested. LY-303366 was also active against Aspergillus species (minimum effective concentration at which 90% of the isolates are inhibited, 0.02 microg/ml) (n = 20), was less active against Candida parapsilosis (MIC at which 90% of the isolates are inhibited [MIC90], 5.12 microg/ml) (n = 10), and was inactive against C. neoformans (MIC90, >10.24 microg/ml) (n = 15) and B. dermatitidis (MIC90, 16 microg/ml) (n = 29).     

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.     

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.     

The European Confederation of Medical Mycology (ECMM) survey of candidaemia in Italy: antifungal susceptibility patterns of 261 non-albicans Candida isolates from blood

OBJECTIVES: To analyse the in vitro antifungal susceptibility of 261 non-albicans Candida bloodstream strains isolated during the European Confederation of Medical Mycology survey of candidaemia performed in Lombardia, Italy (September 1997-December 1999). METHODS: In vitro susceptibility to flucytosine, fluconazole, itraconazole, posaconazole and voriconazole was determined using the broth microdilution method described in the NCCLS M27-A guidelines. Etest strips were used to assess susceptibility to amphotericin B. In vitro findings were correlated with the patient's underlying condition and previous antifungal treatment. RESULTS: MICs (mg/L) at which 90% of the strains were inhibited were, respectively, 2 for flucytosine, 8 for fluconazole, 0.5 for itraconazole, 0.25 for voriconazole and 0.25 for posaconazole. Amphotericin B MIC endpoints were <0.50 mg/L in all the isolates tested. Flucytosine resistance was detected in 19 isolates (7%), mainly among Candida tropicalis strains (30%). Innate or secondary fluconazole resistance was detected in 13 strains (5%). Among the 13 patients with fluconazole-resistant Candida bloodstream infection, three were HIV positive, including one treated with fluconazole for oral candidosis; the four who were HIV negative had received the azole during the 2 weeks preceding the candidaemia. Cross-resistance among fluconazole and other azoles was a rare event. CONCLUSIONS: Resistance is still uncommon in non-albicans Candida species recovered from blood cultures. However, in fungaemias caused by C. tropicalis, Candida glabrata and Candida krusei, there is a high prevalence of resistance to fluconazole and flucytosine. Fluconazole resistance should be suspected in patients treated previously with azoles, mainly those with advanced HIV infection.     

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.     

Comparative study of disc diffusion and microdilution methods in susceptibility testing of micafungin against Candida species

OBJECTIVES: To compare the Clinical Laboratory Standards Institute CLSI M44-A disc diffusion (DD) and M27-A2 broth microdilution (MD) methods for determining the susceptibility of Candida spp. to micafungin (FK463). PATIENTS AND METHODS: A total of 355 clinical yeast isolates including 270 Candida albicans, 45 Candida glabrata, 24 Candida krusei, 11 Candida tropicalis and 5 Candida parapsilosis were studied. The MIC of micafungin was determined by following the CLSI M27-A2 guidelines (MD). Endpoints were defined as the lowest concentration of micafungin resulting in partial inhibition (IC(50)) of visual growth after 24/48 h of incubation at 35 degrees C. Final concentrations were 0.008-4 mg/L of micafungin. DD testing was performed using a CLSI M44-A document with 2.5 mug micafungin discs. Zone diameter endpoints were read after 24/48 h of incubation at 35 degrees C. Arbitrary breakpoints were 4 mg/L for MD and 15 mm for DD. RESULTS: The best correlation was observed when we read MD 48 h/DD 24 and 48 h (97%). When the reading was MD 24 h/DD 24 and 48 h the percentage of correlation was 95.2%. CONCLUSIONS: The DD method performs well for testing the susceptibility of Candida spp. to micafungin. More studies involving more Candida strains with elevated MIC values are needed.