Drug Resistance in Candida albicans and Candida glabrata a

196

123

Thirteen laboratories collaborated to optimize interlaboratory agreement of results of a broth macrodilution procedure for testing three classes of antifungal drugs against pathogenic yeasts. The activities of amphotericin B, flucytosine, and ketoconazole were tested against 100 coded isolates of Candida albicans, Candida tropicalis, Candida parapsilosis, Candida lusitaniae, Torulopsis (Candida) glabrata, and Cryptococcus neoformans. Two starting yeast inoculum sizes (5 x 104 and 2.5 x 103 cells per ml) were compared, and readings were taken after 24 and 48 h of incubation. All other test conditions were standardized. The resultant turbidities in all tubes were estimated visually on a scale from 0 to 4+ turbidity, and MIC-0, MIC-1, and MIC-2 were defined as the lowest drug concentrations that reduced growth to 0, 1+, or 2+ turbidity, respectively. For flucytosine, agreement among laboratories varied between 57 and 87% for different inocula, times of incubation, and end point criteria. Agreement was maximized (85%) when the lower inoculum was incubated for 2 days and the MICs were defined as 1+ turbidity or less. For amphotericin B, variations in test conditions produced much smaller differences in interlaboratory agreement. For ketoconazole, interlaboratory agreement was poorer by all end point criteria. However, MIC-2 endpoints distinguished T. glabrata as resistant compared with the other species. Overall, the studies indicated that readings from the lower inoculum obtained on the second day of reading result in the greatest interlaboratory agreement. In combination with data from previous multicenter studies (National Committee for Clinical Laboratory Standards, Antifungal Susceptibility Testing: Committee

Section: Discussionmentioning

confidence: 66%

Multicenter evaluation of a broth macrodilution antifungal susceptibility test for yeasts

Fromtling

Galgiani

Pfaller

et al. 1993

196

123

“…Prior to the availability of fluconazole, very few strains of C. albicans were identified as azole resistant (12,13). T. glabrata had appeared relatively resistant in vitro under some conditions, but clinical experience with azole treatment was limited (8,(14)(15)(16)21). More recently, there has been an increasing number of C. albicans strains isolated from patients failing fluconazole therapy for either mucosal or deepseated infection (3,23,27).…”

Section: D0870(r)-2-(24-difluorophenyl)-1-(3-[(e)-4-(2233-tetrafmentioning

confidence: 99%

In vitro studies of a new antifungal triazole, D0870, against Candida albicans, Cryptococcus neoformans, and other pathogenic yeasts

Tao

Galgiani

1993

We investigated the effects of various assay conditions on the activity of D0870 against seven species of fungi in the broth macrodilution testing procedure proposed by the National respectively. In contrast, Candida krusei and Torulopsisglabrata had a median MIC.0 of 1.0 ,g/ml. Our studies indicate that the pathogenic yeasts C. albicans and C. neoformans are more susceptible to D0870 than other pathogenic yeasts.

“…The pursuit of drugs effective against this pathogen has been hindered by the resistance of this organism to many drugs and metabolic inhibitors. The nature of the resistance to a few drugs has been identified as related to altered transport, modification of an enzyme, and a change in membrane composition (19,20,25). However, a broad-spectrum resistance, identified initially as combined resistance to benomyl and methotrexate and later as resistance to four additional agents, appears to be an inherent characteristic of the species (4,9).…”

mentioning

confidence: 99%

Multidrug resistance in Candida albicans: disruption of the BENr gene

Martin¹,

Teff²,

Schmidt³

et al. 1995

The BENr gene of Candida albicans, which confers resistance on susceptible strains of Saccharomyces cerevisiae to six structurally and functionally unrelated drugs, was described recently (R. Ben-Yaacov, S. Knoller, G. Caldwell, J. M. Becker, and Y. Koltin, Antimicrob. Agents Chemother. 38:648-652, 1994). This gene bears similarity to membrane proteins encoding antibiotic resistance in prokaryotes and eukaryotes. The effect of disruption of this gene on viability and drug susceptibility was determined. The results indicate that the gene is not essential but its inactivation leads to susceptibility to three of the four drugs tested. Inactivation of this gene did not increase the susceptibility of the mutant to benomyl, suggesting that C. albicans has other mechanisms of resistance, some of which may be additional efflux pumps that confer resistance to this tubulin-destabilizing agent.