Fluconazole resistant candida in AIDS

Fox, R.; Neal, Kim; Leen, Clifford; Ellis, Mark; Mandal, B K

doi:10.1016/0163-4453(91)91767-r

Cited by 109 publications

(68 citation statements)

References 9 publications

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“…Persistence of oral candidosis in these individuals and relapse following treatment with antifungal drugs is very common (Glatt et al, 1988;Samaranayake & Holmstrup, 1989;Larsen,1990). This is thought to be due to a variety of causes, including the underlying immunodeficiency, poor patient compliance, azole hepatotoxicity, gastrointestinal intolerance and the development of decreased drug susceptibility, and, in the case of the imidazole ketoconazole, poor absorption in the presence 1988; Epstein, 1990;Larsen, 1990;Fox et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Reduced azole susceptibility of oral isolates of Candida albicans from HIV-positive patients and a derivative exhibiting colony morphology variation

Gallagher

Bennett

Henman

et al. 1992

Journal of General Microbiology

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Approximately 50 % (15/28) of a selection of oral isolates of Candida albicuns from separate individuals infected with the human immunodeficiency virus (HIV) exhibited low susceptibility to ketoconazole as determined by hyphal elongation assessment. Nine of these isolates exhibited colony morphology variation or switching at 37 "C, of which six expressed low ketoconazole susceptibility. To determine whether colony morphology variation could give rise to derivatives with reduced azole susceptibility, several high-frequency switching variants of three HIVpatient isolates were recovered and assessed. All but one of the variants expressed similar azole susceptibility profiles to their respective parental strains. However, the C. albicans derivative 132ACR expressed significantly reduced susceptibility to ketoconazole in comparison to its parental strain 132A. In whole cells, on the basis of total growth the switched derivative 132ACR was markedly less susceptible than its parental isolate 132A to ketoconazole at 10 p~. A much smaller difference was observed with fluconazole at 10 PM, with the switched derivative 132ACR exhibiting a threefold lower susceptibility compared with the parental isolate 132A. The incorporation of [14C]acetate in control and azole-treated cells of both organisms was higher for the parental strain. When cell lysates of strain 132A and its derivative 132ACR were incubated with 114C]mevalonic acid and ketoconazole, the IC,, for 14C-label incorporation into 63-4 demethyl sterols was fivefold higher for lysates of the . switched derivative 132ACR compared with those of the parental strain 132A. With fluconazole the IC5,, value for the derivative 132ACR was 25-fold higher than for strain 132A. The 14-sterol demethylase of the switched derivative 132ACR was possibly less sensitive to azole inhibition than that of the enzyme of strain 132A. These studies indicated that colony morphology variation in vifro can generate derivatives with stable, reduced azole susceptibility without prior exposure to azoles.

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Section: Introductionmentioning

confidence: 99%

Reduced azole susceptibility of oral isolates of Candida albicans from HIV-positive patients and a derivative exhibiting colony morphology variation

Gallagher

Bennett

Henman

et al. 1992

Journal of General Microbiology

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“…When this organism is cultured from blood, the rate of mortality has been reported to be between 45 and 100% (6, 30). The increase in the rate of isolation of C. krusei may be due to the use of fluconazole both for prophylaxis and for treatment (1,4,13,25,32). C. krusei is resistant to fluconazole both in the laboratory and when the drug is used therapeutically (2,14).…”

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“…These isolates produced six to nine bands, in contrast to C. krusei strains, which produced three to six bands. The MIC of fluconazole for all of the isolates was at least 12.5 mg/liter, as determined by a broth dilution method.Candida krusei has recently emerged as an important opportunistic pathogen that causes infections, particularly in immunocompromised, critically ill, and human immunodeficiency virus (HIV)-positive patients (1, 4,8,13,15,21). When this organism is cultured from blood, the rate of mortality has been reported to be between 45 and 100% (6, 30).…”

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Karyotyping of Fluconazole-Resistant Yeasts with Phenotype Reported as Candida krusei or Candida inconspicua

Mata-Essayag¹,

Baily²,

Dw³

et al. 1996

International Journal of Systematic Bacteriology

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The yeasts Candida krusei and Candida inconspicua have similar phenotypes, which may make discrimination of these organisms difficult. In this study we determined the karyotypes of 51 isolates of these two yeast species by contour-clamped homogeneous electric field electrophoresis. We found that the 43 isolates that had the C. krusei phenotype had three karyotype-specific characteristics. These isolates produced either two or three bands between 2,000 and 3,000 kb and no band between 1,300 and 2,000 kb, and there was either a single bright band at 1,300 or 1,200 kb or two separate bands at 1,300,1,200, or 1,100 kb. Using this technique, we were able to distinguish 27 different C. krusei types on the basis of band variations. The seven isolates identified as C. inconspicua on the basis of phenotype differed in that they produced at least one band between 1,300 and 2,000 kb. These isolates produced six to nine bands, in contrast to C. krusei strains, which produced three to six bands. The MIC of fluconazole for all of the isolates was at least 12.5 mg/liter, as determined by a broth dilution method.Candida krusei has recently emerged as an important opportunistic pathogen that causes infections, particularly in immunocompromised, critically ill, and human immunodeficiency virus (HIV)-positive patients (1, 4,8,13,15,21). When this organism is cultured from blood, the rate of mortality has been reported to be between 45 and 100% (6, 30). The increase in the rate of isolation of C. krusei may be due to the use of fluconazole both for prophylaxis and for treatment (1,4,13,25,32). C. krusei is resistant to fluconazole both in the laboratory and when the drug is used therapeutically (2,14).Isolates are identified as C. krusei strains on the basis of a set of phenotypic characteristics. These characteristics are sufficiently nondiscriminatory that in a clinical laboratory a member of a similar species, such as Candida inconspicua, could be misidentified as a C. knisei strain. The phenotypic characteristics used to identify C. krusei include colony morphology; the presence of pseudohyphae, true hyphae, and elongate blastoconidia; the absence of chlamydoconidia and germ tubes; surface growth that has the ability to form a climbing film on the sides of glass containers: glucose fermentation; assimilation of glucose, glycerol, DL-lactic acid, succinate, ethanol, and Nacetylglucosamine; lack of assimilation of galactose, L-sorbose, sucrose, D-ribose, L-rhamnose, maltose, cellobiose, trehalose, melibiose, raffinose, melezitose, inulin, starch, D-xylose, L-arabinose, D-arabinose, erythritol, ribitol, D-mannitol, salicin, inositol, lactose, galactitol, and glucosamine; failure to grow when potassium nitrate is the nitrogen source; and growth in a vitamin-free medium (28).C. inconspicua is distinguished from C. krusei by its failure to produce hyphae on corn meal agar, the presence of a primitive pseudomycelium, its inability to ferment glucose and assimilate N-acetylglucosamine, its ability to assimilate glucosamine, and its fai...

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“…No data are available about its in vitro activity against Candida albicans isolates from the oral cavities of human immunodeficiency virus (HIV)-infected patients. In the last few years the development of fluconazole-resistant isolates of C. albicans in these patients has been reported (3,5,11,15,19). The lack of standardized methods for in vitro antifungal susceptibility testing presents difficulties in recognizing isolates with reduced susceptibilities to the antifungal agents (12,13 (210) 567-4076. the oral cavities of HIV-infected patients were used in the study.…”

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In vitro activity of a new antifungal triazole, D0870, against Candida albicans isolates from oral cavities of patients infected with human immunodeficiency virus

Barchiesi

Colombo

McGough

et al. 1994

Antimicrob Agents Chemother

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We investigated the in vitro activity of a new antifuingal triazole, D0870, against 100 Candida albicans isolates from the oral cavities of patients infected with human immunodeficiency virus by using a broth macrodilution method following the recommendations provided by the National Committee for Clinical Laboratory Standards (document M27-P). All (4,8,10,21). No data are available about its in vitro activity against Candida albicans isolates from the oral cavities of human immunodeficiency virus (HIV)-infected patients. In the last few years the development of fluconazole-resistant isolates of C. albicans in these patients has been reported (3,5,11,15,19). The lack of standardized methods for in vitro antifungal susceptibility testing presents difficulties in recognizing isolates with reduced susceptibilities to the antifungal agents (12,13 (210) 567-4076. the oral cavities of HIV-infected patients were used in the study. Each strain represented a unique isolate from a patient. All of the strains were chosen from among C. albicans isolates already tested for fluconazole susceptibility by the NCCLS procedure (9). In order to obtain isolates of C. albicans with different patterns of in vitro susceptibility to fluconazole, we included 50 isolates for which the fluconazole MICs were s4 ,ug/ml, which were considered susceptible (group A), and 50 isolates for which the fluconazole MICs were .8 p,g/ml, which were considered resistant (group B) (Fig. 1). All of the isolates were tested for susceptibility to D0870 in a blind and random fashion by a broth macrodilution method following the recommendations provided by NCCLS (9). Two reference strains, C.

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Fluconazole resistant candida in AIDS

Cited by 109 publications

References 9 publications

Reduced azole susceptibility of oral isolates of Candida albicans from HIV-positive patients and a derivative exhibiting colony morphology variation

Reduced azole susceptibility of oral isolates of Candida albicans from HIV-positive patients and a derivative exhibiting colony morphology variation

Karyotyping of Fluconazole-Resistant Yeasts with Phenotype Reported as Candida krusei or Candida inconspicua

In vitro activity of a new antifungal triazole, D0870, against Candida albicans isolates from oral cavities of patients infected with human immunodeficiency virus

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