Development of resistance in candida isolates from patients receiving prolonged antifungal therapy

Fan-Havard, Patty; Capano, D.; Smith, Sharon; Mangia, A.; Eng, Robert H. K.

doi:10.1128/aac.35.11.2302

Cited by 135 publications

(69 citation statements)

References 15 publications

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“…However, even with these drugs, protracted treatment is necessary if remission of infection is to be achieved and sustained (Esposito et al, 1990;Leen et al, 1990;Larsen, 1990). The situation has been compounded by an increasing number of reports of azole resistance in oral isolates of Candida species from HIV+ and AIDS patients (Tavitian et al, 1986b;Korting et al, 1988;Warnock et al, 1988;Fox et al, 1991;Kitchen et al, 1991;Fan-Havard et al, 1991).…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…Consequently, they frequently receive antifungal agents such as fluconazole throughout their period of hospitalization. Prolonged exposure to an azole can select strains with diminished susceptibilities (4), and consequently, increasing doses may be necessary. For that reason, clinical laboratories may be asked to monitor the susceptibility of isolates from such patients in order to determine when strains with diminished susceptibility have been selected (3).…”

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confidence: 99%

Quality Control Limits for Fluconazole Disk Susceptibility Tests on Mueller-Hinton Agar with Glucose and Methylene Blue

Barry

Billé²,

Brown

et al. 2003

J Clin Microbiol

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An international collaborative study was performed in order to propose quality control limits for fluconazole disk diffusion susceptibility tests on Mueller-Hinton agar with 2% glucose and 0.5 g of methylene blue per ml. The supplements may be added before autoclaving the agar, or Mueller-Hinton agar plates may be flooded with a glucose-methylene blue solution. Replicate tests on both types of agar plates generated data to propose zone size limits for tests of Candida parapsilosis ATCC 22019 (22 to 33 mm), C. tropicalis ATCC 750 (26 to 37 mm), and C. albicans ATCC 90028 (28 to 39 mm). C. krusei ATCC 6258 was not useful for this purpose.Immunocompromised patients are often colonized by or infected with fungi, especially Candida spp. Consequently, they frequently receive antifungal agents such as fluconazole throughout their period of hospitalization. Prolonged exposure to an azole can select strains with diminished susceptibilities (4), and consequently, increasing doses may be necessary. For that reason, clinical laboratories may be asked to monitor the susceptibility of isolates from such patients in order to determine when strains with diminished susceptibility have been selected (3). For many laboratories, the disk diffusion procedure may be the most practical method for this purpose. A standardized method and well-defined quality control procedures are essential in order to determine when significant changes are being observed over an extended period of time.In 1996, we proposed a disk diffusion procedure that was performed on RPMI 1640 broth with 2% glucose and 1.5% agar (1). Subsequent studies were carried out to find an agar medium that should be readily available in most clinical laboratories. Mueller-Hinton (MH) agar could be used for this purpose, but it had to be supplemented with 2% glucose in order to increase the number of clinical isolates that would grow adequately. Unfortunately, the added glucose resulted in a significant amount of growth within zones of inhibition and zone edges that were not well defined. Addition of a low concentration of methylene blue (0.5 g/ml) made the zones of inhibition clearer and easier to measure precisely (2,8).Plates with MH-glucose-methylene blue (GMB) agar can be prepared in advance and stored until needed, but the shelf life of such plates has not been determined. Prepared agar plates are practical for surveys, when the number of tests can be predicted in advance and prolonged storage of the plates is not necessary. An alternative approach is preferred for clinical laboratories where susceptibility tests are only sporadically needed. Fresh MH agar plates are commonly available in clinical laboratories, and they can be supplemented by flooding the surface with a GMB solution.Flooding procedure. A stock solution of methylene blue (5 mg/ml) was prepared and refrigerated at 2 to 8°C. To 100 ml of a 40% glucose solution, 200 l of the stock methylene blue was added to give 10 g of methylene blue per ml of 40% glucose (GMB solution). The GMB solution was dispensed int...

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“…Primary infections are essentially due to Candida albicans. After antifungal treatments, relapses are common and are often due to Candida glabrata (also known as Torulopsis glabrata) (2,7,18). Furthermore, the use of antifungal azoles seems to enhance the development of such mycoses (8,15).…”

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confidence: 99%

Genetic Structure ofCandida glabrataPopulations in AIDS and Non-AIDS Patients

Meeûs

Renaud

Mouveroux³

et al. 2002

J Clin Microbiol

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Analysis of the population genetics structure of natural populations elucidates the functioning and evolutionary capabilities of natural populations. It is particularly appropriate for organisms that cannot be directly observed (37). Indeed, the genotypic structure can provide useful clues for estimating the reproductive mode, gene flow, geographical structure, and approximate sizes of reproductive units (10).Infectious diseases involve organisms whose population biology is difficult to assess. This is why molecular markers are useful tools in increasing our understanding of their epidemiology (40).Candidoses are cosmopolitan infections due to yeast-like fungi. These yeasts are responsible for severe mucocutaneous or systemic infections, particularly in premature infants, pregnant women (in that case the infection is mildly self-limiting), after invasive intervention, in AIDS and immunodeficient patients (e.g., cancer, graft, and transplantation patients), and during chemotherapy (corticoids or antimitotics) and radiotherapy (26). Oropharyngeal candidosis is the earliest and the most common fungal infection found in AIDS patients (5, 6, 16). Moreover, susceptibility to other mycoses increases with the development of AIDS (17). Primary infections are essentially due to Candida albicans. After antifungal treatments, relapses are common and are often due to Candida glabrata (also known as Torulopsis glabrata) (2,7,18). Furthermore, the use of antifungal azoles seems to enhance the development of such mycoses (8,15).C. glabrata is a commensal yeast commonly isolated from the human digestive tract. This yeast is considered to be haploid and without a sexual cycle (45). Until know, very little attention has been devoted to the genetics of this opportunistic pathogen compared to the related C. albicans (1,3,28,48). Thus, basic information on the biology and epidemiology of C. glabrata is needed.We report here the enzyme polymorphism observed for 33 putative gene loci in 63 C. glabrata strains in 11 reference strains and in 52 strains isolated from hospitalized patients (22 in Paris and 30 in Montpellier). Furthermore, the patterns of 24 RAPD [random(ly) amplified polymorphic DNA] primers from 20 of these strains are compared to the multilocus enzyme electrophoresis (MLEE) results. This allows inferences to be made regarding the genetic structure and reproductive modality displayed by C. glabrata populations with respect to geography, infected organs, and the human immunodeficiency virus (HIV) status of the patient. MATERIALS AND METHODSOrigin of the different strains. We used 11 reference strains. Strain 774 comes from the Centraalbureau voor Schimmelcultures (Delft, The Netherlands), along with the reference CBS 138 T ; strains 918, 949, 957, 960, 962, 965, 970, and 971 were provided by the Institut Pasteur (Paris, France) with reference numbers IP 3, 811,13,20,14,12,32, and 9, respectively, and strains 1109 and 1110 came from SANOFI (Montpellier, France) with reference numbers SANOFI 2223 and 2231.

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Development of resistance in candida isolates from patients receiving prolonged antifungal therapy

Cited by 135 publications

References 15 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

Quality Control Limits for Fluconazole Disk Susceptibility Tests on Mueller-Hinton Agar with Glucose and Methylene Blue

Genetic Structure ofCandida glabrataPopulations in AIDS and Non-AIDS Patients

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