Fluconazole resistance in Candida in patients with AIDS—A therapeutic approach

Ng, T. T. C.; Denning, David W.

doi:10.1016/0163-4453(93)92707-4

Cited by 72 publications

(38 citation statements)

References 35 publications

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“…glabrata displays a weak susceptibility to fluconazole (8,25,31), leading to many C. glabrata-associated relapses after treatments (46). RFLP typing showed that only specific multilocus genotypes of C. glabrata survive fluconazole treatment (14).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…We have never seen C. albicans isolates for which MICs of other azole drugs are increased in the absence of increased MICs of FZ (Table 2) (32), even for those isolates from AIDS patients treated with KZ only (32), and to our knowledge this has yet to be reported. AIDS patients bearing strains with decreased susceptibilities to FZ only (Table 3) for which the MIC is less than 16.0 g/ml may respond to elevated doses of FZ, KZ, or IZ (7,15,24,32,36), but in our experience most patients will have relapses of infections with isolates highly resistant to FZ and cross-resistant to other azoles (32). Changes in the properties of the cell membranes as a result of greater amounts of nonesterified sterol giving them a phospholipid/sterol ratio that is lower than that of azole-susceptible strains, as reported for C. albicans ATCC 64550 (16,33), could easily explain this cross-resistance (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Patterns of in vitro activity of itraconazole and imidazole antifungal agents against Candida albicans with decreased susceptibility to fluconazole from Spain

Martı́nez-Suárez

Rodríguez-Tudela

1995

Antimicrob Agents Chemother

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Two groups of recent clinical isolates of Candida albicans consisting of 101 isolates for which fluconazole MICs were <0.5 g/ml (n ‫؍‬ 50) and >4.0 g/ml (n ‫؍‬ 51), respectively, were compared for their susceptibilities to fluconazole, clotrimazole, miconazole, ketoconazole, and itraconazole. Susceptibility tests were performed by a photometer-read broth microdilution method with an improved RPMI 1640 medium supplemented with 18 g of glucose per liter (RPMI-2% glucose; J. L. Rodríguez-Tudela and J. V. Martínez-Suárez, Antimicrob. Agents Chemother. 38:45-48, 1994). Preparation of drugs, basal medium, and inocula was done by the recommendations of the National Committee for Clinical Laboratory Standards. The MIC endpoint was calculated objectively from the turbidimetric data read at 24 h as the lowest drug concentration at which growth was just equal to or less than 20% of that in the positive control well (MIC 80%). In vitro susceptibility testing separated azole-susceptible strains from the strains with decreased susceptibilities to azoles if wide ranges of concentrations (20 doubling dilutions) were used for ketoconazole, miconazole, and clotrimazole. By comparison with isolates for which fluconazole MICs were <0.5 g/ml, those isolates for which fluconazole MICs were >4.0 g/ml were in general less susceptible to other azole drugs, but different patterns of decreased susceptibility were found, including uniform increases in the MICs of all azole derivatives, higher MICs of several azoles but not others, and elevated MICs of fluconazole only. On the other hand, decreased susceptibility to any other azole drug was never found among strains for which MICs of fluconazole were lower. Secondary resistance to azole antifungal agents in Candida albicans first appeared in the 1980s in patients with chronic mucocutaneous candidiasis treated with KZ for very long periods of time (25,33,36). The isolates involved had markedly reduced susceptibilities to KZ and cross-resistance to other azole drugs. More recently, resistance to the triazole FZ has been described in C. albicans strains isolated from the oral cavities of AIDS patients in different parts of the world (2, 5-8, 15, 18, 22, 24, 25, 28, 29, 32, 34, 36). The absence in most cases of comparative susceptibility data for alternative azole antifungal agents in these isolates still leaves open the question of whether cross-resistance to azole drugs in C. albicans is a general phenomenon.All of the azole antifungal agents share certain properties that makes in vitro susceptibility testing difficult, mainly partial inhibition of fungal growth that makes MIC endpoint determinations both very difficult and subjective (12,29,35). In the proposed standard of the National Committee for Clinical Laboratory Standards (NCCLS) (23), endpoints for azoles are determined visually at 48 h and the MIC is defined as the lowest drug concentration that reduces growth by 80% relative to the growth of the control (MIC 80%). We have previously shown that increased growth of C. albicans in RP...

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“…Entre estas últimas, se destacaban C. krusei, que es intrínsecamente resistente al fluconazol, y C. glabrata, cuya susceptibilidad a los azoles es muy variable (6)(7)(8). Pero tal vez más notorias fueron las fallas observadas a partir de 1985 en pacientes con sida y mucositis candidiásica bajo tratamiento con fluconazol, quienes desarrollaban candidiasis orofaríngea crónica refractaria a la terapia (9)(10)(11). Esta resistencia fue comprobada por las altas concentraciones inhibitorias mínimas (CIM) de los correspondientes aislamientos (12)(13)(14)(15) …”

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Evaluación de la susceptibilidad de especies de Candida al fluconazol por el método de difusión de disco.

et al. 2003

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Las infecciones causadas por levaduras del género Candida han aumentado en forma dramática en las últimas décadas, especialmente a nivel hospitalario. Paralelamente con este aumento, se ha notado la aparición de resistencia a los antimicóticos, así como la selección de especies diferentes a Candida albicans, todo lo cual ha hecho necesaria la estandarización de pruebas de susceptibilidad in vitro. Entre las varias pruebas disponibles está la de difusión en agar con discos impregnados de antifúngicos, cuya lectura se hace electrónicamente (BIOMIC), lo que proporciona indicaciones objetivas de la concentración inhibitoria mínima (CIM). Se realizó el estudio para determinar la sensibilidad in vitro al fluconazol de 2.139 aislamientos de especies de Candida provenientes de pacientes atendidos en consulta externa o en salas de hospitalización de centros asistenciales en Colombia, Ecuador y Venezuela (región CELA). Candida albicans fue el microorganismo más frecuentemente aislado (62%), seguido a distancia por Candida parapsilosis (11%), Candida tropicalis (8,5 %), Candida glabrata (3,5%) y Candida krusei (2,2%). La CIM demostró que el 88,1% de estos aislamientos eran susceptibles al fluconazol, 5,1% eran susceptibles-dosisdependiente y 6,8% resistentes. El 92,1% de la especie C. albicans fue susceptible mientras que la resistencia al fluconazol fue más notoria en las restantes especies. El BIOMIC es un método rápido y sencillo para la vigilancia epidemiológica de resistencia en levaduras del género Candida recuperadas de pacientes atendidos en centros hospitalarios.Palabras clave: candidiasis, Candida, resistencia anfúngicos, fluconazol, prueba de disco. Resistance to fluconazole by Candida species detected using the disk diffusion method.Infections caused by yeasts belonging to the genus Candida have increased dramatically in the last decades, especially in hospital settings. Concomittantly, antimycotic resistance has emerged, as well as the appearance of non-Candida albicans isolates. To standardize in vitro antifungal susceptibility tests, the agar diffusion test was developed using disks impregnated with the antimycotic compound. Electronic recording of the inhibition zone (BIOMIC), furnishes objective values for the minimal inhibitory concentration (MIC). The fluconazole susceptibility patterns were determined for Candida species isolated from 2.139 patients seen in outpatient clinics or in health-care centers in Colombia, Ecuador and Venezuela. Candida albicans was the species most frequently isolated (62%), followed at a distance by Candida parapsilosis (11%), Candida tropicalis (8.5%), Candida glabata (3.5% ) and Candida krusei (2.2%). MIC determinations showed that 88.1% of these isolates were susceptible to fluconazole, 5.1% were susceptible-dose-dependant and 6.8% resistant. An important proportion (92.1%) of the C. albicans isolates proved susceptible while resistance predominated in the remaining species. These results indicate that the BIOMIC method is rapid and simple, constituting a suitable tool for ...

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Fluconazole resistance in Candida in patients with AIDS—A therapeutic approach

Cited by 72 publications

References 35 publications

Genetic Structure ofCandida glabrataPopulations in AIDS and Non-AIDS Patients

Genetic Structure ofCandida glabrataPopulations in AIDS and Non-AIDS Patients

Patterns of in vitro activity of itraconazole and imidazole antifungal agents against Candida albicans with decreased susceptibility to fluconazole from Spain

Evaluación de la susceptibilidad de especies de Candida al fluconazol por el método de difusión de disco.

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