Fluconazole resistant candida in AIDS

All Candida albicans isolates in Norwegian microbiological laboratories in 1991 judged clinically important (except vaginal isolates) were collected. The isolates were tested for susceptibility to fluconazole with an agar dilution test and a commercially available agar diffusion test. A total of 212 strains (95%) were susceptible to fluconazole, and MICs for most of the strains (92%) were .1.56 pg/ml. The agar diffusion test using a 15-,Lg tablet and a 48-h incubation period separated resistant from susceptible strains with a wide margin. The only exception was a strain for which the MIC was 6.25 ILg/ml. The difference in zone size between the resistant and the susceptible populations of strains was 11 mm. Accordingly, it appears that the agar diffusion test is an appropriate method for detecting fluconazole resistance. The 12 fluconazole-resistant isolates originated from eight AIDS patients with oral or esophageal Candida infections. Seven of the patients had been given fluconazole for 1 month or more, often as self medication. Four had infections that were clinically resistant to fluconazole; one additional patient responded only when the dose was increased. All isolates recovered from these patients were analyzed by multilocus enzyme electrophoresis. The 12 C. albicans isolates belonged to five electrophoretic types, but three of four patients attending one hospital had isolates belonging to one electrophoretic type. One possible explanation for this finding could be that a nosocomial spread of resistant strains has occurred.

Section: Resultsmentioning

confidence: 99%

Susceptibilities of Norwegian Candida albicans strains to fluconazole: emergence of resistance. The Norwegian Yeast Study Group

Sandven¹,

Bjørneklett²,

Mæland³

1993

“…First, does azole and/or polyene therapy select for changes in the mucosal mycoflora (1,9,16,23,26), such as for the inherently resistant organisms C. krusei and T. glabrata (1,3,8,11,20,22,(29)(30)(31)? Second, does azole therapy induce the development of azole and/or polyene resistance in the mycoflora present during its use (2,4,10,14,23,24,27), or is azole therapy even necessary for resistant C. albicans to be present (5,10)? Finally, what is the effect of drug dosage and length of exposure to azoles on the development of clinical resistance?…”

Section: Resultsmentioning

confidence: 99%

Correlation of in vitro fluconazole resistance of Candida isolates in relation to therapy and symptoms of individuals seropositive for human immunodeficiency virus type 1

Cameron

Schell

Bruch

et al. 1993

152

Yeast strains isolated from the oropharynx of 87 consecutive patients infected with human immunodeficiency virus type 1 were examined for in vitro susceptibility to fluconazole. Candida albicans was isolated from 73 patients. Fifty-one patients had received antifungal therapy in the month preceding the yeast infection. Thirty-two patients had symptomatic oropharyngeal candidiasis. The MICs were correlated with azole use and with clinical symptoms and signs. Although there is overlap between groups, in vitro testing identified a large group of patients for whose yeast isolates the fluconazole MICs were high and who remained symptomatic while receiving azole therapy. This study supports the ability of in vitro testing to predict the clinical outcome of mucosal fungal infections. The study also demonstrates that azole resistance of oropharyngeal yeasts is a common problem in patients infected with human immunodeficiency virus type 1 and that this azole resistance has clinical relevance.

“…showing in vitro resistance to FCZ) (17,18). The clinical failures usually correlate with decreased susceptibility of the isolate to FCZ in vitro (5,18) and are often related to previous treatments with this drug (18,24). Explanations for this phenomenon include the mutation (2,22,27) or the selection of a resistant population (1,2,11,22,27) or local factors (17).…”

mentioning

confidence: 99%

Fluconazole concentrations in saliva from AIDS patients with oropharyngeal candidosis refractory to treatment with fluconazole

García-Hermoso

Dromer

Improvisi

et al. 1995

Fluconazole (FCZ) has been extensively used as a primary therapy for oropharyngeal candidosis in AIDS patients. Clinical resistance to FCZ is now encountered, often related to decreased susceptibility of the isolate in vitro. We wondered if low levels in saliva play a role in the therapeutic failure, especially in patients complaining of dry mouth. Sixteen AIDS patients treated for oropharyngeal candidosis with FCZ were studied. MICs for the isolates were determined. Serum and saliva samples were collected to measure FCZ levels with a bioassay using paper disks loaded with the clinical specimens. We showed that (i) paper disks were convenient for collecting saliva in patients with dry mouth; (ii) levels in saliva depended on the FCZ dosage regimen but did not correlate with the response to therapy; (iii) correlation between concentrations in saliva and serum was poor and independent of clinical response to treatment, other therapies, or decreased salivation; and (iv) levels in saliva were always lower than MICs in patients who failed to respond to treatment. In conclusion, therapeutic failures are more likely to be related to in vitro resistance of the isolate to FCZ or insufficient dosage regimen than to decreased salivary secretion.Oropharyngeal candidosis (OPC) is a common mucosal infection among patients infected by the human immunodeficiency virus, occurring in 11 to 95% of these patients according to the degree of the immune defect (6, 7). Candida albicans is the most frequent opportunistic pathogen, responsible for more than 90% of the infections in this group of patients. However, other Candida species such as Candida tropicalis, Candida krusei, and Candida (Torulopsis) glabrata have emerged as significant pathogens (10, 21).The efficacy of fluconazole (FCZ) as a primary therapy for OPC in immunocompromised patients, especially AIDS patients (8), and even as prophylaxis of recurrent OPC (14), has been demonstrated. The rapid resolution of candidosis under FCZ therapy is probably related to the usual susceptibility of C. albicans to FCZ (3,12). Furthermore, studies have shown that levels in saliva are similar to those in plasma in healthy volunteers (4,12).Despite their usual efficacy, some FCZ treatments are considered to be clinical failures (persistence of clinical lesions despite adequate therapy) or mycological failures (culture of a Candida sp. showing in vitro resistance to FCZ) (17, 18). The clinical failures usually correlate with decreased susceptibility of the isolate to FCZ in vitro (5, 18) and are often related to previous treatments with this drug (18, 24). Explanations for this phenomenon include the mutation (2, 22, 27) or the selection of a resistant population (1,2,11,22,27) or local factors (17). Among these factors, diminution of FCZ concentration in saliva could alter FCZ efficacy. Xerostomia (dry mouth and diminished salivation) can modify the course of OPC not only by augmenting the risk of traumatic lesions of the oral mucosa but also by decreasing salivary constituents important i...