In-vitro susceptibility of Cryptococcus neoformans isolates to fluconazole and itraconazole

Abstract

The in-vitro susceptibilities of 143 isolates of Cryptococcus neoformans, collected from British patients between 1994 and 1996, to fluconazole and itraconazole were compared with those of 36 isolates collected between 1971 and 1985, 41 isolates collected between 1986 and 1989, and 43 Ugandan isolates collected in 1996. Testing was done with a broth microdilution method in YNB medium supplemented with glucose, incubation at 30 degrees C for 72 h, and an endpoint of 50% inhibition. The results showed that the MIC ranges, MIC50s and MIC90s of fluconazole and itraconazole for C. neoformans isolates from the UK have remained unchanged despite the recent widespread use of triazoles for long-term maintenance of patients with AIDS-associated cryptococcal meningitis. The MIC ranges, MIC50s and MIC90s of the 43 isolates from untreated Ugandan patients with AIDS were similar to those of the British isolates. Examination of our records for 1994-96 revealed six cases in which a four-fold or greater rise in the MIC of fluconazole was associated with relapsed cryptococcal meningitis.

Trends in Antifungal Drug Susceptibility of Cryptococcus neoformans Isolates in the United States: 1992 to 1994 and 1996 to 1998

“…Most of the 1994 isolates for which MICs were higher were from patients who had previously received fluconazole. Davey et al (10) (10). Moreover, because the C. neoformans isolates that we tested were collected as part of a populationbased surveillance study, our results may be more representative than those of the British study.…”

“…Various methods have been developed for testing the susceptibility of C. neoformans to azole antifungal agents, including fluconazole and itraconazole (2,10,12,13,21,23). The NCCLS reference method (16) has proved problematic, as has the alternative broth microdilution method (13) described in the M27-A document (21).…”

“…The NCCLS reference method (16) has proved problematic, as has the alternative broth microdilution method (13) described in the M27-A document (21). Nevertheless, regardless of the particular test method used, there is some evidence that elevated MICs of fluconazole are correlated with a diminished response in animal models of cryptococcal meningitis (8,25) and that a high or rising MIC of fluconazole is sometimes associated with treatment failure in human immunodeficiency virus-infected persons with cryptococcosis (1,3,4,7,9,10,17). The distribution of azole antifungal MICs in C. neoformans has been assessed in several prior studies.…”

“…To date, there have been few published reports of the emergence of resistance to amphotericin B, fluconazole, or itraconazole in Cryptococcus neoformans during treatment (3,4,7,9,10,17,20 …”

Prevention of cryptococcosis in HIV‐infected patients with limited access to highly active antiretroviral therapy: evidence for primary azole prophylaxis

“…A study in the UK from 1994 to 1996 found no clinical resistance, although six patients did have at least an 8-fold increase in minimal inhibitory concentrations (MICs) on serial isolates while on treatment. They also found no difference in MIC 50 between isolates from 1994 to 1996 and those from 1971 to 1986 [34]. Data from the USA comparing azole susceptibility in 1992-1994 and 1996-1998 failed to demonstrate an increase in resistance.…”