Systemic candidiasis

January 2005     View PDF     En español

The problem of anti-fungal resistance

Candidiasis that fails to respond to treatment has been increasingly reported, especially among people who have not benefited from fluconazole and other azole drugs. This is partly due to the widespread, long-term use of azoles for treating and preventing candidiasis. Other factors include treatment with anti-TB drugs, treatment with ciprofloxacin (Cipro) and CD4+ cell counts below 50.

Resistance to azole drugs has often required using amphotericin B. While potent and effective, amphotericin B is toxic, especially to the kidney. Newer versions, such as ABLC, Ambisome and Abelcet, have proven less toxic to the kidneys than the earlier formula. Moreover, a recent study comparing the earlier form to ABLC found that people tolerated ABLC better, which improved their ability to take the drug until the fungal infection successfully cleared. Even among people with some underlying kidney disease, ABLC was better tolerated, resulting in only very small changes in kidney function tests.

Nevertheless, recent studies show that exposure to azole treatment decreases the antifungal activity of amphotericin B. This will likely be the case for newer, less toxic forms of the drug; but more studies need to confirm this. Two other drugs have also been shown to be active against azole-resistant candidiasis. Voriconazole (Vfend) was recently approved in May 2002 and was showed enhanced activity against fluconazole-resistant candidiasis. Based on clinicial trial data, dosage requirements are 200mg twice daily or 3–6mg/kg intraveneously every 12 hours. Another drug called caspofungin acetate (Cancidas) has also shown activity against azole-resistant strains of candidiasis. Recommended dosage is 50mg/day.

There are drug interactions that have been observed including those with anti-HIV drugs, specifically efavirenz (Sustiva), nelfinavir (Viracept) and nevirapine (Viramune). The recommendation is to increase the daily dose to 70mg if a person is taking any of these anti-HIV drugs.

Because of antifungal drug resistance, using drugs to prevent fungal infections is approached with great caution and is generally discouraged. For example, when fluconazole is used to prevent these infections and resistance develops, treating newer and more aggressive infections is difficult and often unsuccessful. So keeping the antifungal drugs for treatment is generally a more desirable approach. Some people with recurrent infections do remain on long-term therapy to prevent them. In this case, however, resistance still remains a concern.