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Published on: October 21, 2010
DNA fingerprinting of serial Candida albicans isolates obtained during itraconazole prophylaxis in patients with AIDS
A M Le Monte1, M Goldman, M L Smedema
1Indiana University School of Medicine, Indianapolis 46202, USA. alemonte@iupui.edu
Abstract:
During a randomized double-blind placebo-controlled study testing the efficacy of itraconazole for prophylaxis of systemic and mucosal fungal infections in patients with acquired immune deficiency syndrome, 298 patients were enrolled with 295 evaluable. Of those, 46 patients were considered prophylaxis failures because of recurrent oral or esophageal candidiasis. Oropharyngeal fungal cultures were taken at the time of suspected thrush or Candida esophagitis, but not at baseline. All of the Candida spp. isolates were cultured on CHROMagar Candida medium then identified using API 20 AUX strips. Antifungal susceptibility testing was performed following the National Committee for Clinical Laboratory Standards M-27A guidelines. Sequential isolates were genotyped using randomly amplified polymorphic DNA. Polymerase chain reaction fingerprints were generated using two repetitive sequence primers, (GGA)7 and (GACA)4. The study group consisted of 23 patients, nine from the itraconazole arm and 14 from the placebo arm, who were prophylaxis failures and had more than two C. albicans isolates. Five of 23 had isolates showing a > or =4-fold reduction in susceptibility; four of these patients were in the itraconazole prophylaxis arm and one was in the placebo arm. Three of the five had yeast isolations showing changes in banding patterns over time. Such changes may indicate genetic changes in the same strain that could be linked to acquired resistance to itraconazole, or acquisition of a new strain, or emergence of a previously minor component of the original population.
Insights
Itraconazole prophylaxis for fungal infections in AIDS patients showed potential acquired resistance. Some Candida albicans isolates from patients on itraconazole exhibited reduced susceptibility and genetic changes over time.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Acquired immune deficiency syndrome (AIDS) patients are susceptible to systemic and mucosal fungal infections.
- Prophylaxis with antifungal agents like itraconazole is crucial for managing these infections.
- Understanding antifungal resistance mechanisms is vital for effective treatment strategies.
Purpose of the Study:
- To evaluate the efficacy of itraconazole for fungal infection prophylaxis in AIDS patients.
- To investigate potential genetic changes and acquired resistance in Candida albicans isolates during prophylaxis.
Main Methods:
- Randomized, double-blind, placebo-controlled study design.
- Oropharyngeal fungal cultures, CHROMagar Candida medium, and API 20 AUX for identification.
- Antifungal susceptibility testing (National Committee for Clinical Laboratory Standards M-27A).
- Randomly amplified polymorphic DNA (RAPD) genotyping using (GGA)7 and (GACA)4 primers.
Main Results:
- 46 of 295 evaluable patients experienced prophylaxis failure due to recurrent candidiasis.
- Five of 23 patients with multiple Candida albicans isolates showed a ≥4-fold reduction in susceptibility.
- Four of these five patients were in the itraconazole arm.
- Three patients exhibited changes in DNA banding patterns over time, suggesting genetic alterations.
Conclusions:
- Recurrent candidiasis in AIDS patients on itraconazole prophylaxis may be associated with acquired resistance.
- Observed genetic changes in Candida albicans isolates warrant further investigation into resistance mechanisms.
- These findings highlight the importance of monitoring antifungal susceptibility and genetic profiles in patients undergoing long-term prophylaxis.
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