DNA fingerprinting of serial Candida albicans isolates obtained during itraconazole prophylaxis in patients with AIDS

During a randomized double-blind placebo-controlled study testing the effic acy of itraconazole for prophylaxis of systemic and mucosal fungal infectio ns in patients with acquired immune deficiency syndrome, 298 patients were enrolled with 295 evaluable. Of those, 46 patients were considered prophyla xis failures because of recurrent oral or esophageal candidiasis. Oropharyn geal fungal cultures were taken at the time of suspected thrush or Cannida esophagitis, but not at baseline. All of the Candida spp, isolates were cul tured on CHROMagar Candida medium then identified using API 20 AUX strips. Antifungal susceptibility testing was performed following the National Comm ittee for Clinical Laboratory Standards M-27A guidelines. Sequential isolat es were genotyped using randomly amplified poly morphic DNA, Polymerase cha in reaction fingerprints were generated using two repetitive sequence prime rs, (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 isolat es showing a greater than or equal to4-fold reduction in susceptibility: fo ur of these patients were in the itraconazole prophylaxis arm and one was i n the placebo arm. Three of the five had yeast isolations showing changes i n 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 compon ent of the original population.