Journal of Antimicrobial Chemotherapy, Vol 40, 517-523, Copyright © 1997 by The British Society for Antimicrobial Chemotherapy
JD Cartledge, J Midgley, M Petrou, D Shanson and BG Gazzard
Azole-resistant HIV-related candidosis is increasingly recognized. We
evaluated two new in-vitro susceptibility tests (the NCCLS proposed MIC
method and Odds' assessment of relative growth in single anti-fungal
concentration) as predictors of the clinical outcome of 66 HIV-positive
patients with oral candidosis, of whom 22 were azole naive, 27 had always
previously responded to azole therapy and 17 had persistent candidosis
unresponsive to 7 days of standard azole therapy. None of the last group
responded to increased daily doses of fluconazole or itraconazole capsules,
though nine responded to itraconazole cyclodextrin solution 200 mg bd for 7
days. Our findings suggest that agreement between the Odds' test and the
MIC method was excellent (96- 98%) and that both could discriminate between
isolates of azole- unresponsive patients and those of azole-responsive
patients. For fluconazole susceptibility an MIC > or = 8 mg/L detected
fluconazole- unresponsive patients with a sensitivity of 94% and
specificity of 100%; Odds' method achieved 100% sensitivity and 100%
specificity using all cut-offs between 77 and 88% relative growth in medium
containing fluconazole (10(-5) M; 3 mg/L). For itraconazole and
ketoconazole agreement between MIC and Odds' method was again excellent
(98% and 96%, respectively) but five azole-unresponsive patients appeared
to have ketoconazole-susceptible organisms as defined by both tests, and
similarly 11 appeared to have itraconazole-susceptible organisms by both
tests despite failing to respond to the capsule formulation of the drug. Of
these 11, eight responded to itraconazole solution; this finding implies
that itraconazole capsule failure might represent poor drug absorption
rather than fungal resistance.
ORIGINAL ARTICLES
Unresponsive HIV-related oro-oesophageal candidosis--an evaluation of two new in-vitro azole susceptibility tests
HIV/GU Medicine Unit, Chelsea & Westminster Hospital, London, UK.
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