Document 1008
 DOCN  M94A1008
 TI    Itraconazole solution for fluconazole-refractory oropharyngeal
       candidiasis in AIDS: correlation of clinical response with in vitro
       susceptibility.
 DT    9412
 AU    Mahmood W; Hamann-Trou D; Phillips P; Zemcov SJ; Montaner JS; Clarke AM;
       AIDS Research Program, St Paul's Hospital, Vancouver, BC, Canada.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(2):23 (abstract no. 386B). Unique
       Identifier : AIDSLINE ICA10/94371567
 AB    OBJECTIVE: To determine the efficacy of itraconazole solution (ITR-SOL)
       in fluconazole-refractory oropharyngeal candidiasis (FLU-ROC), and to
       correlate clinical response with in vitro susceptibility. METHODS:
       Between 5/93 and 1/94, HIV patients with FLU-ROC were prospectively
       evaluated including: clinical assessment; throat culture; ITR and FLU
       MICs (broth macrodilution) for Candida isolates. Patients were treated
       with ITR-SOL 200 mg daily x 2 wk, then 3x/wk. Disease activity (DA) was
       graded by a scoring system. FLU (at baseline) and ITR (at follow-up)
       serum levels were determined by bioassay. RESULTS: 16 cases (14 male, 2
       female) were treated; all isolates were C. albicans. Patient
       characteristics included: median age 35 yr. (range 26-45); median CD4
       count 10/mm3 (range 0-88); median interval from AIDS diagnosis 23 months
       (range 0-42); and median cumulative prior systemic azole therapy 12
       months (range 3-30). Median peak serum FLU level at baseline was 14 mg/l
       (range 4.7-40). ITR-SOL was generally well tolerated; one patient had
       ITR-related GI upset. Clinical responses (reduction in DA to < 50% of
       baseline) were observed in 10/16 cases (63%), usually within 2 weeks.
       Relapse (DA > or = 50% baseline) was noted in 2 patients at 3-6 months
       of therapy. The median FLU MIC was 64 mg/l (range 8- > 64). The median
       ITR MIC was 1.25 mg/l (range 0.31- > 10). ITR MICs of > 4 mg/l were
       present in 4 cases (3/4 non-responders). Failed ITR-SOL therapy could be
       attributed to azole cross-resistance in 3/6, and possible drug
       interaction in 1/6 cases. CONCLUSION: Itraconazole solution was
       effective in 63% of FLU-ROC. In vitro cross-resistance to ITR (MIC > 4
       mg/l) was documented in 25% of cases, and appeared to account for failed
       therapy in 3 of 6 cases. No cases of FLU-ROC could be attributed to
       inadequate serum FLU levels; whereas all C. albicans isolates
       demonstrated resistance (MIC > 8 mg/l) or borderline resistance to FLU.
 DE    Adult  AIDS-Related Opportunistic Infections/*DRUG THERAPY  Candida
       albicans/DRUG EFFECTS  Candidiasis, Oral/*DRUG THERAPY  Drug Resistance,
       Microbial  Female  Fluconazole/PHARMACOLOGY/THERAPEUTIC USE  Human
       Itraconazole/ADMINISTRATION & DOSAGE/PHARMACOLOGY/*THERAPEUTIC  USE
       Male  Middle Age  Prospective Studies  Solutions  Treatment Outcome
       CLINICAL TRIAL  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).