Fluconazole in the Treatment of Persistent Coccidioidomycosis: DISCUSSION
Fluconazole is one of the new imidazoles undergoing clinical trials for the treatment of fungal infections. We used fluconazole at a dose of 50 or 100 mg/day for the treatment of patients with persistent or disseminated coccidioidomycosis. Twelve of 14 patients had an initial favorable response, with definite improvement of clinical signs and symptoms of coccidioidal infection; however, five of 11 surviving patients suffered reactivation of their infections 9 days to 15 months after fluconazole was stopped.
Comparison of treatments for coccidioidomycosis is difficult. The disease has many manifestations, and the course is highly variable. Controlled comparisons therefore require large numbers of patients. While this study was not a controlled trial, the criteria used for entry of patients and the results allow us to conclude that fluconazole is active against С immitis. Most patients had a good subjective clinical response. There was also objective evidence of antifungal activity. In five of seven who had follow-up cultures, the cultures became negative. Eight of ten patients who responded clinically and had elevated serologic values prior to treatment had reductions in coccidioidal complement fixation titers. Seven patients’ lesions completely resolved and could not be rebiopsied; however, the changes in chest roentgenograms in five patients with pulmonary involvement were minimal, and the drugs effect was difficult to detect because all but one of these had chronic pulmonary infection in which many of the changes visualized were structural and unlikely to be restored to normal (eg, fibrocavitary lesions).
Long-term cure of chronic or disseminated infection is a difficult goal to achieve in coccidioidomycosis. It was clearly not achieved in this series, despite largely favorable initial results. There was an unacceptably high rate of relapse, even after one to two years of treatment. It is particularly troublesome that a fall in complement fixation titer or a negative fungal culture was noted both in patients who later had a recurrence and in those who did not. Two of the patients who later suffered a relapse had no detectable complement fixation antibody when treatment was stopped. These tests are useful for assessing response to therapy, but neither laboratory “improvement” nor suppression of clinical manifestations necessarily means that the infection is eradicated. Apcalis Oral Jelly
In this series of patients, at doses of 50 or 100 mg/day, fluconazole was well tolerated for extended periods, causing little or no adverse effects reported by the patients. Laboratory evidence of adverse effects was confined to minimal changes in hepatic function in patients who already had some abnormality at the time fluconazole was started. In view of this minimal toxicity and the evidence that fluconazole has substantial antifungal activity, it is recommended that a higher dosage be evaluated.