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.

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Subsequent Course

Of the 12 who initially responded, only four re­mained free of coccidioidal disease. These patients have been followed for 10, 13, 15, and 18 months. One patient died of a myocardial infarction at the end of successful treatment of his fungal infection. Six of the 11 surviving responders had a relapse nine days to 15 months after treatment was stopped. Only one responder suffered a relapse while still receiving fluconazole. The clinical courses of the patients who had a relapse are summarized briefly.

Patient 3 had longstanding fibrocavitary disease. He previously had responded to amphotericin B, but suffered a relapse. A similar scenario followed treat­ment with ketoconazole. He then responded well to treatment with fluconazole (50 mg/day), with reso­lution of all pulmonary symptoms but minimal im­provement in his roentgenogram. Eight months after fluconazole had been discontinued, the patient devel­oped fever, weight loss, and a productive cough, and С immitis was again recovered from his sputum.

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Clinical response was favorable initially in 12 of 14 patients. The clinical scores of each patient at the beginning and end of treatment are listed in Table 1. The mean score before treatment for the 12 responders was 2.8 ±7; their mean score after treatment was 0.08 ±0.3. Resolution of visible lesions was relatively prompt. These 12 patients took fluconazole for from 5 to 23 months (mean, 13 ± 7).

Two patients had failure of treatment. Patient 6 presented with a four-month course of pneumonia followed by multiple disseminated lesions of the skin, soft tissue, and bones. She was given 50 mg/day for two weeks and then advanced to 100 mg/day. Despite treatment for ten weeks, old lesions continued to enlarge, and she developed new cutaneous lesions.

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Patients were enrolled in this study at the University of California San Diego Medical Center and the VA Medical Center from July 1986 to March 1987. Participation in the study was offered to all known patients who had a diagnosis of coccidioidomycosis proven by culture or histology, and who had persistent pulmonary or disseminated infection. Patients with primary pulmonary coccidi­oidomycosis were excluded. Some patients had previously failed to respond to or reactivated following treatment with amphotericin В or ketoconazole. All patients had either pulmonary infection for more than a year or disseminated disease with cultures positive for С immitis or spherules seen on biopsy in conjunction with serum complement-fixation antibodies against Сimmitis antigens. Patients with immunosuppressive disease, hepatitis, or pregnancy were excluded.

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Treatment of chronic coccidioidomycosis can be difficult. There are only a few effective drugs. The best established drug, amphotericin B, must be administered parenterally and is highly toxic. Mico­nazole was the first imidazole to be tested against Coccidioides immitis. The use of miconazole is limited by the fact that it must be administered parenterally, the carrier solvent is toxic, and since the drug is cleared rapidly, it must be administered several times each day. Ketoconazole was the first orally absorbed azole shown to have activity against С immitis. Ketoconazole is often effective in extrameningeal infection; however, its usefulness is limited by a high rate of recurrence after treatment is discontinued. Attempts to reduce rates of relapse by using higher doses have been frustrated by the occurrence of toxic effects.

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Several therapeutic modalities are currently availa­ble for malignant airway occlusion. These include external beam radiation, laser therapy, and en­dobronchial radiation. To our knowledge, no ran­domized study has evaluated these modalities pro­spectively. Although laser therapy achieves immediate airway recanalization, the duration of response is unlikely to be long, as considerable endobronchial as well as extrabronchial tumor is likely to be left untreated. A recent study suggested that when com­pared with external beam radiation, “faster palliation with fewer side effects is probably achieved with laser therapy,” but no supporting data were presented.

External beam radiation can successfully reverse atelectasis and pneumonitis in 21 to 61 percent of patients. In the largest series reported to date, 23 percent of 330 patients had improvement of atelectasis following external radiation. In a recent study of 57 patients, 21 percent achieved resolution of atelectasis and a clear dose response relationship was discerned. However, at follow-up bronchoscopy, none of 14 pa­tients had clearance of endobronchial tumor. These authors therefore concluded that high doses of external radiation are required for reaeration and despite this, the response rate is poor and complications are frequent.

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Thirty-three patients showed at least a one-level improvement in PS, 17 remained unchanged, and five showed at least a one-level deterioration one month following EBRT (Table 1A). A total of 166 symptoms were present prior to therapy; 131 of these resolved or improved, 20 remained unchanged, and 15 wors­ened (Table 1С). When measured as an average parameter, approximately 70 percent of a patients lifetime was rendered symptom free or symptom improved (Fig 1). Fourteen patients were roentgeno- graphically not assessable because neither pretherapy pulmonary atelectasis nor collapse was present. Of the remaining 41 implants, complete roentgenographic reaeration, as illustrated in Figure 2, was achieved in 18 and partial reaeration in 12, for an overall roent­genographic reaeration rate of 30 of 41 or 73 percent (Table 1B).

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