Effect of Fluconazole on Aspergillus Infection Associated with Chronic Granulomatous Disease

Abstract

Aspergillus infection is the most frequent fungal infection associated with chronic granulomatous disease (CGD), and often results in a life-threatening situation. This report describes the use of high-dose fluconazole, a new antifungal agent, for invasive Aspergillus infection in a patient with CGD. A 27-month-old boy was sent to our hospital because of unknown fever in October, 1988. He was then admitted for pneumonia and pleural effusion of the right lung in February, 1989. Treatment with antibiotics was ineffective, and cultures of throat and pleural fluid were negative. In May, 1989, Aspergillus fumigatus was cultured from a subcutaneous abscess at the point of pleural puncture. Therefore we speculated that Aspergillus might have been the cause of pneumonia. The patient was diagnosed as having CGD by NBT test. Treatment with miconazole, flucitocin and amphotericin-B syrup was ineffective. From July, 1989, he was given 100 mg/day fluconazole d.i.v., but the drug did not reach an effective serum concentration to combat Aspergillus. However, an effective concentration of fluconazole was reached at a dose of 250 mg/day, and the chest X-ray findings subsequently improved, despite occasional high fever and continued high CRP. In July, 1990, the route of fluconazole administration was changed from d.i.v. to p.o. at the same dose, resulting in a serum concentration of fluconazole higher than that achieved with d.i.v. treatment. Both the clinical and laboratory findings showed improvement thereafter. Therapy for Aspergillus infection associated with CGD was found to necessitate high doses of anti-fungal drugs over a long period, although treatment with previously employed anti-fungal drugs could not be continued due to their adverse side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Disseminated aspergillosis due to Aspergillus flavus in an experimental model: efficacy of azole therapy

“…Based on these findings, it would be tempting to suggest a possible role for fluconazole in disseminated aspergillosis, either as prophylaxis in patients at risk, or in early disseminated lesions, but the available clinical evidence has to be carefully assessed. Administration of fluconazole (250 mg day −1 ) resulted in clinical and radiological improvement in aspergillosis complicating chronic granulomatous disease, where treatment with miconazole, flucytosine and amphotericin B had been ineffective 48 . Similarly, Mizuguchi et al.…”

“…Administration of fluconazole (250 mg day )1 ) resulted in clinical and radiological improvement in aspergillosis complicating chronic granulomatous disease, where treatment with miconazole, flucytosine and amphotericin B had been ineffective. 48 Similarly, Mizuguchi et al 49 found fluconazole to be effective in therapy of a patient with semi-invasive aspergillosis, while van Burik et al 28 described a patient with cutaneous aspergillosis in whom no new lesions developed while the patient was receiving fluconazole (200 mg day )1 ). In contrast, Kujath and Lerch 50 reported that Aspergillus infections of multiple soft tissue injuries did not improve with fluconazole therapy.…”