In vitro susceptibility testing of Candida and Aspergillus spp. to voriconazole and other antifungal agents using Etest: results of a French multicentre study.

Minimum inhibitory concentrations (MICs) of the antifungal agent voriconazole were determined using the Etest and compared with those of amphotericin B, itraconazole and fluconazole using 1986 clinical isolates of Candida spp. Voriconazole MICs were also compared with those of amphotericin B and itraconazole using 391 clinical isolates of Aspergillus spp. Voriconazole was found to have more potent activity and lower MIC values than amphotericin B, itraconazole and fluconazole against C. albicans, C. tropicalis, C. parapsilosis and C. kefyr. Against C. glabrata and C. krusei, voriconazole was more active than either of the other two azole antifungals but had similar activity to amphotericin B. For species of Aspergillus, MIC values of voriconazole were lower than those of amphotericin B and itraconazole against A. fumigatus and A. flavus, and were similar to those of amphotericin B against A. niger. Against A. terreus, MIC values for voriconazole and itraconazole were similar. A. terreus is known to be resistant to amphotericin B, and this was reflected in higher MIC values compared with those of voriconazole and itraconazole. Voriconazole therefore compares very favourably with other antifungal agents against a large number of clinical isolates of Candida and Aspergillus spp.

Safety and efficacy of amphotericin B colloidal dispersion. An overview.

The efficacy and safety of Amphotericin B Colloidal Dispersion (ABCD) have been investigated on 572 patients in five Phase I/II clinical trials. The patients were all selected to present a challenging test; having a fungal infection superimposed on severe illness. In 442 cases ABCD was used after amphotericin B, which had been withdrawn. One hundred and forty patients had pre-existing nephrotoxicity. Most patients received doses of 3-6 mg/kg/day of ABCD. Complete or partial recovery was reported in 149/260 (57.3%) patients evaluable for therapeutic response. Patients with Candida infection responded better than those with systemic aspergillosis showing 70.1% recovery vs. 48.8%. ABCD therapy made no difference to serum creatinine levels, even in patients with pre-existing renal failure, nor to liver function as measured by SGOT, alkaline phosphatase and total bilirubin levels in serum. Infusion-related adverse events were the most frequently reported side effects of ABCD. However these studies show clearly that ABCD can be administered safely to patients without the risks of renal toxicity, even when renal toxicity had already developed following therapy with conventional amphotericin B deoxycholate.

Post-traumatic intracranial epidural Aspergillus fumigatus abscess.

We report an intracranial epidural abscess caused by Aspergillus fumigatus in an immunocompetent patient. Infection occurred in a 20-year-old man 2 months after a frontal craniotomy following trauma. The abscess was encapsulated by a thickened dura and although the fungus did not invade the brain, frontal bone was infected and the patient presented with a subcutaneous frontal cellulitis. Initial management combined surgical drainage, resection of necrotic bone and liposomal amphotericin B (1 mg kg-1 per day). After 3 weeks of antifungal treatment a second evaluation surgery was performed. A clinically and radiologically unsuspected new abscess was found and evacuated. Treatment was completed with instillation into the cavity of amphotericin B at a concentration of 5 mg ml-1 and prolonged oral itraconazole (400-600 mg day-1). Treatment was successful and the patient is free of infection after 3 years.