Combination of caspofungin and an azole or an amphotericin B formulation in invasive fungal infections.

OBJECTIVES: Combination of caspofungin and another anti-fungal agent raise expectation of improved efficacy in severe fungal infections including failures to first line therapy. METHODS: We assessed the efficacy and safety of a combination therapy including caspofungin in 17 immunosuppressed or postoperative patients progressive despite standard anti-fungal therapy. RESULTS: The infections included aspergillosis (6), invasive candidiasis (9), mucormycosis (1) and Scedosporium pneumonia (1). Infections had failed one to four prior lines of treatment. The anti-fungal agent combined to caspofungin was either an amphotericin B formulation or an azole. There were 12 favourable responses (71%) and five failures. The survival rate at 3 months was 47%. Eleven patients died within 2-533 days. The causes of death included the initial fungal infection (4), relapse of the infection after switching to oral monotherapy (2), breakthrough aspergillosis (1), and the underlying condition (4). Clinical and renal tolerance were good. Significant hepatic abnormalities were recorded in eight (50%) of the 16 patients evaluable for biological tolerance. CONCLUSION: Caspofungin combined with an azole or with amphotericin B may be of interest in the treatment of serious fungal infections after failure of conventional therapy. Close monitoring of hepatic function is required. These approach should be evaluated in prospective trials.