Objectives: Patients (pts) with mucosal (esophageal [EC] or oropharyngeal [OPC]) candidiasis or invasive candidiasis (IC) often fail amphotericin B (AmB), lipid amphotericin (L-AmB), or azole Rx. The echinocandin CAS is fungicidal against Candida species & cross-resistance with other antifungals has not been seen. Efficacy has been shown for CAS as a first-line agent for EC & IC; less is known about its role in AmB, L-AmB, & azole failure. Methods: Pts with documented EC, OPC, & IC who were refractory or intolerant of AmB or L-AmB were enrolled in a compassionate use (CU) study. CAS was given IV at 50 mg/d (70-mg loading dose in IC pts). Efficacy was assessed at end of CAS Rx based on pt's clinical (&, in IC, microbiological) response. Results: 37 pts with Candida infections were enrolled (17 with EC, 4 with OPC, & 16 with various forms of IC). 11 of the 17 pts with EC also had OPC. The 16 IC cases included 2 blood infections, 2 peritonitis, 1 kidney abscess, 1 mediastinitis, 3 complicated urinary infections, 3 chronic disseminated (hepatosplenic) infections, & 4 multiple site infections. HIV was the most common (91%) risk factor in pts with EC/OPC; pts with IC commonly had acute leukemia/lymphoma (50%) or diabetes mellitus (31%). Most with EC/OPC (91%) & IC (94%) were refractory to ³1 prior antifungal Rx. Favorable outcomes with CAS included 82% (14/17) of pts with EC, 100% (4/4) of pts with OPC, and 87% (13/15) of pts with IC. 1 IC pt was not considered evaluable for efficacy. Most favorable outcomes to CAS were complete responses: 10 of 14 with EC, 2 of 4 with OPC, & 9 of 13 with IC. CAS was dosed 7 to 101 days (mean 31.4 dys). 1 serious drug-related (DR) adverse event (AE) was noted (thrombocytopenia in an AIDS pt). 3 non-serious DRAEs were noted: phlebitis, increased serum AST, & headache/pruritus in 1 pt each. 1 pt discontinued due to a DRAE (thrombocytopenia). 6 pts (5 EC/OPC, 1 IC) successfully received multiple CAS courses. Conclusion: These data suggest that CAS is effective as salvage therapy in pts with EC/OPC or IC. CAS was generally well tolerated.
Full conference title:
43rd Interscience Conference on Antimicrobial Agents
- ICAAC 43rd