Combination and sequential antifungal therapy for XXXX : review of published in vitro and in vivo interactions and 6281 clinical cases from 1966 to 2001.

@entity1 @entity1331 @entity2379 @entity4895 @entity3 @entity1215 @entity5074 @entity2059
The development of newer antifungal drugs is creating new potential combination therapies to combat the dismal mortality rate associated with @entity3 ( @entity3 ). The efficacy of combination therapy for @entity3 has not been established; sparse data on combination or sequential antifungal therapy depict interactions ranging from synergy to antagonism. We reviewed data from all published in vitro studies, animal model studies, and clinical reports and recent abstracts on combination and sequential antifungal therapy for @entity3 from 1966-2001. Among cases of @entity3 during 1966-2001, 249 were treated with 23 different antifungal combinations. @entity2379 plus @entity4895 was the most commonly used (49% of cases), followed by @entity2379 plus @entity2059 (16%) or plus @entity1215 (11%). Combination therapy resulted in improvement in 63% of @entity1 , generally with @entity2379 plus @entity4895 or @entity1215 and indifference with @entity2379 plus @entity2059 . In 27 in vitro reports, we found synergy (in 36% of reports), additivity (in 24%), indifference (in 28%), and antagonism (in 11%). @entity2379 plus @entity4895 and @entity2379 plus @entity1215 showed generally positive interactions and @entity2379 plus @entity2059 showed results that were largely indifferent. Eighteen animal model reports demonstrated synergy (in 14% of reports), additivity (in 20%), indifference (in 51%), and antagonism (in 14%). In general, @entity2379 plus @entity4895 , @entity2379 plus @entity1215 , and @entity2379 plus @entity2059 showed indifferent results, whereas @entity2379 plus @entity1331 showed positive interactions. Thirty-four cases treated during 1990-2001 with sequential therapy, excluding @entity2379 followed by @entity2059 , showed improvement in 68% of cases. Improvement was noted with @entity2379 or @entity2059 followed by @entity5074 but not with @entity2059 followed by @entity2379 .
