Combination Antifungal Therapy: Is it for everyone and every mycosis?

A few precepts•To be of value, a combination must be more effective, show reduced toxicity, or cost significantly less than each component.•Statistical significance should support biological significance, i.e. a 10% reduction of morbidity/mortality, even if significant statistically, may not be worth routinely raising the cost of treatment form $100/day to thousands of dollars/day. Alternatively, a marked reduction of mortality/morbidity (e.g. 50%) may be well worth additive costs.•A superior combination might not take hundreds of patients to demonstrate it. On the other hand, too many case series consist of very small numbers insufficiently powered to be conclusive, and (excepting cryptococcosis) almost all are historical series. Case series may prompt randomized controlled trials, but are rarely sufficient in themselves to change medical practice. Randomized controlled trials should be designed to answer the most critical questions, and should have criteria for entry and for outcome evaluation clearly defined in the protocol.