Challenging the concept of uncomplicated candidemia for shorter courses of antifungal therapy

Background A recent proposal introduced criteria to distinguish uncomplicated from complicated candidemia and identify patients who might be candidates for a shortened (7-day) course of antifungal therapy. We evaluated the feasibility and potential impact of this strategy in a real-world cohort. Methods This retrospective study included patients with candidemia at Lausanne University Hospital (2015-2024). We estimated the sample size required for a randomized non-inferiority trial comparing 7 versus 14 days of therapy for episodes with uncomplicated candidemia, and the reduction in antifungal treatment days under a hypothetical 7-day treatment strategy. Results Among 314 episodes of candidemia, 103 (33%) were classified as uncomplicated. Of the 264 (84%) episodes surviving beyond the first 5 days without limitation of care, 30-day mortality was lower in uncomplicated than complicated candidemia (7% versus 20%; P=0.006). Based on a hypothetical randomized non-inferiority trial comparing 7 versus 14 days of antifungal therapy, assuming an expected event rate of 25% and a non-inferiority margin of 7.5%, 1,103 patients would be required. Overall, the 314 episodes received 6,377 days of antifungal therapy (median, 14 days; interquartile range 13-18). A shortened 7-day treatment strategy for uncomplicated candidemia would have reduced antifungal exposure by 799 treatment days, corresponding to a 13% reduction. Conclusions Uncomplicated candidemia accounted for only one third of episodes, and abbreviated therapy would yield a modest reduction in antifungal exposure. The large sample size required and limited stewardship benefit suggest that a randomized trial would be challenging to conduct.