Abstract
Candida bloodstream infections, and their increasing antifungal resistance, are a global concern. In this cross-sectional study, we analyzed 2,443 culture-confirmed candidemia cases reported in South Africa during 2012-2017 to assess the effect of previous antifungal exposure on nonsusceptible Candida infection. We classified cases by species resistance profile and patient's antifungal use within 14 days before infection. We found that 48% of cases were caused by nonsusceptible species, and 20% of patients had prior antifungal exposure, mainly to fluconazole. In patients >90 days of age, prior antifungal use was significantly associated with nonsusceptible Candida bloodstream infection (adjusted OR 2.02, 95% CI 1.43-2.87; p<0.001), with species-specific effects. No such association was found in neonates and young infants, for whom hospital transmission appeared more influential. Our findings underscore the need for targeted antifungal stewardship and enhanced infection prevention to mitigate antifungal resistance in South Africa.