Abstract
Whether Candida within the patient microbiome drives the pathogenesis of Staphylococcus aureus bacteremia, described as microbial hitchhiking, cannot be directly studied. Group-level observations from studies of various decontamination and non-decontamination-based ICU infection prevention interventions and studies without study interventions (observational groups) collectively enable tests of this interaction within causal models. Candidate models of the propensity for Staphylococcus aureus bacteremia to arise with versus without various antibiotic, anti-septic, and antifungal exposures, each identified as singleton exposures, were tested using generalized structural equation modelling (GSEM) techniques with Candida and Staphylococcus aureus colonization appearing as latent variables within the models. Each model was tested by confrontation against blood and respiratory isolate data, obtained from 467 groups within 284 infection prevention studies. Introducing an interaction term between Candida colonization and Staphylococcus aureus colonization substantially improved GSEM model fit. Model-derived coefficients for singular exposure to anti-septic agents (- 1.28; 95% confidence interval; - 2.05 to - 0.5), amphotericin (- 1.49; - 2.3 to - 0.67), and topical antibiotic prophylaxis (TAP; + 0.93; + 0.15 to + 1.71) as direct effects versus Candida colonization were similar in magnitude but contrary in direction. By contrast, the coefficients for singleton exposure to TAP, as with anti-septic agents, versus Staphylococcus colonization were weaker or non-significant. Topical amphotericin would be predicted to halve both candidemia and Staphylococcus aureus bacteremia incidences versus literature derived benchmarks for absolute differences of < 1 percentage point. Using ICU infection prevention data, GSEM modelling validates the postulated interaction between Candida and Staphylococcus colonization facilitating bacteremia.