Purpose: Candida spp. are frequently recovered from endotracheal secretions in critically ill patients suspected of having ventilator-associated pneumonia. Observational studies reported an association with worse clinical outcomes but the effect of antifungal therapy in these patients remains unclear. We designed this pilot study to assess the feasibility of a larger trial and to evaluate inflammatory profiles and clinical outcomes in these patients.
Methods: We conducted a double-blind, placebo-controlled, multicenter pilot randomized trial of antifungal therapy in critically ill patients with a clinical suspicion of ventilator-associated pneumonia with positive airway secretion specimens for Candida spp. We also included an observational group without Candida spp. in their airway secretions. We measured recruitment rate, inflammatory and innate immune function profiles over time, and clinical outcomes.
Results: We recruited 60 patients into the randomized trial and 29 patients into the observational study. Markers of inflammation and all clinical outcomes were comparable between placebo and antifungal treatment group at baseline and over time. At baseline, plasma TNF-α levels were higher in patients with VAP and Candida compared to the observational group (mean ± SD) (21.8 ± 23.1 versus 12.4 ± 9.3 pg/ml, p = 0.02) and these patients had lower innate immune function as evidenced by reduced whole blood ex vivo LPS-induced TNF-α production capacity (854.8 ± 855.2 versus 1,559.4 ± 1,290.6 pg/ml, p = 0.01).
Conclusions: This study does not provide evidence to support a larger trial examining the efficacy of empiric antifungal treatment in patients with a clinical suspicion of ventilator-associated pneumonia and Candida in the endotracheal secretions. The presence of Candida in the lung may be associated with persistent inflammation and immunosuppression.
Trial registration: ClinicalTrials.gov NCT00934934.