Journal Article

Candida in the respiratory tract secretions of critically ill patients and the impact of antifungal treatment: a randomized placebo controlled pilot trial (CANTREAT study)

Williamson, David, Rotstein, Coleman, Jiang, Xuran, Hall, Mark, Albert, Martin, Kanji, Salmaan, Muscedere, John, Heyland, Daren, Lauzier, Francois

2014

Overview

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.

• Publisher: Springer Berlin Heidelberg,Springer,Springer Nature B.V
• Subject: Anesthesiology / Anidulafungin / Antifungal Agents - therapeutic use / Bacterial pneumonia / Bronchoalveolar Lavage Fluid - microbiology / Candida / Candida - isolation & purification / Candidiasis - drug therapy / Candidiasis - microbiology / Care and treatment / Clinical outcomes / Clinical trials / Critical care / Critical Care Medicine / Critical Illness / Double-Blind Method / Emergency Medicine / Female / Hospitals / Humans / Inflammation / Intensive / Intensive care / Male / Medical research / Medicine / Medicine & Public Health / Medicine, Experimental / Middle Aged / Morbidity / Mortality / Nosocomial infections / Original / Pain Medicine / Pediatrics / Pilot Projects / Pneumology/Respiratory System / Pneumonia / Pneumonia, Ventilator-Associated - drug therapy / Pneumonia, Ventilator-Associated - microbiology / Production capacity / Prospective Studies / Respiratory System - metabolism / Ventilators