Impact of bronchial colonization with Candida spp. on the risk of bacterial ventilator-associated pneumonia in the ICU: the FUNGIBACT prospective cohort study

• Published in: Intensive care medicine 2019-06, Vol.45 (6), p.834-843
• Main Authors: Timsit, Jean-Francois, Schwebel, Carole, Styfalova, Lenka, Cornet, Muriel, Poirier, Philippe, Forrestier, Christiane, Ruckly, Stéphane, Jacob, Marie-Christine, Souweine, Bertrand
• Format: Article
• Language: English
• Subjects: Adult; Anesthesiology; Bacteria; Bacterial pneumonia; Bacteriology; Bronchi - drug effects; Bronchi - microbiology; Candida; Candida - drug effects; Candida - pathogenicity; Candidiasis - complications; Candidiasis - epidemiology; Candidiasis - physiopathology; Cell number; Cohort analysis; Cohort Studies; Colonization; Critical Care Medicine; Emergency Medicine; Extubation; Failure; Female; France - epidemiology; Histocompatibility antigen HLA; Histocompatibility antigens; HLA histocompatibility antigens; Human health and pathology; Humans; Immune response; Intensive; Intensive care; Intensive Care Units - organization & administration; Intensive Care Units - statistics & numerical data; Leukocytes; Life Sciences; Lymphocytes; Male; Mechanical ventilation; Medicine; Medicine & Public Health; Microbiology and Parasitology; Middle Aged; Monocytes; Multiple organ dysfunction syndrome; Organ Dysfunction Scores; Original; Pain Medicine; Paralysis; Pediatrics; Pneumology/Respiratory System; Pneumonia; Pneumonia, Ventilator-Associated - epidemiology; Pneumonia, Ventilator-Associated - etiology; Pneumonia, Ventilator-Associated - physiopathology; Prospective Studies; Protistology; Respiratory tract; Risk Factors; Sepsis; Simplified Acute Physiology Score; Time dependence; Ventilation; Ventilator-associated pneumonia; Ventilators
• ISSN: 0342-4642; 1432-1238
• DOI: 10.1007/s00134-019-05622-0

Introduction Respiratory tract Candida spp. colonization is associated with more frequent bacterial ventilator-associated pneumonia (VAP). However, this colonization could be causally related to VAP or simply reflect the immune paralysis associated with multiple organ failure. Objective To prospectively evaluate the relationship between Candida spp. colonization and bacterial VAP in mechanically ventilated patients with multiple organ failure. Inclusion Patients receiving mechanical ventilation for > 4 days and presenting multiple organ failure were included. Tracheal colonization with Candida spp. was evaluated at inclusion (day 0, D0) and every 4 days until extubation. Quantitative proximal and tracheal cultures were performed at each VAP episode. Monocyte human leukocyte antigen-DR isotype (mHLA-DR) expression and the ratio of polymononuclear leukocytes to lymphocytes were used to evaluate immunoparalysis at D0 and D7. The relationship between fungal colonization and VAP was modelled using cause-specific models for repeated events with adjustment for time-dependent confounders and immune factors. Results A total of 213 patients, with a median age of 64, simplified acute physiology score II (SAPS II) score 55 and sequential organ failure assessment (SOFA) score 10, mainly admitted for medical reasons ( n  = 197, 92%), were enrolled in 2012–2015. The median ICU stay was 24 days and the mortality rate was 32% (69 cases). Median mHLA-DR was 5916 Ab-bound/cell [3863–8934]; median lymphocyte count, 0.9Giga/L [0.6–1.3]; neutrophil-to-lymphocyte ratio, 10.9 [6.5–19.7]. Overall, 146 cases (68.5 % ) had tracheal colonization with Candida spp. An episode of VAP occurred (either for the first or only time) in 62 (29.1%) cases 5.5 days (median) after D0; a second episode occurred in 12 (5.6%) cases, 15.5 days (median) after D0. After adjustment, bronchial colonization with Candida was not associated with VAP [adjusted cause-specific hazard ratio = 0.98 (0.59–1.65), p  = 0.95]. Conclusion In patients with mechanical ventilation for more than 4 days and multiple organ failure, bronchial colonization with Candida spp. was not associated with VAP, even after adjustment for immune function.