Molecular approach to early diagnosis of colonizing or invasive Candida in critically ill ventilated patients

Candida colonization is a frequent event in respiratory tract of non-immunocompromised intensive care unit (ICU) ventilated patients. From 5 to 30% ofCandidacolonization patients will develop Invasive Candidiasis (IC), which is usually a late-onset ICU acquired infection. Until now, a lot of data highlight the necessity for new IC noninvasive diagnostic in high risk patients. IC is a serious complication in the ICU patients, around 35% mortality and up to 90% in patients with septic shock. How to diagnosis IC early and give appropriate antifungal therapy are the key for a remarkable reduction in mortality. The overall objective of this study was to identify the etiology ofCandidaand bacteria species in lower respiratory tract in the central of Vietnam, and to discriminate invasive or colonizingCandidaby indirect ELISA (Enzyme-linked immunosorbent assay).Ninety six critically ill ventilated patients from 2 hospital in Hue (central Vietnam) were followed in this study. The 3 main isolated fungal pathogens wereC. albicans(42%),C. tropicalis(37%) andC. glabrata(16%). The fluconazole resistance ofCandidaspecies was 21.11% and caspofungin was 4.44%.C. tropicalis, that is becoming a predominant opportunistic in nosocomial fungal infections of ICU in developing country, showed highest fluconazole resistance (34.29%) and caspofungin resistance (5.71%). In ICU, 3 main bacteria resulted in ventilator-associated pneumonia (VAP) wereA. baumannii(43.2%),K. pneumoniae(28.4%) andS. aureus(14.8%), with high levels of antimicrobial resistance.A. baumanniishowed resistance to all cephalosporin 2, 3, 4 generation (100%) and carbapenem (94%). A 50% ofK. pneumoniaewas carbapenem-resistant while 100%S. aureuswas resistant to methicillin.To discriminate invasive or colonizingCandida, we chose 2 proteins, ECE1, present inC. albicansandC. dubliniensis, and HWP1, present in almostCandidaspecies, selecting specific epitopes to develop indirect ELISA. ELISA results showed that 47.4% of patients withC. albicanshad IC and 28.9% had invasiveC. albicans pneumonia. In 19.23% of patients withCandidaspecies had IC and 2.56% had invasiveCandidaspeciespneumonia. The sensitivity and specificity of ECE1 and HWP1 antibody detecting were 80% and 96% and 60% and 77% respectively, indicating the selected ECE1 epitope as a good marker for IC due toC. albicansandC. dubliniensis. A correlation between the ELISA results and 4 clinical parameters (Candidascore, procalcitonin, length of ICU stay, ventilation day) was also investigated, that should help physicians to decide early antifungal therapy waiting for a new IC test that include allCandidaspecies.