Phan, Thang (2019) Molecular approach to early diagnosis of colonizing or invasive Candida in critically ill ventilated patients. Doctoral Thesis.
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Candida colonization is a frequent event in respiratory tract of non-immunocompromised intensive care unit (ICU) ventilated patients. From 5 to 30% of Candida colonization 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 of Candida and bacteria species in lower respiratory tract in the central of Vietnam, and to discriminate invasive or colonizing Candida by 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 were C. albicans (42%), C. tropicalis (37%) and C. glabrata (16%). The fluconazole resistance of Candida species 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) were A. baumannii (43.2%), K. pneumoniae (28.4%) and S. aureus (14.8%), with high levels of antimicrobial resistance. A. baumannii showed resistance to all cephalosporin 2, 3, 4 generation (100%) and carbapenem (94%). A 50% of K. pneumoniae was carbapenem-resistant while 100% S. aureus was resistant to methicillin.
To discriminate invasive or colonizing Candida, we chose 2 proteins, ECE1, present in C. albicans and C. dubliniensis, and HWP1, present in almost Candida species, selecting specific epitopes to develop indirect ELISA. ELISA results showed that 47.4% of patients with C. albicans had IC and 28.9% had invasive C. albicans pneumonia. In 19.23% of patients with Candida species had IC and 2.56% had invasive Candida species pneumonia. 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 to C. albicans and C. dubliniensis. A correlation between the ELISA results and 4 clinical parameters (Candida score, 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 all Candida species.
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