RESUMO
BACKGROUND: In critically ill patients, Candida spp. can often be identified in pulmonary samples. The impact of prompt antifungal therapy in these patients is unknown. METHODS: In this retrospective study, 500 adult patients with pulmonary Candida spp. colonization admitted to the intensive care unit (ICU) between 2010 and 2012 were included. The patients were analyzed according to whether or not they received antifungal therapy, which was administered at the discretion of the attending physician. Logistic regression analysis was performed to investigate the impact of antifungal therapy on hospital mortality and new onset of ventilator-associated pneumonia. In a stepwise backward elimination, the impact of age, cancer as an underlying disease, Simplified Acute Physiology Score (SAPS) II, and Sequential Organ Failure Assessment (SOFA) score were considered. RESULTS: After excluding 178 patients with multifocal Candida spp., isolated pulmonary Candida spp. colonization was found in 322 patients (cohort 1). Pre-existing pneumonia was found in 147/322 patients. Out of the remaining 175 patients (cohort 2), 44 patients received any antifungal therapy, and 131 were defined as the control group. Patients who received antifungal therapy had higher hospital mortality (50 vs. 30 %, p = 0.02) and pneumonia rates (47.7 vs. 16.8 %; p < 0.001) than those who did not. In Cox regression analysis, antifungal therapy was not independently associated with favorable outcome (mortality: odds ratio 0.854 (95 % CI 0.467-1.561); new pneumonia: 1.048 (0.536-2.046)), but SAPS II and SOFA score were significantly (p < 0.05) independent covariates for worse outcome. CONCLUSIONS: In critically ill patients with pulmonary Candida spp. colonization, antifungal therapy may not have an impact on the incidence of new pneumonia or in-hospital mortality after adjustment for confounders.
RESUMO
Tick-borne relapsing fever in North America is primarily caused by the spirochete Borrelia hermsii. The pathogen employs multiple strategies, including the acquisition of complement regulators and antigenic variation, to escape innate and humoral immunity. In this study we identified in B. hermsii a novel member of the complement regulator-acquiring surface protein (CRASP) family, designated BhCRASP-1, that binds the complement regulators factor H (FH) and FH-related protein 1 (FHR-1) but not FH-like protein 1 (FHL-1). BhCRASP-1 specifically interacts with the short consensus repeat 20 of FH, thereby maintaining FH-associated cofactor activity for factor I-mediated C3b inactivation. Furthermore, ectopic expression of BhCRASP- 1 converted the serum-sensitive Borrelia burgdorferi B313 strain into an intermediate complement-resistant strain. Finally, we report for the first time that BhCRASP-1 binds plasminogen/plasmin in addition to FH via, however, distinct nonoverlapping domains. The fact that surface-bound plasmin retains its proteolytic activity suggest that the dual binding specificity of BhCRASP-1 for FH and plasminogen/plasmin contributes to both the dissemination/invasion of B. hermsii and its resistance to innate immunity.