Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study

Rationale Steroid profiles in combination with a corticotropin stimulation test provide information about steroidogenesis and its functional reserves in critically ill patients. Objectives We investigated whether steroid profiles before and after corticotropin stimulation can predict the risk of in-hospital death in sepsis. Methods An exploratory data analysis of a double blind, randomized trial in sepsis (HYPRESS [HYdrocortisone for PRevention of Septic Shock]) was performed. The trial included adult patients with sepsis who were not in shock and were randomly assigned to placebo or hydrocortisone treatment. Corticotropin tests were performed in patients prior to randomization and in healthy subjects. Cortisol and precursors of glucocorticoids (17-OH-progesterone, 11-desoxycortisol) and mineralocorticoids (11-desoxycorticosterone, corticosterone) were analyzed using the multi-analyte stable isotope dilution method (LC–MS/MS). Measurement results from healthy subjects were used to determine reference ranges, and those from placebo patients to predict in-hospital mortality. Measurements and main results Corticotropin tests from 180 patients and 20 volunteers were included. Compared to healthy subjects, patients with sepsis had elevated levels of 11-desoxycorticosterone and 11-desoxycortisol, consistent with activation of both glucocorticoid and mineralocorticoid pathways. After stimulation with corticotropin, the cortisol response was subnormal in 12% and the corticosterone response in 50% of sepsis patients. In placebo patients (n = 90), a corticotropin-stimulated cortisol-to-corticosterone ratio > 32.2 predicted in-hospital mortality (AUC 0.8 CI 0.70–0.88; sensitivity 83%; and specificity 78%). This ratio also predicted risk of shock development and 90-day mortality. Conclusions In this exploratory analysis, we found that in sepsis mineralocorticoid steroidogenesis was more frequently impaired than glucocorticoid steroidogenesis. The corticotropin-stimulated cortisol-to-corticosterone ratio predicts the risk of in-hospital death. Trial registration Clinical trial registered with www.clinicaltrials.gov Identifier: NCT00670254. Registered 1 May 2008, https://clinicaltrials.gov/ct2/show/NCT00670254

PCR based detection of tcdC Delta 117 in Clostridium difficile infection identifies patients at risk for recurrence - A hospital-based prospective observational study

Objectives: Increasing incidence and severity of Clostridium difficile infection (CDI) in the last decades has been attributed to the emergence of hypervirulent C. difficile strain PCR-ribotype 027 (RT027). Commercial multiplex real-time PCR tests allow the presumptive identification of RT027 by detecting a single-base deletion at nt117 in the tcdC gene (tcdC Delta 117). The clinical usefulness of the detection of tcdC Delta 117 is unclear. Therefore, we evaluated test performance and clinical association of the detection of tcdC Delta 117 in patients with CDI in a prospective observational study conducted in a tertiary care hospital in Germany. Methods: From June to October 2015, stool from all patients with suspected CDI was tested for C. difficile according to ESCMID guidelines. C difficile was cultured from positive samples and ribotyping was performed. Clinical data were collected prospectively from all C. difficile positive patients. Results: From 1121 tested stool samples 107 patients with CDI were included in the study. tcdC Delta 117 was detected in 18 (16.8%) of these patients. Multivariable logistic regression analysis revealed an independent association of detection of tcdC Delta 117 with a further episode of CDI (OR 14.6; 95% CI 3.6-58.3: p < 0.001) and death within 30 days of the positive test (OR 5.1; 95% CI 1.0-25.7; p = 0.046). As follow up data are limited, it remains unclear, whether the further episode of CDI was due to tcdC Delta 117 (recurrence) or another type. Conclusion: In our setting, PCR-based detection of tcdC Delta 117 identified patients at risk for recurrent CDI and increased mortality and thus may guide therapeutic choices in CDI patients at the time of diagnosis. (C) 2019 Elsevier Ltd. All rights reserved