LAUSR

Abstract Background Early identification of patients at high risk of morbidity and mortality following Gram-negative bloodstream infections (GN-BSI) based on initial clinical course may prompt adjustments to optimize diagnostic and treatment plans. This retrospective cohort study aims to develop early clinical failure criteria (ECFC) to predict unfavorable outcomes in patients with GN-BSI. Methods Adults with community-onset GN-BSI who survived hospitalization for at least 96 hours at Palmetto Health hospitals in Columbia, SC, USA from January 1, 2010 to June 30, 2015 were identified. Multivariate logistic regression was used to examine association between clinical variables within 72–96 hours of BSI and unfavorable outcomes (28-day mortality or hospital length of stay >14 days). Results Among 766 patients with GN-BSI, 225 (29%) had unfavorable outcomes. After adjustments for Charlson Comorbidity Index and appropriateness of empirical antimicrobial therapy in multivariate model, predictors of unfavorable outcomes included systolic blood pressure <100 mmHg or vasopressor use (adjusted odds ratio [aOR] 1.8, 95% confidence interval [CI] 1.1–2.5), heart rate >100/minute (aOR 1.7, 95% CI 1.1–2.5), respiratory rate ≥22/minute or mechanical ventilation (aOR 2.1, 95% CI 1.4–3.3), altered mental status (aOR 4.5, 95% CI 2.8–7.1), and peripheral WBC count >12 × 103/mm3 (aOR 2.7, 95% CI 1.8–4.1) at 72–96 hours from index BSI. Area under receiver operating characteristic curve of ECFC model in predicting unfavorable outcomes was 0.77 (0.84 and 0.71 in predicting 28-day mortality and prolonged hospitalization separately, respectively). Predicted 28-day mortality increased from 1% in patients with no ECFC to 3%, 7%, 16%, 32%, and 54% in presence of each additional criterion (P < 0.001). Predicted hospital length of stay was 7.5 days in patients without any ECFC and increased by 4.0 days (95% CI 3.1–4.9, P < 0.001) in presence of each additional criterion. Conclusion Risk of 28-day mortality or prolonged hospitalization can be estimated within 72–96 hours of GN-BSI using ECFC. These criteria may have utility in future clinical research in assessing response to antimicrobial therapy based on a standard evidence-based definition of early clinical failure. Disclosures P. B. Bookstaver, CutisPharma: Scientific Advisor, <$1,000. Melinta Therapeutics: Speaker’s Bureau, <$1,000.