Person:

Rhee, Chanu

Abstract Background: Procalcitonin (PCT)-guided antibiotic therapy has been shown to reduce antibiotic use in critically ill patients with suspected or proven infection, but its impact on mortality remains uncertain. Our meta-analysis examines the effect of PCT-guided antibiotic therapy on survival in critically ill patients. Methods: We searched PubMed, the Cochrane Library, Scopus, Web of Science, EMBASE and clinicaltrials.gov electronic databases up to October 2016. The meta-analysis was restricted to randomized controlled trials (RCTs) of critically ill patients receiving PCT-guided antibiotic treatment and reporting survival or antibiotic duration. Study quality was assessed using the Cochrane risk of bias tool. Two reviewers conducted all review stages independently, and a third reviewer adjudicated any differences. Data was pooled using random-effects meta-analysis. Results: Of the 18 RCTs selected (n = 5,183 patients; Table), 17 assessed mortality and 11 assessed antibiotic duration; 8 scored ≥3 and 10 scored ≤2 out of 6 on the risk of bias assessment. Compared with controls, PCT-guided antibiotic treatment was associated with a significant reduction in mortality (20.7% vs. 23.0%; risk ratio [RR] 0.90[95% CI, 0.81–0.99], I2=0%; Figure 1). Survival benefit was retained in the RCT subset with a lower risk of bias (score ≥ 3; RR 0.87 [95% CI, 0.77,0.98], I2=0%; Figure 2) but not with higher risk (score ≤ 2; RR 0.98 [95% CI, 0.80–1.20], I2=0%). Our analysis of the effect of PCT-guided antibiotic therapy on antibiotic duration displayed significant heterogeneity (I2=61.2%, P = 0.004), which precluded reporting on aggregate effect. Important limitations were: single center RCT (n = 9), lack of double blinding (all studies) and variable protocol non-adherence and timeframes examined for mortality. Conclusion: In a meta-analysis of RCTs of critically ill patients with suspected or proven infection, PCT-guided antibiotic treatment was associated with a significant reduction in mortality. The observed survival benefit was weighted towards RCTs of relatively higher quality. However, the plausibility of this finding, as well as the impact of protocol non-adherence on outcome needs further study. Funded by Intramural NIH and NCI Contract# HHSN261200800001E Disclosures All authors: No reported disclosures.

Abstract Background: Discordance between in vitro susceptibility and empiric antibiotic therapy is inextricably linked to antibiotic resistance and decreased survival in bloodstream infections (BSI). However, its prevalence, patient- and hospital-level risk factors, and impact on outcome in a large cohort and across different pathogens remain unclear. Methods: We examined in vitro susceptibility interpretations for bacterial BSI and corresponding antibiotic therapy among inpatient encounters across 156 hospitals from 2000 to 2014 in the Cerner Healthfacts database. Discordance was defined as nonsusceptibility to initial therapy administered from 2 days before pathogen isolation to 1 day before final susceptibility reporting. Discordance prevalence was compared across taxa; risk factors and its association with in-hospital mortality were evaluated by logistic regression. Adjusted odds ratios (aOR) were estimated for pathogen-, patient- and facility-level factors. Results: Of 33,161 unique encounters with BSIs, 4,219 (13%) at 123 hospitals met criteria for discordant antibiotic therapy, ranging from 3% for pneumococci to 55% for E. faecium. Discordance was higher in recent years (2010–2014 vs. 2005–2009) and was associated with older age, lower baseline SOFA score, urinary (vs. abdominal) source and hospital-onset BSI, as well as ≥500-bed, Midwestern, non-teaching, and rural hospitals. Discordant antibiotic therapy increased the risk of death [aOR = 1.3 [95% CI 1.1–1.4]). Among Gram-negative taxa, discordant therapy increased risk of mortality associated with Enterobacteriaceae (aOR = 1.3 [1.0–1.6]) and non-fermenters (aOR = 1.7 [1.1–2.5]). Among Gram-positive taxa, risk of mortality from discordant therapy was significantly higher for S. aureus (aOR = 1.3 [1.1–1.6]) but unchanged for streptococcal or enterococcal BSIs. Conclusion: The prevalence of discordant antibiotic therapy displayed extensive taxon-level variability and was associated with patient and institutional factors. Discordance detrimentally impacted survival in Gram-negative and S. aureus BSIs. Understanding reasons behind observed differences in discordance risk and their impact on outcomes could inform stewardship efforts and guidelines for empiric therapy in sepsis. Disclosures All authors: No reported disclosures.