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Purpose As changes in antibiotic therapy are common, intent‐to‐treat and definitive therapy exposure definitions in infectious disease clinical trials and observational studies may not accurately reflect all antibiotics received over the course of the infection. Therefore, we sought to describe changes in antibiotic therapy and unique treatment patterns among patients with bacteremia. Methods: We conducted a retrospective cohort study of hospitalizations from Veterans Affairs (VA) Medical Centers (January 2002‐September 2015) and community hospitals (de‐identified Optum Clinformatics DataMart with matched Premier Hospital data; October 2009‐March 2013). In the VA population, antibiotic exposures were mapped from the culture collection date among those with positive Staphylococcus aureus cultures. In the Optum‐Premier population, exposures were mapped from the admission date among those with a primary diagnosis of bacteremia. Results: Our study included 50 467 bacteremia admissions, with only 14% of admissions having the same treatment pattern as another admission. For every 100 bacteremia admissions, 89 had changes in antibiotic therapy. For every 100 bacteremia admissions with changes in therapy, 95 had unique antibiotic treatment patterns. These findings were consistent in both populations, over time, and among different facilities within study populations. The median time to first therapy change was 2 days after initial therapy, with a median of three changes. Conclusions: Changes in antibiotic therapy for bloodstream infections were nearly universal regardless of hospital setting. Based on our findings, common antibiotic exposure definitions of intent‐to‐treat and definitive therapy would misclassify exposure in 86% of admissions, which highlights the need for better operational definitions of exposure in infectious diseases research. [ABSTRACT FROM AUTHOR]

Study Objective: Current guidelines recommend higher daptomycin doses than the daptomycin label dose of 6 mg/kg for methicillin‐resistant Staphylococcus aureus (MRSA) bacteremia; however, the evidence supporting this recommendation is from in vitro and case series studies. This study evaluated the comparative effectiveness of the daptomycin label dose versus higher daptomycin doses in patients with MRSA bacteremia. Design: Retrospective national cohort study. Setting: Veterans Affairs medical centers. Patients: A total of 371 adults with MRSA bacteremia who were admitted between 2002 and 2015 and treated initially with vancomycin within 24 hours of initial culture collection and then switched to daptomycin therapy within 7 days; 138 patients (37.2%) received daptomycin doses higher than the daptomycin label dose (7 mg/kg or greater), and 233 (62.8%) received the daptomycin label dose (6 mg/kg). Measurements and Main Results: Clinical outcomes were compared among those who received the daptomycin label dose and those who received the higher dose using propensity score–matched Cox proportional hazards regression models. To identify dose partitioning associated with optimal survival, classification and regression tree (CART) analysis was used among patients, controlling for confounding with a 30‐day mortality disease risk score. Propensity score–matched 30‐day mortality was 8.6% (6/70 patients) among the higher dose group versus 18.6% (13/70 patients) among the label dose group (hazard ratio 0.31, 95% confidence interval 0.10–0.94). No significant differences were observed in inpatient mortality, length of stay, 30‐day readmission, or 30‐day S. aureus reinfection between groups. CART analysis resulted in doses of 7 mg/kg or greater providing benefit only among patients with higher (more than 51%) predicted probabilities of 30‐day mortality (p<0.001). Conclusion: To our knowledge, this is the first comparative effectiveness study of daptomycin doses in patients with MRSA bacteremia. Survival benefits were observed with doses higher than the daptomycin label dose (7 mg/kg or greater) for the treatment of MRSA bacteremia. These data suggest that higher doses than the daptomycin label dose may be preferred over the label dose for improving clinical outcomes in patients with MRSA bacteremia. [ABSTRACT FROM AUTHOR]

Background Limited and conflicting data exist evaluating low-bioavailability oral antibiotics (LOW) for definitive treatment of Enterobacteriaceae bacteremia (EB), and existing dogma limits their use. We compared outcomes for EB from a suspected urine source with LOW vs. high-bioavailability oral antibiotics (HIGH). Methods This was a retrospective cohort study across Veterans Affairs hospitals from 2006 to 2015. Inclusion criteria were monomicrobial EB and matching urine culture; receipt of active, empiric parenteral antibiotic(s); and conversion to a single oral LOW or HIGH between treatment day 2 and 6. Exclusion criteria were EB in the previous year, prior urologic abscess, or chronic prostatitis. HIGH included fluoroquinolones or trimethoprim-sulfamethoxazole. LOW included oral β-lactams. The primary outcome was all-cause 30-day mortality or recurrent EB. Patients were weighted using propensity-based overlap weights to make the groups more similar to each other at baseline. Log binomial regression models were used to estimate relative risks and risk differences. Results A total of 4,090 patients met inclusion criteria with 955 LOW and 3,135 HIGH. The median days of parenteral antibiotics before conversion to oral antibiotics were 4 (IQR 3, 5) in LOW and 4 (IQR 3, 4) in HIGH. The composite primary outcome occurred in 42 (4.4%) LOW and 94 (3.0%) HIGH. The adjusted relative risk (aRR) of the composite primary outcome with LOW was 1.28 (95% CI 0.86–1.89; risk difference [RD] 0.9%). Recurrent EB within 30-days occurred in 14 (1.5%) LOW and 12 (0.4%) HIGH (aRR 3.24, 95% CI, 0.46–22.8; RD 1.0%). Thirty-day mortality occurred in 29 (3.0%) LOW and 82 (2.6%) HIGH (aRR 1.0, 95% CI, 0.66–1.52; RD 0%). Similar outcomes were observed at 90 days. Conclusion There was no difference in the composite outcome of 30-day mortality and recurrent bacteremia comparing hospitalized patients who received LOW vs. HIGH for the definitive treatment of EB from a suspected urine source. While there was a nonsignificantly higher risk of 30-day recurrent EB with LOW, the absolute risk and risk difference were small, suggesting that definitive therapy with LOW may be considered. Future evaluation is needed to better understand risk factors for recurrent EB and which patients may fail LOW. Disclosures All Authors: No reported Disclosures. [ABSTRACT FROM AUTHOR]