190. Outcomes of Early Ceftaroline-based Combination Therapy for Methicillin-resistant Staphylococcus aureus Bacteremia

Abstract Background Monotherapy with vancomycin (VAN) or daptomycin (DAP) remains the guideline-driven standard of care for methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B) despite concerns regarding efficacy. While combination therapy is often utilized as salvage treatment for persistent MRSA-B, growing data suggest a potential benefit of combination therapy with ceftaroline as initial therapy for MRSA-B. In light of these data, we updated practice guidance at our institution for management of MRSA-B in March 2020 to favor initial combination therapy with ceftaroline. Herein, we present an assessment of outcomes of patients with MRSA-B initiated on early combination therapy. Methods This was a single-center, retrospective, cohort study of adult patients admitted to the University of Virginia with MRSA-B between July 1, 2018 and February 28, 2021. Patients were considered to have received combination therapy if they received VAN or DAP plus ceftaroline (CPT) within 5 days of index blood culture, and monotherapy if during that period they received VAN and/or DAP alone. The primary outcome was a composite of persistent bacteremia, 30-day all-cause mortality, and 30-day bacteremia recurrence. Time to microbiological cure and safety outcomes were also assessed. A propensity score-weighted logistic regression was conducted. A post-hoc analysis of the primary composite outcome was performed in which patients were only deemed to have received combination therapy if it was started within 72 hours. Results Of 94 patients included, 57 received monotherapy (55 VAN, 2 DAP) and 37 received combination therapy with CPT (30 VAN, 7 DAP). There was no difference between groups for the primary composite outcome in the primary analysis (OR 2.7, 95% CI 0.95-7.72) or the post-hoc analysis (OR 2.37, 95% CI 0.68-8.22). Time to microbiological cure was not different between groups (mean difference 1.47, 95% CI 0.20-2.74). Safety outcomes were similar. Conclusion In this retrospective study, there was no clear benefit or harm of early initiation of combination therapy for MRSA-B. Additional study of initial combination therapy with ceftaroline is warranted given the small number of subjects in the study presented. Disclosures All Authors: No reported disclosures


Session: P-10. Bacteremia
Background. Monotherapy with vancomycin (VAN) or daptomycin (DAP) remains the guideline-driven standard of care for methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B) despite concerns regarding efficacy. While combination therapy is often utilized as salvage treatment for persistent MRSA-B, growing data suggest a potential benefit of combination therapy with ceftaroline as initial therapy for MRSA-B. In light of these data, we updated practice guidance at our institution for management of MRSA-B in March 2020 to favor initial combination therapy with ceftaroline. Herein, we present an assessment of outcomes of patients with MRSA-B initiated on early combination therapy.
Methods. This was a single-center, retrospective, cohort study of adult patients admitted to the University of Virginia with MRSA-B between July 1, 2018 and February 28, 2021. Patients were considered to have received combination therapy if they received VAN or DAP plus ceftaroline (CPT) within 5 days of index blood culture, and monotherapy if during that period they received VAN and/or DAP alone. The primary outcome was a composite of persistent bacteremia, 30-day allcause mortality, and 30-day bacteremia recurrence. Time to microbiological cure and safety outcomes were also assessed. A propensity score-weighted logistic regression was conducted. A post-hoc analysis of the primary composite outcome was performed in which patients were only deemed to have received combination therapy if it was started within 72 hours.
Conclusion. In this retrospective study, there was no clear benefit or harm of early initiation of combination therapy for MRSA-B. Additional study of initial combination therapy with ceftaroline is warranted given the small number of subjects in the study presented.
Disclosures. All Authors: No reported disclosures Background. Bloodstream infections are traditionally treated with intravenous (IV) antimicrobial therapy, which may increase length of stay and healthcare costs. The purpose of this study is to evaluate if oral antibiotic step-down therapy for non-staphylococcal gram-positive bloodstream infections (GP-BSIs) is non-inferior to IV antibiotics.

Oral Antibiotic Step-Down Therapy for Non-Staphylococcal Gram-Positive Bloodstream Infections
Methods. This single-center, retrospective cohort study included patients with a non-Staphylococcus aureus, non-Staphylococcus lugdunensis GP-BSI from January 2017 to December 2019. Patients were excluded if they fit any of the following criteria: organism identified as contaminant, polymicrobial BSI, recurrent BSI within the past 90 days, or receipt of an effective antibiotic for a duration longer than what is indicated for BSI treatment. Patients were categorized into those who received an IV antibiotic for the total duration of therapy and those who received an oral step-down antibiotic for at least one-third of the treatment course. The primary composite outcome was the incidence of 90-day clinical failure consisting of 90-day all-cause mortality, change in therapy due to inadequate clinical response, and 90-day BSI recurrence. The secondary outcomes included the individual components of the primary composite outcome, line-related complications, and hospital length of stay. Bivariate analysis was conducted to assess for predictors of 90-day clinical failure.
Results. A total of 308 patients were included (oral group, n=94; IV group, n=214). Pitt Bacteremia Scores were low overall, but higher in the IV group (0 vs 1, p=0.045). The oral group had a higher proportion of GP-BSI caused by streptococcal species (76% vs 61%, p< 0.001). The oral group had a lower incidence of 90-day clinical failure and was found to be noninferior to the IV group (9% vs 14%; mean difference -5%, 90% CI -12.7 to 2.6). The IV group had a longer hospital length of stay (4 vs 6 days, p< 0.001), however there were no other significant differences in secondary outcomes. Bivariate analysis found no significant predictors of 90-day clinical failure.
Conclusion. Oral antibiotic step-down therapy was found to be non-inferior to IV antibiotic therapy, and thus may be an alternative option for the treatment of non-staphylococcal GP-BSIs.
Disclosures. All Authors: No reported disclosures Background. Group B Streptococci (GBS) or Streptococcus agalactiae colonize humans genitourinary and gastrointestinal tracts particularly of females. The pathogen is capable of causing invasive disease primarily in infants, pregnant and postpartum women as well as the elderly and patients with comorbidities. There is paucity of studies of the disease with regional differences in prevalence and presentation of invasive blood stream infection (BSI). In this study, we aim to assess prevalence, microbiological characteristics as well as clinical outcomes of invasive GBS disease from all ages groups at Hamad Medical Corporation (HMC), Qatar.

Epidemiology, Microbiological Characteristics and Clinical Outcomes of Invasive Blood Stream Infections of Group B Streptococcal Isolates From Qatar
Methods. A retrospective study was conducted on all patients with microbiologically confirmed GBS bacteraemia between January 2015-March 2019. Demographic, microbiological characteristics as well as clinical data were extracted from hospital information system.