Background Ampicillin-ceftriaxone (AC) has emerged as an alternative antibiotic regimen for enterococcal infective endocarditis (EIE) with reduced toxicity compared to ampicillin-gentamicin (AG), but evidence regarding its success in reducing EIE-associated death in the United States is limited. Methods We conducted a retrospective, propensity score-matched cohort analysis of EIE patients treated with AC or AG between 2010 and 2017 at three hospitals in Pittsburgh, Pennsylvania. We assessed all-cause 90-day mortality as the primary outcome, and in-hospital mortality, length of hospital stay, hospital readmissions, adverse events, and relapse of bacteremia as the secondary outcomes. Results A total of 190 patients with EIE (100 treated with AC and 90 with AG) were included. Ninety-day mortality was significantly higher with AC than AG (21% vs 8%, p = 0.02). After propensity score-matching, 56 patients in each group remained for the outcomes analysis. Documented aminoglycoside resistance, presence of annular or aortic abscess, and complete pacemaker removal were the significantly different variables between the two matched cohorts. We observed no statistically significant difference in 90-day mortality between the two treatment groups (11% vs 7%, p = 0.55). Adverse events were more common in patients treated with AG (25 vs 39, p = 0.0091), and more patients in the propensity score-matched AG cohort switched antibiotic regimens than in the AC group (10% vs 49%, p < 0.0001). Conclusions Patients treated with AC demonstrate no significant differences in mortality, treatment failure, or bacteremia relapse compared to AG in a propensity score-matched EIE cohort.

Background The mortality rate for Enterococcus faecalis infective endocarditis (EIE) is high. Ampicillin-ceftriaxone (AC) has emerged as an alternative antibiotic regimen with lower toxicity compared to ampicillin-gentamicin (AG), but evidence regarding its success in reducing EIE-associated mortality in the United States is limited. We retrospectively compared mortality in EIE patients treated with AG versus AC. Methods We conducted a retrospective, propensity score-matched, cohort analysis of EIE patients treated with AG or AC from 2010 to 2017 at three hospitals in Pittsburgh, Pennsylvania. Patients were included in the analysis if they were treated for EIE with either AC or AG as the pathogen-directed antibiotic regimen for at least forty-eight hours. We assessed 90-day mortality as the primary outcome, and in-hospital mortality, length of hospital stay, hospital readmissions, adverse events, and relapse of bacteremia as the secondary outcomes. Results A total of 190 patients with EIE (100 treated with AC and 90 with AG) were included. Ninety-day mortality was significantly higher in the AC group than the AG group (21% vs 8%, p = 0.02). After propensity score-matching, 56 patients in each group remained for the outcomes analysis. We observed similar rates of 90-day mortality (6% vs 4%, p = 0.55), bacteremia relapse (0 patients in both cohorts), treatment failure (0% vs 1%, p = 0.50), and 90-day hospital readmission (24% vs 23%, p = 0.85) in the AC and AG-treated patient cohorts. Adverse events were more common in patients treated with AG, and more patients in the AG cohort switched antibiotic regimens than in the AC group. Conclusion EIE patients treated with AC have similar mortality rates as those treated with AG, while AG is associated with increased toxicity and adverse events. Larger, multi-center studies are still needed to compare the two antibiotic regimens. Disclosures All Authors: No reported disclosures

Background The IDSA recommends against screening for and treating ASB in all patients except for those pregnant or undergoing urologic procedures. Nevertheless, antibiotic treatment of ASB is widespread. We conducted a retrospective analysis of physician practices in diagnosis and management of Escherichia coli (E. coli) ASB in a male Veteran population, and compared outcomes in ASB patients treated or not treated with antibiotics. Methods Patients with an E. coli positive urine culture during an ED visit or inpatient admission from 01/2017 to 12/2017 were screened. Patients admitted to the intensive care unit or diagnosed with a sexually transmitted infection, pyelonephritis, prostatitis, or epididymitis/orchitis were excluded. A total of 163 patients were included. Demographics, clinical comorbidities and severity of illness, and outcomes were compared in ASB patients managed with or without antibiotics. ANOVA and Chi-square or Fisher’s exact tests were utilized for comparing measurements. Results ASB was present in 92/163 patients. The majority (74%) of these patients were given antibiotics. Regardless of qSOFA score or alternate infection, there were no significant differences in outcomes between ASB patients treated or not treated with antibiotics: 3-month mortality (15% vs 21%; p = 0.53), emergence of newly resistant bacterial pathogens (7% vs 13%; p = 0.43), recurrent urinary tract infections (61% vs 50%; p = 0.72), clearance of urinary pathogens (75% vs 58%; p = 0.45), length of hospital stay (7 vs 6 days, p = 0.67). Factors that were predictive of physician treatment of ASB included patient comorbid conditions such as benign prostatic hyperplasia, pyuria, and the absence of hematuria. The incidence of adverse events with antibiotic treatment of ASB was low. Conclusion The rate of antibiotic treatment of E. coli ASB in male veterans is high. Outcomes do not differ among ASB patients managed with or without antibiotics. Future studies examining outcomes in patients prescribed antibiotics for multiple episodes of ASB may yield differences, particularly in emergence of resistant pathogens. Focusing on patients with comorbid conditions who are not critically ill would be a high yield target for provider education to reduce ASB treatment. Disclosures All Authors: No reported disclosures

Enterococcus faecalis is a leading cause of infective endocarditis (IE), especially among older patients with comorbidities. Here we investigated the genomic diversity and antimicrobial susceptibility of 33 contemporary E. faecalis isolates from definite or probable IE cases at the University of Pittsburgh Medical Center (UPMC) between 2018 and 2020. Isolates belonging to two multi-locus sequence types (STs), ST6 and ST179, were isolated from nearly 40% of IE patients. Both of these dominant STs carried known beta-lactam resistance-associated mutations affecting the low-affinity penicillin-binding protein 4 (PBP4). We assessed the ability of ampicillin and ceftriaxone (AC) both alone and in combination to inhibit genetically diverse E. faecalis IE isolates in checkerboard synergy assays and an in vitro one-compartment pharmacokinetic-pharmacodynamic (PK-PD) model of AC treatment. ST6 isolates as well as an isolate with a mutation in the PP2C-type protein phosphatase IreP had higher ceftriaxone MICs compared to other isolates, and showed diminished in vitro synergy of AC. Additionally, both ST6 and ST179 isolates exhibited regrowth after 48 hours of humanized exposures to AC. Overall, we found evidence for diminished in vitro AC activity among E. faecalis IE isolates with PBP4 and IreP mutations. This study highlights the need to evaluate alternate antibiotic combinations in clinical practice against diverse contemporary E. faecalis IE isolates.