Clinical Outcomes of Ceftriaxone vs Penicillin G for Complicated Viridans Group Streptococci Bacteremia

BACKGROUND: Ceftriaxone (CTX) and penicillin G (PCN G) are considered reasonable treatment options for viridans group streptococci (VGS) bloodstream infections, but comparisons between these agents are limited. We evaluated clinical outcomes among patients treated with these agents for complicated VGS bacteremia. METHODS: This was a single-center retrospective study of adult patients with ≥1 positive VGS blood culture who were treated with either CTX or PCN G/ampicillin (both included in the PCN arm) between January 2013 and June 2019. The primary outcome was a composite of safety end points, including hospital readmission due to VGS bacteremia or adverse events (AEs) from therapy, Clostridioides difficile infections, treatment modification or discontinuation due to AEs from therapy, and development of extended-spectrum beta-lactamase resistance. Secondary outcomes included individual safety end points, VGS bacteremia recurrence, hospital readmission, and all-cause mortality. RESULTS: Of 328 patients screened, 94 met eligibility criteria (CTX n = 64, PCN n = 30). Streptococcus mitis was the most common isolate, and infective endocarditis was the predominant source of infection. CTX was not significantly associated with increased risk of the primary composite safety outcome (CTX 14% vs PCN 27%; P = .139). The driver of the composite outcome was hospital readmission due to VGS bacteremia or therapy complications. No secondary end points differed significantly between groups. On multivariate analysis, source removal was a protective factor of the primary composite safety outcome. CONCLUSIONS: Despite potential safety concerns with the prolonged use of CTX in complicated VGS bacteremia, this study did not demonstrate higher rates of treatment failure, adverse events, or resistance.