Abstract Background The optimal metronidazole dose for the treatment of Bacteroides spp. has not been defined. The purpose of this study was to evaluate the utility of a twice (BID), rather than thrice (TID) daily metronidazole dosing strategy among patients with bacteremia due to Bacteroides spp. Methods Adult, hospitalized patients with bacteremia secondary to Bacteroides spp. between October 2010 and June 2021 were assessed across 11 hospitals. The primary endpoint was clinical failure which was a composite of all-cause 30-day mortality, escalation of antimicrobial therapy, 30-day readmission or recurrence due to an anaerobic infection, positive repeat blood cultures for Bacteroides spp., or failure to resolve leukocytosis or fever. Results 208 patients were included; 68 received metronidazole 500mg BID and 140 patients received metronidazole 500mg TID (Figure). Patient age, Charlson comorbidity index, and Pitt Bacteremia score were similar among patients receiving BID vs TID dosing (Table 1). On balance, patients who received BID dosing were more likely to receive oral metronidazole and had shorter lengths of hospitalization prior to bacteremia. Overall, there was no significant difference between rates of clinical failure or other outcomes between patients who received BID versus TID metronidazole dosing (Table 2). In the multivariate model, neither the use of TID dosing (OR = 0.74; 95% CI = 0.33–1.65; P=0.457), time to treatment initiation (OR = 1; 95% CI = 0.81–1.22; P=0.968), days of initial non-metronidazole anaerobic therapy (OR = 0.91; 95% CI = 0.59–1.34; P=0.646), pre-infection length of stay (OR = 1.02; 95% CI = 0.99–1.05; P=0.106), admission prior to 2016 (OR = 1.09; 95% CI = 0.49–2.39; P=0.829), or initial oral metronidazole use (OR = 0.45; 95% CI = 0.18–1.03; P=0.066) were significantly associated with clinical failure. Figure 1:Inclusion and exclusion Non-metronidazole anaerobic coverage consisted of a beta-lactam/beta-lactamase inhibitor, cefoxitin, or a carbapenem Table 1:Demographics and baseline characteristicsTable 2:Clinical outcomes*Patients were considered to have escalated antimicrobial therapy if, in the setting of ongoing signs of infections, antimicrobial therapy was either broadened or the frequency of metronidazole was increased from twice daily to thrice daily. Conclusion In the largest study to date of patients with Bacteroides spp. bacteremia treated with metronidazole, there was no significant difference between BID and TID metronidazole dosing strategies. In the absence of a clear benefit, metronidazole 500mg BID is a reasonable dosing strategy in lieu 500mg TID for infections due to Bacteroides spp. Disclosures Ryan K. Shields, PharmD, MS, Infectious Disease Connect: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Roche: Grant/Research Support.