Abstract Background Complicated intra-abdominal infections (cIAIs) require a combined strategy of source control and antimicrobial therapy. Guidelines recommend initial intravenous (IV) therapy with oral step-down therapy following source control. Due to limited data supporting this strategy, we aimed to evaluate the safety and efficacy of oral step-down antimicrobial therapy in cIAIs after initial IV antimicrobial therapy. Methods This retrospective cohort study included hospitalized patients ≥ 18 years of age diagnosed with a cIAI who received > 7 days of IV therapy during index hospitalization at quaternary hospital from March 2017 to October 2021. Patients were excluded for primary or peritoneal dialysis-related peritonitis, necrotizing pancreatitis, fistulizing inflammatory bowel disease, or upper gastrointestinal tract infection; repeat hospitalization during study period; or transfer from another facility after > 24 hours of care. Patients were assigned into two treatment groups: IV-only or oral step-down therapy. The primary outcome was infection recurrence defined as re-initiation of antimicrobials after a treatment-free period of ≥ 3 days. Secondary outcomes included treatment escalation, repeat source control procedure, treatment-related complications, and all-cause mortality. Results The cohort consisted of 248 patients (199 IV-only and 49 oral step-down). Baseline, infection, and treatment characteristics were similar between groups, except for gender, length of stay, and overall treatment duration (Table 1). Patients receiving IV-only therapy had a shorter median antimicrobial duration than the oral step-down group (13 vs. 23 days; P < 0.001). Infection recurrence occurred in 26 (13.1%) and six (12.2%) patients in the IV-only and oral step-down groups, respectively (P = 0.88). Treatment escalation, repeat source control, and 28-day mortality were similar between groups (Table 1). Oral step-down therapy resulted in more adverse drug events (10.2% vs. 3.0%; P = 0.04). Table 1: Baseline and infection-related characteristics for IV only and oral step-down therapy groups aDefined as: solid organ transplant, hematopoietic stem cell transplant within the last 1 year, long-term high-dose steroids (prednisone >10 mg, or equivalent, for ≥2 weeks), concomitant immunosuppressive medication, or HIV (CD4 count <200 cells/µL) bOther antimicrobials included cephalexin, cefpodoxime, doxycycline, fluconazole, and sulfamethoxazole-trimethoprim cAdverse drug events included dermatologic reactions, gastrointestinal upset, nausea/vomiting, diarrhea, fatigue, thrombocytopenia, and acute kidney injury Conclusion Transition to oral step-down after initial IV antimicrobial therapy may be an alternative strategy for the management of cIAIs; however, larger non-inferiority studies are warranted to confirm the safety and efficacy of this approach. Disclosures James Sanders, PhD, PharmD, Merck & Co., Inc.: Grant/Research Support|Shionogi Inc.: Grant/Research Support Sara Hennessy, M.D., Boston Scientific: Advisor/Consultant Sara Hennessy, M.D., Boston Scientific: Advisor/Consultant.
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