COMPARATIVE OUTCOMES IN ENTEROCOCCUS PROSTHETIC JOINT INFECTIONS FOLLOWING TOTAL JOINT ARTHROPLASTY: AMPICILLIN MONOTHERAPY VERSUS AMPICILLIN-CEFTRIAXONE

Introduction & Aim Prosthetic joint infection (PJI) is a concerning complication following total joint arthroplasty (TJA), contributing to morbidity and healthcare burden. Enterococcus is a challenging pathogen due to intrinsic resistance mechanisms and biofilm formation. While ampicillin-ceftriaxone combination therapy has demonstrated efficacy in enterococcal endocarditis and avoids aminoglycoside toxicity, its role in PJI remains poorly defined. This study aimed to compare revision risk and clinical outcomes in patients with enterococcal PJI treated with ampicillin monotherapy versus ampicillin-ceftriaxone combination therapy. Methods A retrospective cohort study was conducted using the TriNetX database. Patients who underwent debridement, antibiotics, and implant retention (DAIR) for enterococcal PJI following TJA were identified using CPT and ICD-10 codes in conjunction with microbiologic data. Patients were stratified into ampicillin monotherapy and ampicillin-ceftriaxone cohorts. One-to-one propensity score matching was performed, adjusting for demographic and clinical characteristics. Outcomes were assessed at 365 and 730 days. The primary outcome was revision surgery, and secondary outcomes included readmission, adverse drug events, and emergency department (ED) visits. Results A total of 68 patients in the ampicillin monotherapy cohort and 136 in the ampicillin-ceftriaxone cohort were identified. After matching, 55 patients per group remained at 365 days and 47 per group at 730 days. At 365-days, there were no significant differences in revision rates (38.18% vs 36.36%; RR 1.05, 95% CI 0.65-1.71; p =0.84), readmissions (61.82% vs 67.27%; RR 0.92, 95% CI 0.70-1.21; p = 0.55), and adverse drug events (43.63% vs 38.18%; RR 1.14, 95% CI 0.73-1.79; p=0.56). ED visits were significantly lower with ampicillin monotherapy compared to combination therapy (25.46% vs 43.63%; RR 0.58, 95% CI 0.34-1.00; p=0.045), with improved ED-free survival on Kaplan–Meier analysis (log-rank p=0.038). At 730 days, revision rates remained comparable (40.43% vs 53.19%; RR 0.76, 95% CI 0.49-1.18; p=0.21), as did readmissions (70.21% vs 72.34%; RR 0.97, 95% CI 0.75-1.26, p=0.82) and adverse drug events (46.81% vs 38.30%; RR 1.22, 95% CI 0.76-1.96; p=0.40). ED utilization remained significantly lower in the monotherapy cohort (27.66% vs 51.06%; RR 0.54, 95% CI 0.32-0.93; p=0.02), with sustained improvement in ED-free survival (p=0.039) Conclusion Ampicillin monotherapy demonstrated comparable revision rates and safety outcomes compared to ampicillin-ceftriaxone combination therapy in enterococcal PJI following DAIR. Ampicillin monotherapy was associated with significantly lower emergency department utilization at one- and two-year follow-up. These findings suggest that combination therapy may not confer additional clinical benefits in DAIR-managed infections and may be associated with increased healthcare utilization.