Targeted antimicrobial regimens for Gram-negative prosthetic joint infections: a prospective multicenter study

Fluoroquinolones (FQs) are considered the most effective antimicrobial treatment for Gram-negative prosthetic joint infection (GN-PJI). Alternatives are needed due to increasing FQ resistance and side effects. We aimed to compare different targeted antimicrobial strategies for GN-PJI managed by debridement, antibiotics, and implant retention (DAIR) or one-stage revision surgery (1SR) and to review the literature of oral treatment options for GN-PJI. In this prospective, multicenter, registry-based study, all consecutive patients with a PJI caused by a Gram-negative microorganism (including mixed infections with Gram-positive microorganisms), managed with DAIR or 1SR from 2015 to 2020, were included. Minimum follow-up was 1 year. Patients underwent targeted therapy with oral FQ, oral cotrimoxazole, or intravenous or oral β-lactams. Survival analysis was performed with use of Kaplan-Meier and Cox proportional hazards models to identify factors potentially associated with treatment failure. Seventy-four patients who received either FQ (n = 47, 64%), cotrimoxazole (n = 13, 18%), or β-lactams (n = 14, 18%) were included. Surgical strategy consisted of DAIR (n = 72) or 1SR (n = 2). Median follow-up was 449 days (interquartile range 89-738 days). Failure free survival did not differ between the FQ (72%) and cotrimoxazole (92%) groups (log rank, P = 0.13). This outcome did not change when excluding all pseudomonal PJI in the FQ group. Cotrimoxazole is a potential effective targeted antimicrobial therapy for patients with GN-PJI. A randomized controlled trial is needed to confirm the findings of this study.