Effectiveness of Doxycycline in Combination With Other Antibiotics for Gram-Positive Periprosthetic Joint Infections: A Causal Inference Study

Abstract

Background. Doxycycline is occasionally used as step-down therapy in periprosthetic joint infections (PJI), but evidence supporting its efficacy is limited. This study aimed to estimate the effect of doxycycline on 12-month treatment failure in patients with gram-positive PJI. Methods. Adult patients with hip, knee, or shoulder PJI caused by Staphylococcus, Corynebacterium, or Cutibacterium who underwent surgery between April 2013 and April 2023 at Dijon University Hospital (France) were included. Demographic, clinical, biological, and therapeutic data were collected retrospectively. Treatment failure at 12 months was defined as clinical recurrence, new intraoperative microorganisms, surgical revision for infection, or death. The average treatment effect (ATE) of doxycycline was estimated using causal inference methods. Results. Three hundred and eighty-six patients with PJI (median age 72 years, interquartile range [IQR] = 65–80) were analyzed. Most infections involved the hip (62%) were caused by Staphylococcus aureus (64%) and/or polymicrobial (42%). Doxycycline was prescribed in 19% of patients (n = 72), for a median of 64 days (IQR = 42–84). At 12 months, treatment failure occurred in 35%, without significant difference between exposed and unexposed patients (33% vs 36%, P =.68). Overall, doxycycline was not significantly associated with treatment failure (ATE(IPTW) = −0.09; 95% CI = −0.24 to 0.05; P =.19). Subgroup analyses suggested that doxycycline reduced treatment failure by 23%–26% in S. aureus infections (P