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

## TL;DR

This study found that doxycycline combined with other antibiotics did not significantly reduce treatment failure in most gram-positive joint infections, but showed potential benefits for Staphylococcus aureus cases.

## Contribution

The study uses causal inference to evaluate doxycycline's role in PJI treatment, identifying potential benefits in specific subgroups.

## Key findings

- Doxycycline was not significantly associated with treatment failure in overall gram-positive PJI.
- Subgroup analyses suggested a 23%–35% reduction in treatment failure for Staphylococcus aureus infections.
- Benefits were also observed in patients without fever and those with both S. aureus and no fever.

## Abstract

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.

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.

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 < .001), 25%–28% in patients without fever (P < .001), and 34%–35% when both conditions were present (P < .001).

Doxycycline in combination with other antibiotics was not associated with 12-month treatment failure in PJI caused by Staphylococcus, Corynebacterium, or Cutibacterium, with potential benefits in S. aureus infection warranting confirmation in prospective studies.

Doxycycline was not associated with overall treatment failure in gram-positive PJI, and subgroup analyses suggested reduced failure in Staphylococcus aureus infections, highlighting potential benefits that require confirmation in prospective studies.