Orthopedic implant-associated infections (OIAI) are common and challenging complications, leading to increased healthcare costs and impaired quality of life. When implant removal or replacement is not feasible for infection control, chronic suppressive antibiotic therapy (SAT) is indicated as an alternative strategy. However, the effectiveness of SAT remains uncertain, as well as the risks of antimicrobial resistance, adverse effects, and its impact on patients’ quality of life. This study aimed to evaluate the failure rate of SAT after 12 months of follow-up and to identify independent risk factors for failure.

This was a single-center prospective cohort study including patients with OIAI who received SAT and were followed in the musculoskeletal infection outpatient clinic of a specialized university hospital between August 2019 and May 2025. Patients were divided into two groups according to SAT success or failure and matched based on demographic, clinical, microbiological, and surgical variables. Outpatient follow-up was conducted at 3, 6, and 12 months after SAT initiation. Independent risk factors for SAT failure were identified using logistic regression with the stepwise forward method. A significance level of 5% was adopted for all analyses.

Twenty-three out of 59 patients experienced SAT failure, with a mean age of 53.2 years (SD ± 18.5) in the failure group. Prosthetic joint infections showed the highest failure rate (56.3%), followed by spinal arthrodesis-associated infections (50%) and fracture-related infections (28.2%). The mean SAT duration was 38.2 weeks (SD ± 30.1). The most frequently isolated microorganisms in OIAI were S. aureus (n = 24) and coagulase-negative Staphylococcus (n = 9). Gram-negative bacteria were found in 43.7% of failures (RR 1.1; 95% CI 0.5–2.45; p = 0.81), and multidrug-resistant bacteria in 13.6% (RR 1.0; 95% CI 0.38–2.64; p = 1.0). The most commonly used antibiotic regimen was ciprofloxacin plus sulfamethoxazole-trimethoprim (39% in the failure group and 58% in the success group, p = 0.15). Polymicrobial infection was the only independent risk factor for SAT failure (57% vs. 43% in the success group; RR 2.29; 95% CI 1.08–4.85; p < 0.05).

A high rate of SAT failure was identified, and polymicrobial OIAI was independently associated with this unfavorable outcome.