Adverse events and tolerability of long-term suppressive antibiotic therapy for periprosthetic joint infection: a prospective cohort study

Abstract. Background: Long-term suppressive antibiotic therapy (SAT) is a management strategy for periprosthetic joint infection (PJI) when eradication is unattainable. However, SAT is often associated with adverse events (AEs) that may impact quality of life. This study aimed to evaluate the prevalence and types of AEs, assess patient-reported tolerability, and identify patient- and antibiotic-related factors associated with AEs during SAT for PJI. Methods: A retrospective analysis of a prospectively established cohort of 30 patients receiving SAT for PJI following DAIR (Debridement, Antibiotics, and Implant Retention) or prosthesis exchange between 2019 and 2022 was conducted at a specialized septic surgery department. SAT was indicated for suboptimal surgery or absence of biofilm-active antibiotics and was administered for ≥6 months. Structured patient interviews and institutional records were used to capture AEs, treatment modifications, SAT discontinuation, infection-related complications, and subjective tolerability. Patients were stratified by sex, age, BMI, and antibiotic agent. Results: The median SAT duration was 55 weeks (interquartile range (IQR): 40–101). Non-serious AEs occurred in 97 % of patients (n=29), predominantly affecting the gastrointestinal tract (n=63), skin (n=35), and nervous system (n=25). Treatment modifications were required in 23 % of patients, most frequently with amoxicillin or cotrimoxazole. SAT discontinuation occurred in one patient (3 %) due to multiple AEs. Four patients (13 %) experienced SAEs related to persistent or recurrent infection rather than antibiotic toxicity. Median subjective tolerability was 8 out of 10 (IQR 6–8); 57 % of patients rated tolerability as “good”, 37 % as “moderate”, and 6 % as “poor”. Conclusion: SAT for PJI is associated with a high prevalence of mild to moderate AEs, but treatment discontinuation is rare. Most patients report acceptable tolerability, and serious antibiotic-related complications are uncommon. Careful patient selection, individualized monitoring, and management of AEs are essential to optimize long-term outcomes.