Background

• Periprosthetic joint infection (PJI) following hip and knee arthroplasty frequently requires prolonged and often multi-agent antibiotic therapy.
• Although antibiotics are central to both curative and suppressive treatment pathways, most PJI literature emphasizes infection eradication and surgical outcomes, while treatment-related toxicity remains inconsistently characterized.
• This systematic review and meta-analysis aimed to quantify patient-level antibiotic-associated adverse eventsduring PJI management. 

Methods

• A PRISMA-guided systematic review and meta-analysis was performed to identify studies reporting antibiotic-associated complications among patients treated for PJI following hip or knee arthroplasty.
• Adverse-event data were extracted at the patient level by complication category, including renal, hepatic, hematologic, gastrointestinal, infectious, and allergic complications.
• Outcomes that were not reported by an individual study were treated as missing rather than assumed to represent zero events, minimizing artificial underestimation of complication rates.
• A study-defined composite of “any adverse drug event” was included in pooled analysis only when explicitly reported by the original investigators.
• Random-effects proportion meta-analysis was performed separately for renal complications and other reported antibiotic-associated adverse events.
• Renal complications were additionally stratified according to exposure to local antibiotic delivery, including antibiotic spacers, antibiotic-loaded cement, intra-articular or topical antibiotics, and antibiotic-containing sponges, versus systemic-only treatment.
• Thirty-nine studies published from 1998–2024, comprising 4,133 patients, met eligibility criteria.
• Antibiotic exposure varied substantially: intravenous treatment ranged from 2–12 weeks and was most commonly 6 weeks; subsequent oral therapy ranged from 4 weeks to 12 months, while suppressive therapy ranged from 3 months to a mean of 5 years.
• Reported follow-up and adverse-event assessment windows ranged from 7 days to 9 years, reflecting substantial variation in treatment and safety surveillance across studies. 

Results

• Renal complications were the most consistently reported adverse events, evaluated across 34 studies and 3,850 patients.
• The pooled renal complication rate was 10.8% (95% CI, 8.0%–14.4%), with substantial between-study heterogeneity (I²=89%).
• In stratified analyses, pooled renal complication rates were:
  • 14.1% (95% CI, 10.6%–18.6%) in cohorts receiving local/spacer-based antibiotic delivery
  • 7.9% (95% CI, 3.3%–17.8%) in systemic-only cohorts.
    These subgroup estimates should be interpreted cautiously given the substantial heterogeneity and overlapping confidence intervals. 
• Other pooled patient-level adverse-event rates included:
  • Any adverse drug event: 10.7% (95% CI, 7.8%–14.4%)
  • Rash: 4.7% (2.7%–8.0%)
  • C. difficile infection: 3.5% (0.9%–12.6%)
  • Nausea/vomiting: 3.0% (1.6%–5.7%)
  • Allergic reactions: 2.8% (1.2%–6.6%)
  • Hepatic complications: 2.4% (1.1%–5.1%)
  • Hematologic complications: 2.2% (0.9%–5.2%). 

Conclusion

• Antibiotic-associated adverse events during PJI treatment are diverse and clinically relevant, but their definitions and reporting remain highly inconsistent across the literature.
• Renal complications were the most consistently reported toxicity and occurred in approximately 1 in 9 patientsreceiving antibiotic treatment for PJI.
• Rates varied across treatment settings, with numerically higher pooled renal complication rates in cohorts incorporating local/spacer-based antibiotic delivery; however, substantial heterogeneity limits direct comparison.
• Greater standardization of adverse-event definitions, surveillance, and reporting is needed to accurately characterize antibiotic-related harm and better inform the risk-benefit balance of prolonged PJI treatment.