Management and outcomes of culture-negative periprosthetic joint infection: a systematic review and meta-analysis

Introduction: Culture-negative periprosthetic joint infection (CN-PJI) remains a major diagnostic and therapeutic challenge because antimicrobial and surgical management are often empirical. Methods: We performed a systematic review and meta-analysis to evaluate treatment strategies and outcomes of CN-PJI. MEDLINE and Scopus were searched through 3 July 2025, and 27 cohort studies including 1399 CN-PJI patients were included. Results: Random-effect meta-analyses showed a pooled treatment success proportion of 83.6 % (95 % CI, 78.2–87.9), a pooled failure proportion of 17.2 % (95 % CI, 12.6–22.9), and a pooled mortality proportion of 2.4 % (95 % CI, 1.3–4.6). Subgroup analyses demonstrated lower success and higher failure with debridement, antibiotics, and implant retention compared with one-stage and two-stage exchange arthroplasty. Hip CN-PJI showed higher reported success than knee CN-PJI. Antimicrobial regimens were highly heterogeneous and were not suitable for pooled analysis. Conclusion: Overall, CN-PJI may have favorable outcomes, particularly with exchange arthroplasty, but prospective studies with standardized definitions and treatment reporting are needed.