CORR Insights®: Synovial Cell Count Before Reimplantation Can Predict the Outcome of Patients with Periprosthetic Knee Infections Undergoing Two-stage Exchange

Periprosthetic joint infection (PJI) is one of the most common reasons for revision knee arthroplasty in the United States [¹⁵], it accounts for half of revisions within the first 2 years [⁸], and more than one-quarter of patients treated for PJI go on to recurrence [⁴]. Some variability exists regarding treatment strategies, combinations of treatment modalities, and the relative timing of these interventions. Although failure rates remain high overall, two-stage reimplantation with a course of antibiotics between stages has the greatest rate of success [^{4, 10}]. Many surgeons use a two-week period of antibiotic cessation (“antibiotic holiday”) prior to the second stage procedure during which a variety of tests and examinations can be used to infer whether the infection has been controlled [¹²]. However, serum inflammatory markers (erythrocyte sedimentation rate and c-reactive protein) [¹⁸] and alpha-defensin [¹³] have been found to be poorly predictive of persistent infection after antibiotic holiday. One study [¹⁶] suggested that joint aspiration for synovial white blood cell count (WBC) and polymorphonuclear (PMN) cell percentage are more useful tests. Another study found that an antibiotic holiday improved the predictive value of WBC and PMN thresholds [¹⁴]. Indeed, the American Academy Orthopaedic Surgeons clinical practice guideline on the diagnosis of PJI supported the routine use of an antibiotic holiday [⁵].

However, recent consensus group meetings have concluded that the need for synovial fluid analysis prior to reimplantation is unclear [¹]. Recent studies have suggested that WBC and PMN after antibiotic holiday are poorly predictive [¹¹], and positive results have been reported when an antibiotic holiday was not observed (“continuous antibiotic therapy”) [⁹]. One study even suggested that continuous antibiotic therapy can reduce the recurrence of PJI in patients undergoing two-stage revision arthroplasty [²]. However, the threshold values for WBC and PMN that predict treatment success of the continuous antibiotic therapy approach have not yet been established.

The current study by Ascione et al. [³] reviewed a cohort of 82 patients who underwent two-stage revision arthroplasty for chronic PJI. At 2 years follow-up, 13% had persistent infection and 87% had been treated successfully. On review, WBCs prior to reimplantation were greater in the persistent infection group compared to patients believed to be free of PJI (1344 cells/uL vs. 471 cells/uL, respectively), and PMN was also greater when compared to patients believed to be free of PJI (61% vs. 36%, respectively). Using an analysis of receiver operating curves, the authors found optimal threshold values of 934 cells/uL (WBC) and 52% (PMN). The authors concluded that patients with synovial fluid values greater than these threshold values would be better served by repeat debridement rather than reimplantation.

These findings are immediately applicable to the common clinical scenario of patients who are on chronic antibiotic suppression or prolonged antibiotic therapy either due to prior failed attempts to eradicate infection or for any other reason. In any two-stage treatment course where an antibiotic holiday is not used, these findings provide some indication of when it may be safe to proceed to the second stage.