Vancomycin is frequently administered for treating periprosthetic joint infection (PJI), with serum trough levels routinely monitored to ensure therapeutic adequacy. However, the extent to which measured concentrations actually remain within the desired range during treatment is not well defined. In addition, the frequency of necessary dose modifications and patient characteristics that contribute to subtherapeutic or supratherapeutic levels have not been sufficiently explored. Accordingly, the primary objectives of this study were (1) to evaluate whether serum vancomycin concentrations in PJI patients fall within the recommended therapeutic range, and (2) to determine the number of trough measurements and dose adjustments required during standard treatment. This single-center cohort analysis included 108 patients who underwent surgical management for PJI followed by postoperative intravenous vancomycin therapy. Cases were identified through a local arthroplasty registry, and supplementary clinical data were extracted from electronic health records. The study population consisted of 41% women, with a median age of 71 years (IQR 63–79). Hip infections were predominant (73%). Before vancomycin therapy, 54% of patients had undergone a DAIR (debridement, antibiotics, and implant retention) procedure, and 39% had received vancomycin-enriched bone cement during previous revision surgery. Across 791 trough measurements, only 58.2% were within the therapeutic target range of 15–20 mg/L, while 18.5% were below and 23.4% exceeded it. Overall, 71% of patients required at least one dose adjustment, and the median treatment duration was 8 days. Vancomycin trough levels showed moderate positive correlations with age (Spearman’s rho = 0.35, P < 0.001) and baseline creatinine (Spearman’s rho = 0.34, P < 0.001). No significant difference was observed between patients who received vancomycin-loaded cement and those who did not. A considerable proportion of vancomycin serum levels in PJI patients fall outside the recommended therapeutic window despite guideline-based dosing. Elderly patients and those with impaired renal function appear particularly vulnerable to abnormal concentrations. These findings support consideration of alternative broad-spectrum antibiotics that require less intensive therapeutic drug monitoring.
