Implementing a standard operating procedure is associated with improved vancomycin target attainment in bone and joint infections : a pre-post study

Abstract

Background: Intravenous vancomycin is a mainstay for prosthetic joint infections, osteomyelitis, and implant-associated infections, yet real-world dosing frequently misses PK/PD targets. We assessed whether a ward-embedded standard operating procedure (SOP) improves target attainment and dosing efficiency. Methods: Single-centre, non-randomized pre-post study in an orthopedic service. SOP mandated weight-adapted loading dose, renal function-adjusted maintenance dosing, a 15–20 mg/L trough target, and scheduled TDM. Adults receiving ≥72 h IV vancomycin were included; major renal failure and incomplete TDM were excluded. Pre-SOP data were retrospective; post-SOP data were prospective (03/2024–06/2025). Primary outcome: proportion of troughs within 15–20 mg/L (first and repeated). Repeated measures were modeled with GEE. Time to first in-range trough used Kaplan–Meier (indexed by measurement number). Results: We included 154 patients (pre-SOP n = 58; post-SOP n = 96); baseline characteristics were broadly similar. Use of a weight-based loading dose rose from 31.0% pre-SOP to 100% post-SOP (p < 0.001). At the first trough, 17.2% vs. 26.0% were within 15–20 mg/L (p = 0.238). Across 847 troughs (pre = 319; post = 528), the in-range proportion increased from 28.2% to 41.7%, with subtherapeutic values declining from 38.2% to 26.3% and supratherapeutic values remaining nearly similar (33.5% → 32.0%). Time to first in-range trough shortened from a median of 4 to 2 measurements (log-rank p < 0.001). Post-SOP measurements had higher odds of being in range (aOR 1.68, 95% CI 1.29–2.20; p < 0.001), with marginal predicted probabilities of 33.4% (pre) vs. 47.8% (post). Dose adjustments per patient decreased from a mean 4.0 to 2.48 (p < 0.001). Conclusions: A pragmatic, orthopedic ward–embedded SOP for intravenous vancomycin improved pharmacologic precision: more measurements within target, fewer subtherapeutic exposures, faster target attainment, and fewer dose changes. These data support protocol-first implementation as an immediately actionable step toward more consistent vancomycin exposure in orthopedic care. Future work should integrate AUC-guided, model-informed precision dosing and evaluate clinical endpoints and generalizability across centres.