Therapeutic Drug Monitoring-Guided Optimization of Vancomycin Dosing in Critically Ill Patients with MRSA Infections: A Pharmacokinetic-Pharmacodynamic Framework for Nigerian ICUs

Vancomycin remains the cornerstone treatment for MRSA infections in critically ill patients, but suboptimal dosing leading to therapeutic failure or nephrotoxicity is common, particularly in populations where pharmacokinetic variability is high and therapeutic drug monitoring (TDM) infrastructure is limited. The pharmacokinetic-pharmacodynamic (PK-PD) framework for TDM-guided vancomycin optimization has not been developed or validated for Nigerian ICU patient populations. This study established a population PK-PD model for vancomycin in MRSA-infected critically ill adults at ICUs in Lagos, Ibadan, and Abuja, and developed a dosing optimization framework applicable to Nigerian clinical settings. Seventy critically ill patients receiving intravenous vancomycin for confirmed MRSA infections were enrolled. Serial blood samples for vancomycin concentration measurement by HPLC-UV and clinical outcome data were collected. Vancomycin MIC against infecting MRSA strains was determined by broth microdilution. Population PK modelling was performed using NONMEM software, and Monte Carlo simulations were applied to evaluate probability of target attainment (PTA) for the AUC24/MIC target of 400 to 600 mg*h/L recommended by ASHP/IDSA/SIDP guidelines. Results showed significant PK variability explained by creatinine clearance, albumin concentration, and body weight as covariates. Standard dosing regimens (15 mg/kg 12-hourly) achieved PTA above 70 percent only in patients with creatinine clearance 60 to 90 mL/min. An AUC-guided dosing nomogram was developed and validated in a separate patient cohort, achieving PTA of 83 percent. This work constitutes an original population PK-PD contribution for vancomycin in Nigerian ICUs and provides a practical TDM framework for improved MRSA treatment outcomes. Keywords: vancomycin, therapeutic drug monitoring, MRSA, pharmacokinetics, ICU.