Precision Antibiotic Dosing in Renal Impairment: Integrating PK-PD Strategies

Antibiotic dosing in renal impairment demands a precision-based approach to maximise efficacy while minimising toxicity. This review synthesises current evidence and practical strategies for optimising antimicrobial therapy across the spectrum of renal dysfunction, including acute kidney injury (AKI), acute kidney disease (AKD), chronic kidney disease (CKD), and end-stage renal disease (ESRD) on renal replacement therapy (RRT). We describe phase-specific considerations in AKI - oliguric, anuric, diuretic, and recovery phases and highlight the transitional AKD period, where dosing often aligns with CKD principles but requires dynamic reassessment. Limitations of estimated glomerular filtration rate (eGFR) equations are discussed, including the role of gold-standard measures such as inulin clearance and 24-hour creatinine clearance in special populations. Pharmacokinetic/pharmacodynamic (PK/PD) integration serves as the cornerstone of dose optimisation, with emphasis on maintaining time-dependent and concentration-dependent targets despite fluctuating renal function. Model-informed precision dosing (MIPD) platforms and emerging biosensor technologies capable of real-time drug and biomarker monitoring (e.g., NGAL) are explored as tools for individualised therapy. The role of therapeutic drug monitoring (TDM) is underscored for agents with a narrow therapeutic window. Dialysis-specific strategies are detailed for intermittent haemodialysis (IHD), peritoneal dialysis (PD), and continuous renal replacement therapy (CRRT), summarising commonly used antibiotic regimens. This review proposes an integrated framework that combines PK/PD principles, AKI phase-specific dosing, dose adjustments in dialysis, and precision tools to guide antimicrobial therapy in renal impairment, enabling safer and more effective treatment in this complex patient population.