Safety of Antibacterial Agents in Liver Transplantation: A Review of Pharmacokinetic and Pharmacodynamic Aspects

INTRODUCTION. Alterations in hepatic and renal function, systemic inflammation, and immunosuppressive therapy in liver transplant recipients significantly modify the pharmacokinetic and pharmacodynamic profiles of antibacterial agents, necessitating optimization of their dosing strategies.

AIM. To systematize the available evidence on the pharmacokinetic and pharmacodynamic characteristics and drug–drug interaction potential of antibacterial agents in patients after liver transplantation in order to clarify the safety profile of antibacterial therapy.

DISCUSSION. The literature analysis demonstrated that the incidence of infectious complications after liver transplantation reaches 41.3%, with up to 21.7% of cases being caused by multidrug-resistant strains. In the early posttransplant period, changes in the volume of distribution, plasma protein binding, and clearance of antibacterial agents determine the variability of systemic exposure and hinder the attainment of pharmacokinetic and pharmacodynamic targets, increasing the risk of treatment failure and drug toxicity. Clinically significant drug–drug interactions between macrolides (clarithromycin, erythromycin) and calcineurin inhibitors (tacrolimus, cyclosporine) as well as inhibitors of the mechanistic target of rapamycin (mTOR) (sirolimus, everolimus) are associated with increased concentrations of immunosuppressants and an increased risk of toxic reactions. The principal adverse reactions are hepatotoxicity, nephrotoxicity, and hematologic and neurologic complications, the risk of which increases with polypharmacy and impaired renal function.

CONCLUSIONS. The pharmacokinetic and pharmacodynamic variability of antibacterial agents in liver transplant recipients necessitates a personalized approach. The use of therapeutic drug monitoring of β-lactam antibiotics, vancomycin, aminoglycosides, and linezolid, along with the consideration of drug–drug interactions, can improve the efficacy and safety of antibacterial therapy in patients after liver transplantation.

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