Clinical pharmacology of antimicrobials: towards optimized treatment of infectious diseases in hospitalized patients

Abstract

To optimize the use of antimicrobials, it is crucial to select a dosing regimen that maximizes treatment effectiveness while minimizing the risk of adverse events. The first part of this thesis focuses on the pharmacokinetics and dosing regimens of antimicrobials. This includes evaluating the dosing regimens of Co-trimoxazole in patients with impaired renal function or undergoing continuous renal replacement therapy, and remdesivir dosing in hospitalized COVID-19 patients. Additionally, the use of continuous infusion versus intermittent administration was examined for ceftriaxone in critically ill patients and beta-lactam antibiotics in neonates.

The second part investigates the pharmacodynamics of antimicrobials. Two studies focused on flucloxacillin. The first assessed the incidence of flucloxacillin-induced hypokalemia and identified risk factors for this adverse effect. The second explored a drug-drug interaction between flucloxacillin and posaconazole, leading to reduced posaconazole exposure. The final two chapters examine the effects of remdesivir in COVID-19 patients. One presents a case report of liver injury likely linked to remdesivir use, while the other analyzes the incidence and predictors of rapid clinical recovery following the start of remdesivir therapy.