Optimizing Antimicrobial Therapy by Integrating Multi-Omics With Pharmacokinetic/Pharmacodynamic Models and Precision Dosing

Abstract

In the era of "Bad Bugs, No Drugs," optimizing antibiotic therapy against multi-drug resistant (MDR) pathogens is crucial. Mathematical modelling has been employed to further optimize dosing regimens. These models include mechanism-based PK/PD models, systems-based models, quantitative systems pharmacology (QSP) and population PK models. Quantitative systems pharmacology has significant potential in precision antimicrobial chemotherapy in the clinic. Population PK models have been employed in model-informed precision dosing (MIPD). Several antibiotics require close monitoring and dose adjustments in order to ensure optimal outcomes in patients with infectious diseases. Success or failure of antibiotic therapy is dependent on the patient, antibiotic and bacterium. For some drugs, treatment responses vary greatly between individuals due to genotype and disease characteristics. Thus, for these drugs, tailored dosing is required for successful therapy. With antibiotics, inappropriate dosing such as insufficient dosing may put patients at risk of therapeutic failure which could lead to mortality. Conversely, doses that are too high could lead to toxicities. Hence, precision dosing which customizes doses to individual patients is crucial for antibiotics especially those with a narrow therapeutic index. In this review, we discuss the various strategies in optimizing antimicrobial therapy to address the challenges in the management of infectious diseases and delivering personalized therapy.

Keywords: antimicrobial therapy; mechanism-based PK/PD models; multi-omics; pharmacokinetic/pharmacodynamic (PK/PD); precision dosing; systems pharmacology.