Authors:

Tyler S Dierckman

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About Paper:

Nontuberculous Mycobacteria (NTM) are found throughout the environment, but in immunocompromised individuals, they can cause severe infections requiring antibiotic treatment for a year or more. Treatment regimens for many NTM strains are not well standardized and rely on expert opinion rather than empirical data. Our research integrates pharmacokinetic (PK) modeling with established pharmacodynamic (PD) metrics to predict the efficacies of antibiotics in humans against a variety of NTM strains. Tigecycline is one such antibiotic which has shown promise against NTM strains such as M. abscessus in vitro. Prior studies are reviewed to obtain experimentally determined PK parameters including clearance rate constants and volumes of distribution. These parameters, along with dosing, administration route, and mechanism of action, inform the mathematical implementation of the PK model which is solved in MATLAB. The PK model is implemented with random variability to simulate many possible tigecycline concentration time courses that inform efficacy through direct comparison to established therapeutic targets. The percentage of time courses that reach or surpass a therapeutic target is known as the probability of target attainment (PTA). PTAs are calculated and analyzed against corresponding metrics that represent the concentrations of tigecycline necessary to kill different NTMs to determine tigecycline's efficacy against the spectrum of NTM species. Future work includes combining PK models to evaluate the effectiveness of multi-antibiotic treatment strategies to more accurately represent real treatment situations. More complex and detailed PK-PD models may also be implemented, paving the way for comprehensive human clinical studies of proposed antibiotics against NTMs. Keywords: Nontuberculous Mycobacteria; Pharmacokinetics; Tigecycline

Source:

Purdue University / 2024

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Co-authors:

Tyler S Dierckman