Probability of target attainment to assess efficacy of Clarithromycin, Ethambutol, and Rifampicin to treat nontuberculosis mycobacterium (NTM) infections

Authors: Trevor Jaan Shoaf, Elsje Pienaar
Affiliations: Purdue University Weldon School of Biomedical Engineering, West Lafayette, IN, USA

Introduction and Rationale: NTMs are environmental bacteria that can grow around medical device implants, or in the blood. Since these bacteria are the same genus as \textit{Mycobacterium tuberculosis} (Mtb), antibiotics that are used to treat Mtb are also used to treat NTM infections. Our research shows how the assumption that antibiotics will work effectively across species in a genus is not always a good methodology for disease treatment.

Materials, Methods, and Approach: Published pharmacokinetic (PK) models were recreated in MATLAB to solve for probability of target attainment (PTA), a measure of how efficacious a drug is against a variety of strains in bacterial species.

Results and Discussion: PTA graphs for Clarithromycin (CLR), Ethambutol (EMB), and Rifampicin (RIF) show why these drugs are used for Mtb infection, and why they should be reconsidered in their use to treat NTM infections.

Conclusion: The PTA outputs show that there should be more work to study which antibiotics are the most effective at treating NTM infection.

Overall Impact: The overall impact of this work is to identify gaps in current NTM treatment approaches and inform development of optimal treatment strategies for NTM infections.

Preprint

Preprint

Probability of target attainment to assess efficacy of Clarithromycin, Ethambutol, and Rifampicin to treat nontuberculosis mycobacterium (NTM) infections

Probability of target attainment to assess efficacy of Clarithromycin, Ethambutol, and Rifampicin to treat nontuberculosis mycobacterium (NTM) infections