Delamanid or pretomanid? A Solomonic judgement!
Saskia E Mudde1, Anna M Upton2, Anne Lenaerts3
1Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands.
The Journal of Antimicrobial Chemotherapy
|January 28, 2022
Summary
Novel nitroimidazole drugs delamanid and pretomanid show distinct resistance profiles and comparable preclinical efficacy. Delamanid may offer advantages in reducing Mycobacterium tuberculosis bacterial load at lower concentrations.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Drug-resistant tuberculosis (TB) necessitates new treatments.
- Bedaquiline, delamanid, and pretomanid are recent TB drug approvals.
- Delamanid and pretomanid are nitroimidazole class drugs.
Purpose of the Study:
- To compare delamanid and pretomanid based on preclinical research.
- To identify similarities and differences in their properties and efficacy.
Main Methods:
- Review of preclinical data on compound identification and mechanism of action.
- Analysis of drug resistance, in vitro activity, and in vivo pharmacokinetics.
- Evaluation of preclinical in vivo activity and efficacy.
Main Results:
- Delamanid and pretomanid exhibit unique resistance patterns, with some Mycobacterium tuberculosis isolates resistant to one but not the other.
- In vitro, delamanid demonstrated lower Minimum Inhibitory Concentrations (MICs) and greater bacterial load reduction compared to pretomanid.
- Preclinical in vivo efficacy became comparable when adjusted for equivalent clinical drug exposure.
Conclusions:
- Delamanid and pretomanid may be interchangeable in certain TB treatment regimens.
- While delamanid shows superior in vitro activity, preclinical in vivo efficacy is similar at clinically relevant exposures.
- Preclinical model variability necessitates cautious interpretation of comparative results.
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