Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022:3:100128.
doi: 10.1016/j.crphar.2022.100128. Epub 2022 Sep 9.

Pretomanid for tuberculosis treatment: an update for clinical purposes

Sara Occhineri  1   2 , Tommaso Matucci  1   2 , Laura Rindi  3 , Giusy Tiseo  1 , Marco Falcone  1 , Niccolò Riccardi  1   4 , Giorgio Besozzi  4
Affiliations
Review

Pretomanid for tuberculosis treatment: an update for clinical purposes

Sara Occhineri et al. Curr Res Pharmacol Drug Discov. 2022.

Abstract

Coronavirus disease (COVID-19) pandemic determined a 10 years-set back in tuberculosis (TB) control programs. Recent advances in available therapies may help recover the time lost. While Linezolid (LZD) and Bedaquiline (BDQ), previously Group D second line drugs (SLDs) for TB, have been relocated to Group A, other drugs are currently being studied in regimens for drug resistant TB (DR-TB). Among these, Pretomanid (PA), a recently introduced antimycobacterial drug derived from nitroimidazole with both solid bactericidal and bacteriostatic effect, and with an excellent effectiveness and tolerability profile, is in the spotlight. Following promising data obtained from recently published and ongoing randomized controlled trials (RCTs), the World Health Organization (WHO) determined to include PA in its guidelines for the treatment of rifampicin-resistant (RR), multi drug resistant (MDR) and pre-extensively drug resistant TB (pre-XDR-TB) with BDQ, LZD and Moxifloxacine (MFX) in a 6-month regimen. Although further studies on the subject are needed, PA may also represent a treatment option for drug-susceptible TB (DS-TB), latent TB infection (LTBI) and non tuberculous mycobacteria (NTM). This narrative review aims to examine current implementation options and future possibilities for PA in the never-ending fight against TB.

Keywords: DR-TB; Mycobacterium tuberculosis; Pretomanid; Tuberculosis; XDR-TB; preXDR-TB.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
PRISMA flow diagram adapted for our narrative review.
Fig. 2
Fig. 2
Pretomanid chemical structure.
Fig. 3
Fig. 3
Most common adverse events reported during PA administration in combination regimens (Nedelman et al., 2020).
Fig. 4
Fig. 4
Therapeutic algorithm for PA-containing regimens. ∗For LZD dose finding is currently ongoing and therapeutic drug monitoring may be needed.
See this image and copyright information in PMC

References

    1. Ahmad Z., Peloquin C.A., Singh R.P., Derendorf H., Tyagi S., Ginsberg A., Grosset J.H., Nuermberger E.L. PA-824 exhibits time-dependent activity in a murine model of tuberculosis. Antimicrob. Agents Chemother. 2011 Jan;55(1):239–245. doi: 10.1128/AAC.00849-10. - DOI - PMC - PubMed
    1. Bahuguna A., Rawat D.S. An overview of new antitubercular drugs, drug candidates, and their targets. Med. Res. Rev. 2020 Jan;40(1):263–292. doi: 10.1002/med.21602. - DOI - PubMed
    1. Black T.A., Buchwald U.K. The pipeline of new molecules and regimens against drug-resistant tuberculosis. J Clin Tuberc Other Mycobact Dis. 2021;25 doi: 10.1016/j.jctube.2021.100285. Published 2021 Nov 5. - DOI - PMC - PubMed
    1. Cherian J., Choi I., Nayyar A., Manjunatha U.H., Mukherjee T., Lee Y.S., Boshoff H.I., Singh R., Ha Y.H., Goodwin M., Lakshminarayana S.B., Niyomrattanakit P., Jiricek J., Ravindran S., Dick T., Keller T.H., Dartois V., Barry C.E., 3rd Structure-activity relationships of antitubercular nitroimidazoles. 3. Exploration of the linker and lipophilic tail of ((s)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-yl)-(4-trifluoromethoxybenzyl)amine (6-amino PA-824) J. Med. Chem. 2011 Aug 25;54(16):5639–5659. doi: 10.1021/jm1010644. Epub 2011 Jul 26. - DOI - PMC - PubMed
    1. Conradie F., Diacon A.H., Ngubane N., Howell P., Everitt D., Crook A.M., Mendel C.M., Egizi E., Moreira J., Timm J., McHugh T.D., Wills G.H., Bateson A., Hunt R., Van Niekerk C., Li M., Olugbosi M., Spigelman M., Nix-TB Trial Team Treatment of highly drug-resistant pulmonary tuberculosis. N. Engl. J. Med. 2020 Mar 5;382(10):893–902. doi: 10.1056/NEJMoa1901814. - DOI - PMC - PubMed

LinkOut - more resources