Prospects of contezolid (MRX-I) against multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis

Abstract

Tuberculosis has become a great global public health threat. Compared with drug-susceptible tuberculosis (TB), the treatment regimens for multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) involve more severe adverse events and poorer treatment outcomes. Linezolid (LZD) is the first oxazolidinones used for TB. Thanks to its potent activity against Mycobacterium tuberculosis, LZD has become one of the key agents in the regimens against MDR/XDR-TB. However, this drug may cause intolerability and other adverse events. Contezolid, another novel oxazolidinone, can also inhibit M. tuberculosis, still with fewer adverse effects compared with LZD. This paper is to prospect the potentials of contezolid in the treatment of MDR/XDR-TB, with focus on its efficacy and possible adverse effects.

Case report: Successful treatment with contezolid in a patient with tuberculous meningitis who was intolerant to linezolid

“…Contezolid is a novel oxazolidinone drug designed to address the myelosuppression and MAO inhibition associated with linezolid. It can inhibit the formation of a functional 70S initiation complex required for bacterial replication and has a broad antibacterial spectrum against Staphylococcus, Streptococcus, Enterococcus, Mycobacterium tuberculosis, nontuberculous mycobacteria, and Nocardia (6,(9)(10)(11)(12). A number of studies (13)(14)(15) have confirmed the safety and tolerability of contezolid in healthy Chinese subjects, and a phase III clinical trial (16) in China showed that the incidence of hematological adverse events induced by contezolid during 7-14 days of treatment was significantly lower than that induced by linezolid.…”

In vitro activities of contezolid (MRX-I) against drug-sensitive and drug-resistant Mycobacterium tuberculosis

“…MRX-I had a strong anti-Gram-positive bacterial ability with a similar efficacy to that of LZD, and the clinical cure rates of MRX-I and LZD were reported to be 93.0% and 93.4% at post-treatment visits, respectively, in a critical phase III study (CTR20150855) for the treatment of complex skin and soft-tissue infections in China which was conducted in 50 clinical centers ( 10 , 11 ). Besides, compared with LZD, MRX-I has more safety advantages, including tolerance and minimal adverse effects (such as hematological adverse events and myelosuppression) ( 12 ). Additionally, it has been reported that MRX-I exhibits anti- M .…”

Tuberculosis patients with special clinical conditions treated with contezolid: three case reports and a literature review

“…In contezolid, the A and B rings have a non-coplanar structure, which enhances the bacterial target binding, thus reducing the risk of drug resistance and killing bacteria more efficiently (4). It reduces the penetration of somatic cells and mitochondria, thus preserving the normal function of mitochondria and effectively reducing the side effects of myelosuppression (5). At present, it has completed phase III clinical trials in China and has been approved for marketing in China in 2021 (6).…”