Activity of Contezolid Against Methicillin-Resistant , Vancomycin-Resistant , and Strains With Linezolid Resistance Genes From China

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2021 Sep 7

PMID 34489919

Citations 10

Authors

Siheng Wang

Chang Cai

Yingbo Shen

Chengtao Sun

Qingxin Shi

Ningjun Wu

Shufang Zheng

Jiao Qian

Rong Zhang

Hongwei Zhou

Affiliations

Soon will be listed here.

Abstract

Contezolid is a novel oxazolidinone, which exhibits potent activity against gram-positive bacteria, including methicillin-resistant (MRSA), vancomycin-resistant (VRE), and penicillin-resistant (PRSP). In this study, the activity of contezolid was compared with linezolid (LZD), tigecycline (TGC), teicoplanin (TEC), vancomycin (VA), daptomycin (DAP), and florfenicol (FFC) against MRSA and VRE strains isolated from China. Contezolid revealed considerable activity against MRSA and VRE isolates with MIC values of 0.5 and 1.0 μg/mL, respectively. For VRE strains with different resistance genotypes, including vanA- and vanM-type strains, contezolid did not exhibit significantly differential antibacterial activity. Furthermore, the antimicrobial activity of contezolid is similar to or slightly better than that of linezolid against MRSA and VRE strains. Subsequently, the activity of contezolid was tested against strains carrying linezolid resistance genes, including carrying gene and carrying gene. The results showed that contezolid exhibited similar antimicrobial efficacy to linezolid against strains with linezolid resistance genes. In general, contezolid may have potential benefits to treat the infections caused by MRSA and VRE pathogens.

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References

Bassetti M, Del Puente F, Magnasco L, Giacobbe D . Innovative therapies for acute bacterial skin and skin-structure infections (ABSSSI) caused by methicillin-resistant : advances in phase I and II trials. Expert Opin Investig Drugs. 2020; 29(5):495-506. DOI: 10.1080/13543784.2020.1750595. View

Hoskins A, Worth L, Imam N, Johnson S, Bull A, Richards M . Validation of healthcare-associated infection surveillance in smaller Australian hospitals. J Hosp Infect. 2017; 99(1):85-88. DOI: 10.1016/j.jhin.2017.10.006. View

Osei Sekyere J, Mensah E . Molecular epidemiology and mechanisms of antibiotic resistance in Enterococcus spp., Staphylococcus spp., and Streptococcus spp. in Africa: a systematic review from a One Health perspective. Ann N Y Acad Sci. 2019; 1465(1):29-58. DOI: 10.1111/nyas.14254. View

Zahedi Bialvaei A, Rahbar M, Yousefi M, Asgharzadeh M, Kafil H . Linezolid: a promising option in the treatment of Gram-positives. J Antimicrob Chemother. 2016; 72(2):354-364. DOI: 10.1093/jac/dkw450. View

Zurenko G, Gibson J, Shinabarger D, Aristoff P, Ford C, Tarpley W . Oxazolidinones: a new class of antibacterials. Curr Opin Pharmacol. 2002; 1(5):470-6. DOI: 10.1016/s1471-4892(01)00082-0. View

Evers S, Courvalin P . Detection of glycopeptide resistance genotypes and identification to the species level of clinically relevant enterococci by PCR. J Clin Microbiol. 1995; 33(1):24-7. PMC: 227872. DOI: 10.1128/jcm.33.1.24-27.1995. View

Lee E, Caffrey A . Thrombocytopenia with Tedizolid and Linezolid. Antimicrob Agents Chemother. 2017; 62(1). PMC: 5740346. DOI: 10.1128/AAC.01453-17. View

Eckburg P, Ge Y, Hafkin B . Single- and Multiple-Dose Study To Determine the Safety, Tolerability, Pharmacokinetics, and Food Effect of Oral MRX-I versus Linezolid in Healthy Adult Subjects. Antimicrob Agents Chemother. 2017; 61(4). PMC: 5365677. DOI: 10.1128/AAC.02181-16. View

Sadowy E . Linezolid resistance genes and genetic elements enhancing their dissemination in enterococci and streptococci. Plasmid. 2018; 99:89-98. DOI: 10.1016/j.plasmid.2018.09.011. View

10.

Ruiz-Ripa L, Fessler A, Hanke D, Eichhorn I, Azcona-Gutierrez J, Perez-Moreno M . Mechanisms of Linezolid Resistance Among Enterococci of Clinical Origin in Spain-Detection of - and (D)-Carrying . Microorganisms. 2020; 8(8). PMC: 7464793. DOI: 10.3390/microorganisms8081155. View

11.

Hashemian S, Farhadi T, Ganjparvar M . Linezolid: a review of its properties, function, and use in critical care. Drug Des Devel Ther. 2018; 12:1759-1767. PMC: 6014438. DOI: 10.2147/DDDT.S164515. View

12.

Li C, Zhai Q, Wang X, Hu X, Li G, Zhang W . In vivo antibacterial activity of MRX-I, a new oxazolidinone. Antimicrob Agents Chemother. 2014; 58(4):2418-21. PMC: 4023790. DOI: 10.1128/AAC.01526-13. View

13.

Wang W, Voss K, Liu J, Gordeev M . Nonclinical Evaluation of Antibacterial Oxazolidinones Contezolid and Contezolid Acefosamil with Low Serotonergic Neurotoxicity. Chem Res Toxicol. 2021; 34(5):1348-1354. DOI: 10.1021/acs.chemrestox.0c00524. View

14.

Meng J, Zhong D, Li L, Yuan Z, Yuan H, Xie C . Metabolism of MRX-I, a novel antibacterial oxazolidinone, in humans: the oxidative ring opening of 2,3-Dihydropyridin-4-one catalyzed by non-P450 enzymes. Drug Metab Dispos. 2015; 43(5):646-59. DOI: 10.1124/dmd.114.061747. View

15.

Stevenson K, Searle K, Stoddard G, Samore M . Methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci in rural communities, western United States. Emerg Infect Dis. 2005; 11(6):895-903. PMC: 3367578. DOI: 10.3201/eid1106.050156. View

16.

Asokan G, Ramadhan T, Ahmed E, Sanad H . WHO Global Priority Pathogens List: A Bibliometric Analysis of Medline-PubMed for Knowledge Mobilization to Infection Prevention and Control Practices in Bahrain. Oman Med J. 2019; 34(3):184-193. PMC: 6505350. DOI: 10.5001/omj.2019.37. View

17.

Li J, Jiang N, Ke Y, Fessler A, Wang Y, Schwarz S . Characterization of pig-associated methicillin-resistant Staphylococcus aureus. Vet Microbiol. 2017; 201:183-187. DOI: 10.1016/j.vetmic.2017.01.017. View

18.

Shinabarger D . Mechanism of action of the oxazolidinone antibacterial agents. Expert Opin Investig Drugs. 2005; 8(8):1195-202. DOI: 10.1517/13543784.8.8.1195. View

19.

Carvalhaes C, Duncan L, Wang W, Sader H . Activity and Potency of the Novel Oxazolidinone Contezolid (MRX-I) Tested against Gram-Positive Clinical Isolates from the United States and Europe. Antimicrob Agents Chemother. 2020; 64(11). PMC: 7577137. DOI: 10.1128/AAC.01195-20. View

20.

Huang Y, Xu Y, Liu S, Wang H, Xu X, Guo Q . Selection and characterisation of Staphylococcus aureus mutants with reduced susceptibility to the investigational oxazolidinone MRX-I. Int J Antimicrob Agents. 2014; 43(5):418-22. DOI: 10.1016/j.ijantimicag.2014.02.008. View