Study on the effects of D-Cycloserine combined with Rifampicin and Isoniazid on drug-resistant Mycobacterium tuberculosis in vitro
CHEN Shengjie1 LI Xi1 LI Chao2▲
1.Department of Clinical Laboratory, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Province, Guangzhou 510405, China;
2.Department of Central Laboratory, Foshan Women and Children Hospital Affiliated to Southern Medical University, Guangdong Province, Foshan 528000, China
Abstract Objective To evaluate the effect of D-Cycloserine (DCS) combined with Rifampicin and Isoniazid on drug-resistant Mycobacterium tuberculosis in vitro. Methods The minimum inhibitory concentration (MIC) of 38 clinical isolates against DCS, Rifampicin and Isoniazid were determined by microporous plate Alamar Blue method, the combined effect of DSC and Rifampicin and Isoniazid in vitro was detected by checkerboard dilution method, and the combined effect was determined by fractional inhibitory concentration index (FICI). Results Seven strains (18.4%) displayed synergistic effect in DCS combination with Rifampicin, and combined MIC of 24 strains (63.2%) reduced several concentration gradients. After combined DSC with Isoniazid, 5 strains (13.2%) showed synergistic effect, and the combined MIC of 22 strains (57.9%) reduced several concentration gradients. No antagonistic effect was observed with either combination drug regimen. MIC50 and MIC90 decreased after DSC combined with Rifampicin and Isoniazid. Conclusion DSC combined with Rifampicin and Isoniazid can reduce the resistance of clinical drug-resistant strains to varying degrees. DCS combined with therapy is beneficial to the treatment of drug-resistant tuberculosis patients.
CHEN Shengjie1 LI Xi1 LI Chao2▲. Study on the effects of D-Cycloserine combined with Rifampicin and Isoniazid on drug-resistant Mycobacterium tuberculosis in vitro[J]. 中国医药导报, 2022, 19(16): 26-29,37.
[1] World Health Organization. Global tuberculosis report 2020 [R]. Geneva：World Health Organization，2020.
[2] 王飞，陈彬，周琳，等.耐多药肺结核患者抗结核药物所致不良反应发生情况[J].中华传染病杂志，2017，35（2）：83-87.
[3] Dheda K，Gumbo T，Martens G，et al. The epidemiology，pathogenesis，transmission，diagnosis and management of multidrug-resistant，extensively drug-resistant，and incurable tuberculosis [J]. Lancet Respir Med，2017，5：291-360.
[4] Dookie N，Rabaran S，Padayatci N，et al. Evolution of drug resistance in Mycobacterium tuberculosis：a review on the molecular determinants of resistance and implications for personalized care [J]. J Antimicrob Chemother，2018，73（5）：1138-1151.
[5] Bhusal Y，Shiohira CM，Yamane N，et al. Determination of in vitro synergy when three antimicrobialagents are combined against Mycobacterium tuberculosis [J]. Int J Antimicrob Agents，2005，26（4）：292-297.
[6] Caminero JA，Sotgiu G，Zumla A，et al. Best drug treatment for multidrug-resistant and extensively drug-resistant tuberculosis [J]. Lancet Infect Dis，2010，10：621-629.
[7] Chiara CD，Hom?觢ak M，Prosser GA，et al. D-Cycloserine destruction by alanine racemase and the limit of irreversible inhibition [J]. Nat Chem Biol，2020，16（6）：686-694.
[8] Franco TMA，Favrot L，Vergnole O，et al. Mechanism-Based Inhibition of the Mycobacterium tuberculosis Branched-Chain Aminotransferase by d-and l-Cycloserine [J]. ACS Chem Biol，2017，12（5）：1235-1244.
[9] Falzon D，Jaramillo E，Schünemann HJ，et al. WHO guidelines for the programmatic management of drug-resistant tuberculosis：2011 update [J]. Eur Respir J，2011，38（3）：516-528.
[10] Masjedi MR，Tabarsi P，Chitsaz E，et al. Outcome of treatment of MDR-TB patients with standardised regimens，Iran，2002—2006 [J]. Int J Tuberc Lung Dis，2008，12（7）：750-755.
[11] Walt ML，Shean K，Becker P，et al. Treatment Outcomes and Adverse Drug Effects of Ethambutol，Cycloserine，and Terizidone for the Treatment of Multidrug-Resistant Tuberculosis in South Africa [J]. Antimicrob Agents Chemother，2020，65（1）：e00744-20.
[12] Moody J. Synergism testing： broth microdilution checkerboard and broth macrodilution method [M]. Clinical microbiology procedures handbook，2004：1-28.
[13] Santos NCS，Scodro RBL，Leal DC，et al. Determination of minimum bactericidal concentration，in single or combination drugs，against Mycobacterium tuberculosis [J]. Future Microbiol，2020，15：107-114.
[14] Cho S，Lee HS，Franzblau S. Microplate Alamar Blue Assay （MABA） and Low Oxygen Recovery Assay （LORA） for Mycobacterium tuberculosis [J]. Methods Mol Biol，2015，1285：281-292.
[15] Koh WJ，Hong G，Kim SY，et al. Treatment of refractory Mycobacterium avium complex lung disease with a moxifloxacin-containing regimen [J]. Antimicrob Agents Che-mother，2013，57（5）：2281-2285.
[16] Guo N，Wu J，Fan J，et al. In vitro activity of isoimperatorin，alone and in combination，against Mycobacterium tuberculosis [J]. Lett Appl Microbiol，2014，58（4）：344-349.
[17] Maltempe FG，Ferraioli KRC，Amaral RCR，et al. Activity of rifampicin and linezolid combination in Mycobacterium tuberculosis [J]. Tuberculosis （Edinb），2017，104：24-29.
[18] Dousa KM，Kurz SG，Bark CM，et al. Drug-Resistant Tuberculosis：A Glance at Progress and Global Challenges [J]. Infect Dis Clin North Am，2020，34（4）：863-886.
[19] Desjardins CA，Cohen KA，Munsamy V，et al. Genomic and functional analyses of Mycobacterium tuberculosis strains implicate ald in D-cycloserine resistance [J]. Nat Genet，2016，48（5）：544-551.
[20] Nakatani Y，Opel-Reading HK，Merker M，et al. Role of Alanine Racemase Mutations in Mycobacterium tuberculosisd-Cycloserine Resistance [J]. Antimicrob Agents Chemother，2017，61（12）：e01575-17.
[21] Cho S，Lee HS，Franblau S，et al. Microplate Alamar Blue Assay （MABA） and Low Oxygen Recovery Assay （LORA） for Mycobacterium tuberculosis [J]. Methods Mol Biol，2015，1285：281-292.
[22] Shao J，Xiong L，Zhang MX，et al. Report： Synergism of sodium bicarbonate and baicalin against clinical Candida albicans isolates via broth microdilution method and checkerboard assay [J]. Pak J Pharm Sci，2019，32（3）：1103-1105.
[23] Suzuki T，Ohashi Y. Combination effect of antibiotics against bacteria isolated from keratitis using fractional inhibitory concentration index [J]. Cornea，2013，32（7）：e156-60.
[24] Hegeto LA，Ferraci KRC，Vasconcelos SSN，et al. In vitro combinatory activity of piperine and anti-tuberculosis drugs in Mycobacterium tuberculosis [J]. Tuberculosis （Edinb），2018，111：35-40.
[25] Keiser TL，Purdy GE. Killing Mycobacterium tuberculosis In Vitro：What Model Systems Can Teach Us.Microbiol [J]. Spectr，2017，5（3）：10.1128
