Mycobactericidal activity of sutezolid (PNU-100480) in sputum (EBA) and blood (WBA) of patients with pulmonary tuberculosis.
Mycobactericidal activity of sutezolid (PNU-100480) in sputum (EBA) and blood (WBA) of patients with pulmonary tuberculosis.
复制标题
DOI：
10.1371/journal.pone.0094462
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Diacon AH
中科院分区：
文献类型：
--
作者：
Wallis RS;Dawson R;Friedrich SO;Venter A;Paige D;Zhu T;Silvia A;Gobey J;Ellery C;Zhang Y;Eisenach K;Miller P;Diacon AH
舒特唑胺（PNU-100480）是一种利奈唑胺类似物，在中空纤维、全血和小鼠模型中对结核分枝杆菌具有上级杀菌活性。与利奈唑胺一样，它不受对标准结核病药物产生耐药性的突变的影响。本研究的舒特唑胺是其在结核病患者的第一次。痰涂片阳性结核病患者在治疗的前14天随机分配至舒替唑胺600 mg BID（N = 25）或1200 mg QD（N=25）或标准4种药物治疗（N= 9）。 通过琼脂上的菌落计数和自动液体培养中的阳性时间监测对痰液中分枝杆菌负荷（早期杀菌活性或EBA）的影响。还在接种M的离体全血培养物（全血杀菌活性或WBA）中测量杀菌活性。结核病H37 Rv.所有患者均完成指定治疗，并根据方案开始后续标准TB治疗。对于所有治疗和两种监测方法，14天间隔内痰液中杀菌活性的90%置信区间（CI）不包括0，累积WBA也是如此。未发生治疗相关严重不良事件、提前停药或因实验室检查异常而降低剂量。对QT间期没有影响。7例接受舒特唑胺治疗的患者（14%）在第14天出现一过性、无症状的ALT升高至173±34 U/L，随后迅速恢复正常;均不符合Hy的严重肝损伤标准。在痰液和血液中很容易检测到舒替唑胺600 mg BID或1200 mg QD的分枝杆菌杀菌活性。这两种方案一般都是安全的，耐受性良好。舒特唑胺在结核病治疗中的进一步研究是必要的。ClinicalTrials.gov NCT01225640
Sutezolid (PNU-100480) is a linezolid analog with superior bactericidal activity against Mycobacterium tuberculosis in the hollow fiber, whole blood and mouse models. Like linezolid, it is unaffected by mutations conferring resistance to standard TB drugs. This study of sutezolid is its first in tuberculosis patients. Sputum smear positive tuberculosis patients were randomly assigned to sutezolid 600 mg BID (N = 25) or 1200 mg QD (N = 25), or standard 4-drug therapy (N = 9) for the first 14 days of treatment. Effects on mycobacterial burden in sputum (early bactericidal activity or EBA) were monitored as colony counts on agar and time to positivity in automated liquid culture. Bactericidal activity was also measured in ex vivo whole blood cultures (whole blood bactericidal activity or WBA) inoculated with M. tuberculosis H37Rv. All patients completed assigned treatments and began subsequent standard TB treatment according to protocol. The 90% confidence intervals (CI) for bactericidal activity in sputum over the 14 day interval excluded zero for all treatments and both monitoring methods, as did those for cumulative WBA. There were no treatment-related serious adverse events, premature discontinuations, or dose reductions due to laboratory abnormalities. There was no effect on the QT interval. Seven sutezolid-treated patients (14%) had transient, asymptomatic ALT elevations to 173±34 U/L on day 14 that subsequently normalized promptly; none met Hy's criteria for serious liver injury. The mycobactericidal activity of sutezolid 600 mg BID or 1200 mg QD was readily detected in sputum and blood. Both schedules were generally safe and well tolerated. Further studies of sutezolid in tuberculosis treatment are warranted. ClinicalTrials.gov NCT01225640
登录
查看更多内容
DOI：
10.1164/rccm.200806-892oc
发表时间：
2008-12-01
影响因子：
24.7
作者：
Dietze, Reynaldo;Hadad, David Jamil;Johnson, John L.
通讯作者：
Johnson, John L.
影响因子：
3.8
作者：
Venketaraman, Vishwanath;Millman, Ariel;Connell, Nancy D.
通讯作者：
Connell, Nancy D.
DOI：
10.1164/rccm.201105-0850oc
发表时间：
2012-03-15
影响因子：
24.7
作者：
Singanayagam, Aran;Sridhar, Saranya;Kon, Onn Min
通讯作者：
Kon, Onn Min
影响因子：
4.9
作者：
McKee, EE;Ferguson, M;Marks, TA
通讯作者：
Marks, TA
影响因子：
4.9
作者：
Diacon, Andreas H.;Dawson, Rodney;Spigelman, Melvin K.
通讯作者：
Spigelman, Melvin K.