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氟喹诺酮类药物对来自印度北部阿格拉和坎普尔地区结核分枝杆菌分离株的体外作用。

In vitro effect of fluoroquinolones against Mycobacterium tuberculosis isolates from Agra & Kanpur region of north India.

作者信息

Singh Mradula, Chauhan D S, Gupta Pushpa, Das R, Srivastava R K, Upadhyay Prashant, Singh Pushpendra, Srivastava K, Faujdar Jaya, Jaudaun G P S, Yadav V S, Sharma V D, Venkatesan K, Sachan S, Sachan P, Katoch K, Katoch V M

机构信息

Department of Microbiology & Molecular Biology, National JALMA Institute for Leprosy & Other Mycobacterial Diseases (ICMR), Agra, India.

出版信息

Indian J Med Res. 2009 May;129(5):542-7.

Abstract

BACKGROUND & OBJECTIVE: Fluoroquinolones (FQs) are important drugs used for treatment of drug resistant tuberculosis and are also now being considered as first line drugs to shorten the duration of treatment of tuberculosis (TB). In order to find out useful FQs for treatment of tuberculosis, the comparative efficacy of five FQs, namely, ofloxacin (OFL), ciprofloxacin (CIP), sparfloxacin (SPX), gatifloxacin (GAT) and levofloxacin (LEVX) was studied against Mycobacterium tuberculosis (MTB) isolates obtained from both treated and untreated patients from Agra and Kanpur regions of north India.

METHODS

A total of 162 MTB isolates [including 110 MTB isolates obtained from untreated patients (Cat-I) and 52 isolates from treated patients (Cat-II)] were tested for their susceptibilities to FQs using standard minimum inhibitory concentration (MIC) method on Löwenstein-Jensen medium.

RESULTS

Keeping in view the therapeutically achievable drug levels, it was found that in Cat-I 97.2 per cent (107/110) isolates were sensitive to GAT, 89 per cent (98/110) to LEVX at 1 microg/ml whereas 92.7 per cent (102/110) isolates were inhibited by OFL at 2 microg/ml and 73.6 per cent (81/110) to SPX at 0.5 microg/ml. Only 63.6 per cent (70/110) isolates were found to be sensitive to CIP at 2 microg/ml which increased to 89 per cent (98/110) at 4 microg/ml (higher than achievable peak serum level). On the other hand, among 52 isolates for Cat-II, 37 (71.2%) were found to be sensitive to GAT and 33 (63.5%) to LEVX at 1 microg/ml concentration, 28 (53.8%) to SPX at 0.5 microg/ml whereas 33 (63.5%) and 24 (46.2%) isolates were found to be sensitive to OFL and CIP at 2 microg/ml, respectively.

INTERPRETATION & CONCLUSION: It appears that GAT has higher activity against MTB isolates followed by OFL, LEVX and SPX whereas CIP showed the lowest activity. GAT was also found to be the most effective FQ against multi-drug resistant (MDR) isolates both from Cat-I and Cat-II patients. Thus, except CIP, other FQs showed potential to be included in the treatment regimens of tuberculosis including MDR-TB.

摘要

背景与目的

氟喹诺酮类药物(FQs)是用于治疗耐药结核病的重要药物,目前也被视为缩短结核病(TB)治疗疗程的一线药物。为了找出治疗结核病的有效氟喹诺酮类药物,研究了氧氟沙星(OFL)、环丙沙星(CIP)、司帕沙星(SPX)、加替沙星(GAT)和左氧氟沙星(LEVX)这五种氟喹诺酮类药物对从印度北部阿格拉和坎普尔地区未治疗和已治疗患者中分离出的结核分枝杆菌(MTB)的比较疗效。

方法

采用标准最低抑菌浓度(MIC)法,在罗 - 琴培养基上对总共162株MTB分离株[包括从未治疗患者中获得的110株MTB分离株(类别I)和从已治疗患者中获得的52株分离株(类别II)]进行氟喹诺酮类药物敏感性测试。

结果

考虑到治疗上可达到的药物水平,发现在类别I中,97.2%(107/110)的分离株对加替沙星敏感,89%(98/110)的分离株在1微克/毫升时对左氧氟沙星敏感,而92.7%(102/110)的分离株在2微克/毫升时被氧氟沙星抑制,73.6%(81/110)的分离株在0.5微克/毫升时对司帕沙星敏感。仅63.6%(70/110)的分离株在2微克/毫升时对环丙沙星敏感,在4微克/毫升(高于可达到的血清峰值水平)时增至89%(98/110)。另一方面,在类别II的52株分离株中,37株(71.2%)在1微克/毫升浓度下对加替沙星敏感,33株(63.5%)对左氧氟沙星敏感,28株(53.8%)在0.5微克/毫升时对司帕沙星敏感,而33株(63.5%)和24株(46.2%)分离株在2微克/毫升时分别对氧氟沙星和环丙沙星敏感。

解读与结论

似乎加替沙星对MTB分离株的活性更高,其次是氧氟沙星、左氧氟沙星和司帕沙星;而环丙沙星的活性最低。加替沙星还被发现是对类别I和类别II患者的多药耐药(MDR)分离株最有效的氟喹诺酮类药物。因此,除环丙沙星外,其他氟喹诺酮类药物显示出有可能纳入包括耐多药结核病在内的结核病治疗方案。

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