Application of quantitative second-line drug susceptibility testing at a multidrug-resistant tuberculosis hospital in Tanzania.
Application of quantitative second-line drug susceptibility testing at a multidrug-resistant tuberculosis hospital in Tanzania.
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DOI：
10.1186/1471-2334-13-432
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发表时间：
2013-09-14
影响因子：
3.7
通讯作者：
Heysell SK
中科院分区：
文献类型：
--
作者：
Mpagama SG;Houpt ER;Stroup S;Kumburu H;Gratz J;Kibiki GS;Heysell SK
对用于治疗耐多药结核病的二线药物缺乏快速可靠的药敏试验可能会限制治疗的成功。对转诊至坦桑尼亚Kibong 'oto国家结核病医院接受二线结核病治疗的患者的结核分枝杆菌分离株进行了确证性物种形成和敏感性试验。对二线处方集中可用的所有药物在MYCOTB Sensititre平板上进行最小抑菌浓度（MIC）检测。如果MIC处于耐药折点或比耐药折点低一个稀释度，我们选择将分离株归类为临界敏感。M.对结核病DNA中的rpoB（利福平）、inhA（异烟肼、乙硫异烟胺）、katG（异烟肼）、embB（乙胺丁醇）、gyrA（氟喹诺酮类）、rrs（阿米卡星、卡那霉素、卷曲霉素）、eis（卡那霉素）和pncA（吡嗪酰胺）的耐药突变进行测序。在22株来自接受二线结核治疗的患者的分离株中，13株（59%）为耐多药结核，其余为其他耐药模式。MIC检测确定了3株（14%）对乙硫异烟胺耐药的分离株，另有8株（36%）具有临界敏感性。没有分离株对氧氟沙星耐药，但有10株（45%）为临界敏感。阿米卡星在15例（68%）中完全敏感，而卡那霉素仅为11例（50%）。所有13株可用于测序的分离株均不存在gyrA、rrs或eis耐药突变，但6株（46%）存在导致氨基酸改变或终止密码子的pncA突变。10例（77%）耐多药结核病患者至少有一种药物可以根据这些结果进行逻辑修改（中位数2;最大值4）。最常见的修改是从乙硫烟胺变更为对氨基水杨酸，以及使用更高剂量的左氧氟沙星。在坦桑尼亚，定量二线药敏试验可以提供信息并改变耐多药结核病管理，而不受耐药突变的影响。需要进行进一步的业务研究。
Lack of rapid and reliable susceptibility testing for second-line drugs used in the treatment of multidrug-resistant tuberculosis (MDR-TB) may limit treatment success. Mycobacterium tuberculosis isolates from patients referred to Kibong’oto National TB Hospital in Tanzania for second-line TB treatment underwent confirmatory speciation and susceptibility testing. Minimum inhibitory concentration (MIC) testing on MYCOTB Sensititre plates was performed for all drugs available in the second-line formulary. We chose to categorize isolates as borderline susceptible if the MIC was at or one dilution lower than the resistance breakpoint. M. tuberculosis DNA was sequenced for resistance mutations in rpoB (rifampin), inhA (isoniazid, ethionamide), katG (isoniazid), embB (ethambutol), gyrA (fluoroquinolones), rrs (amikacin, kanamycin, capreomycin), eis (kanamycin) and pncA (pyrazinamide). Of 22 isolates from patients referred for second-line TB treatment, 13 (59%) were MDR-TB and the remainder had other resistance patterns. MIC testing identified 3 (14%) isolates resistant to ethionamide and another 8 (36%) with borderline susceptibility. No isolate had ofloxacin resistance, but 10 (45%) were borderline susceptible. Amikacin was fully susceptible in 15 (68%) compared to only 11 (50%) for kanamycin. Resistance mutations were absent in gyrA, rrs or eis for all 13 isolates available for sequencing, but pncA mutation resultant in amino acid change or stop codon was present in 6 (46%). Ten (77%) of MDR-TB patients had at least one medication that could have logically been modified based on these results (median 2; maximum 4). The most common modifications were a change from ethioniamide to para-aminosalicylic acid, and the use of higher dose levofloxacin. In Tanzania, quantitative second-line susceptibility testing could inform and alter MDR-TB management independent of drug-resistance mutations. Further operational studies are warranted.
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影响因子：
--
作者：
Patil M
通讯作者：
Patil M
DOI：
10.1086/653115
发表时间：
2010-07-01
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Jacobson KR;Tierney DB;Jeon CY;Mitnick CD;Murray MB
通讯作者：
Murray MB
影响因子：
4.9
作者：
Morlock, GP;Metchock, B;Cooksey, RC
通讯作者：
Cooksey, RC
影响因子：
15.8
作者：
Resch, Stephen C.;Salomon, Joshua A.;Weinstein, Milton C.
通讯作者：
Weinstein, Milton C.
影响因子：
56.3
作者：
Caminero, Jose A.;Sotgiu, Giovanni;Migliori, Giovanni Battista
通讯作者：
Migliori, Giovanni Battista