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High-Dose Isoniazid Speeds Recovery From Multidrug-Resistant TB
By C. Vidyashankar. MD
NEW YORK (Reuters Health) Feb 29 - High-dose isoniazid (INH) as an adjuvant to second-line agents for multidrug-resistant TB reduces the time to sputum negativity and improves short-term outcomes, researchers from India report.
Dr. S. K. Katiyar from the Ganesh Shankar Vidyarthi Memorial Medical College in Kanpur, Dr. M. Mamtani from the Lata Medical Research Foundation in Nagpur, and their teams evaluated the role of high-dose INH as an adjuvant to kanamycin, levofloxacin, prothionamide, cycloserine and sodium para-aminosalicylic acid in HIV-negative adults with previously diagnosed pulmonary TB.
In the randomized trial, 42 patients received high-dose INH (16-18 mg/kg/day), 40 received standard-dose INH (5mg/kg/day), and 41 received placebo. All were assessed bimonthly with biochemical studies, sputum smear and cultures. Chest x-rays were taken at baseline and at 1 year after the start of treatment.
Results are published in the February issue of the International Journal of Tuberculosis and Lung Disease.
The median times until a negative sputum culture were 3.4, 6.4 and 6.6 months in the high-dose, standard-dose, and placebo groups, respectively. Radiological clearance of lesions as measured by standard scores was also maximal in the high-dose INH group, according to the article.
At 6 months after the start of treatment, sputum cultures were negative in 73.8% of patients in the high-dose group, versus 45% in the standard-dose group and 48.8% in the placebo patients, the researchers report. By one year, sputum clearance rates were similar between the groups.
Use of adjuvant high-dose INH could prevent nearly two-thirds of treatment failures after six months of treatment, the researchers estimate.
\"Multidrug-resistant TB patients tend to harbor tuberculosis bacteria that are notoriously mixed in terms of their susceptibility to first line of treatment using a standard dose of INH,\" Dr. Hemant Kulkarni, the corresponding author from San Antonio, Texas, told Reuters Health by email. High-dose INH may have a role in clearing sensitive and low-resistance strains, he adds.
Although peripheral neuropathy was more frequent in the high-dose INH group, hepatic derangement was similar in both the high- and standard-dose INH groups, Dr. Kulkarni said. \"The incidence of peripheral neuropathy can be substantially reduced by pyridoxine supplementation,\" he recommends.
When asked whether high-dose INH should be universally used with second-line agents for multidrug-resistant TB, Dr. Kulkarni responded, \"Theoretically, yes. Still, where there are resources and finances available for an 'individualized treatment,' one would prefer a different approach. For more resource-limited scenarios, however, our results suggest that it will be beneficial to use high-dose INH...because INH is quite inexpensive.\"
Int J Tuberc Lung Dis 2008;12:139-145.
大剂量异烟肼可逆转结核多重耐药纽约（路透社健康）2月29----来自印度的研究者们报道： 大剂量异烟肼（INH）作为多重耐药结核菌的二线辅助用药，可减少痰转阴时间，提高短期疗法疗效。Dr. S. K. Katiya（Ganesh Shankar Vidyarthi Memoria医学院，坎普尔）、Dr. M. Mamtani（Lata医学研究基金会，Nagpur）和他们的团队评价大剂量INH作为卡那霉素、左氧氟沙星、丙硫异烟胺、恶唑霉素和对氨基水杨酸钠辅助用药在HIV阴性的肺结核患者中的作用。在这项随机治疗中，42名患者接受大剂量INH（16-18 mg/kg/day）治疗，40接受标准剂量INH(5mg/kg/day),41名接受安慰剂。所有患者均接受两月一次的生化检查、痰涂和痰培养。开始治疗前和治疗一年后接受胸部x线片检查。结果发表在二月份International Journal of Tuberculosis and Lung Disease杂志上。大剂量、标准剂量和安慰剂组的中位痰培养转阴时间分别为3.4、6.4和6.6月。用标准分数评价的放射学病灶清除率亦是大剂量INH最高，根据文章报道。研究者报道：治疗6个月后，大剂量组73.8%患者痰培养阴性，标准剂量组为45%，安慰剂组为48.8%。一年后，各组间痰清除率类似。研究者评价道：使用辅助的大剂量INH可以防止治疗6个月后约三分之二的治疗失败
“\"Multidrug-resistant TB patients tend to harbor tuberculosis bacteria that are notoriously mixed in terms of their susceptibility to first line of treatment using a standard dose of INH” Dr. Hemant Kulkarni（通讯作者，来自San Antonio, 得克萨斯）在email中说道。大剂量INH可能在敏感性和低抵抗性方面有重要作用，他补充道。尽管外周神经病变在大剂量INH组较高，肝脏损害在大剂量和标准剂量组之间类似，Dr. Kulkarni说。“外周神经病变可补充维生素B6来减低，”他介绍道。当问及是否大剂量INH作为二线药物辅助药物普遍应用与多重耐药性结核菌时，Dr. Kulkarni说“理论上是这样的。然而，有资源和财政支持用于‘个体化治疗’，人们更倾向与不同的治疗方案。更多资源有限的情况下，然而，我们的研究结果表明使用高剂量异烟肼有利，因为异烟肼是相当便宜的。” |
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发表于 2008-3-14 16:27:07
