Mycobacteriology Research Center, NRITLD, Sheheed, Beheshti University of Medical Science, Tehran, Iran.
Am J Ther. 2011 Sep;18(5):343-9. doi: 10.1097/MJT.0b013e3181dd60ec.
Currently, the Category (CAT) II regimen is recommended for patients who have failed the CAT I regimen. We have determined before that prevalence of multidrug-resistant tuberculosis (MDR TB) is relatively high among these patients. On the other hand, the retreatment success rate with CAT II in CAT I treatment failures and defaults is nearly 50%. Therefore, we tried to find another strategy with a higher success rate. From January 2004 to November 2007, 105 patients with pulmonary TB, who failed a prior CAT I regimen or with more than one course of irregular anti-TB treatment, were included in this study, whereas five cases with nontuberculous mycobacteria were excluded. Drug susceptibility testing (DST), for first line anti-TB drugs, and polymerase chain reaction were performed. By the time of availability of DST that took 3 to 4 months, a pilot protocol consisted of isoniazid, rifampin, ethambutol, ofloxacin, cycloserine, and amikacin was started. Then therapeutic regimen was adjusted based on four categories of DST pattern: sensitive, non-MDR pattern, MDR pattern, and culture-negative. Sensitive patients received the standard CAT I regimen, non-MDR patients an individualized regimen based on DST, MDR patients a standard second-line regimen, and culture-negatives a standard CAT I plus a 6-month injectable agent. Treatment outcomes were categorized and analyzed. Forty-eight patients with prior CAT I treatment failure and 52 with more than one irregular treatment courses were included in the analysis. Six percent of subjects had confirmed HIV infection. Seventy-two percent of subjects were assigned to a good outcome and 28% were assigned to a poor outcome group. Seventeen percent were culture-negative. Regarding DST pattern, 13% isolated strains were completely sensitive to first-line drugs. 53% strains were MDR, 10% monodrug-resistant, and 7% polydrug-resistant. There was no significant association between DST pattern and outcome (P = 0.13). The irregular regimen was associated with MDR TB as twice as CAT I regimen failure (69.2% versus 35.4%, P = 0.004). Patients with MDR TB significantly experienced more side effects than non-MDR-TBs (47% versus 27%, P = 0.102). Of 100 patients, 72% were cured, 5% abandoned treatment, 12% died, 6% were classified as treatment failures, 1% relapsed, and 5% were transferred out. Of 53 patients with MDR TB, 33 subjects were cured and seven died. All together, successful outcome was achieved in 62.2%, 76%, and 76% of MDR TB, non-MDR TB, and completely sensitive cases, respectively. A retreatment strategy based on DST and replacing the Category II regimen with an intermediate regimen called revised CAT II may improve clinical outcomes among Category I treatment failures and defaults who found to have active, infectious MDR TB. This strategy significantly reduces delays to MDR TB diagnosis and to the initiation of MDR TB therapy. Success rate of this strategy is 62.2% and 72% in MDR TB and overall CAT I failure cases and defaulters, respectively.
目前，对于 CAT I 方案失败的患者推荐使用 CAT II 方案。我们之前已经确定，这些患者中耐多药结核病（MDR TB）的患病率相对较高。另一方面，CAT II 方案在 CAT I 治疗失败和中断的患者中的治疗成功率接近 50%。因此，我们试图寻找一种成功率更高的策略。从 2004 年 1 月至 2007 年 11 月，共有 105 例既往 CAT I 方案失败或有多次不规则抗结核治疗史的肺结核患者纳入本研究，其中 5 例为非结核分枝杆菌患者被排除在外。进行了一线抗结核药物的药物敏感性试验（DST）和聚合酶链反应。在 DST 可用的 3 至 4 个月时间内，开始使用异烟肼、利福平、乙胺丁醇、氧氟沙星、环丝氨酸和阿米卡星的试点方案。然后根据 DST 四种模式调整治疗方案：敏感、非 MDR 模式、MDR 模式和培养阴性。敏感患者接受标准的 CAT I 方案治疗，非 MDR 患者根据 DST 制定个体化方案，MDR 患者接受标准二线方案治疗，培养阴性患者接受标准 CAT I 加 6 个月注射剂。对治疗结果进行分类和分析。在 48 例 CAT I 治疗失败的患者和 52 例多次不规则治疗的患者中进行了分析。6%的患者有确诊的 HIV 感染。72%的患者预后良好，28%的患者预后较差。17%的患者培养阴性。关于 DST 模式，13%分离株对一线药物完全敏感。53%的菌株为 MDR，10%为单耐药，7%为多耐药。DST 模式与结果之间无显著相关性（P=0.13）。不规则方案与 CAT I 方案失败的 MDR TB 发生率是 CAT I 方案的两倍（69.2%比 35.4%，P=0.004）。MDR TB 患者明显比非 MDR-TB 患者经历更多的副作用（47%比 27%，P=0.102）。在 100 例患者中，72%治愈，5%放弃治疗，12%死亡，6%被归类为治疗失败，1%复发，5%转出。在 53 例 MDR TB 患者中，33 例治愈，7 例死亡。总的来说，MDR TB、非 MDR TB 和完全敏感病例的治疗成功率分别为 62.2%、76%和 76%。基于 DST 的复治策略和用中间方案（称为修订后的 CAT II 方案）替代 CAT II 方案，可能会提高 CAT I 方案失败和中断患者中活跃、传染性 MDR TB 的临床疗效。该策略显著减少了 MDR TB 诊断和 MDR TB 治疗开始的延误。该策略的成功率分别为 MDR TB 和 CAT I 方案失败和中断的所有病例的 62.2%和 72%。
