Objective: To analyze and evaluate the effectiveness of individualized treatment regimen in the therapy of smear-positive retreatment pulmonary tuberculosis with mono-and poly-drug resistance, and therefor to provide information on how to develop rational individualized regimen for retreatment tuberculosis cases with drug resistance. Methods: This was a multi-centered, prospective cohort study. Totally 254 cases of sputum positive tuberculosis with previous treatment history during the period from July 1, 2009 to August 30, 2016 were included in the analysis. All the cases were randomly divided into 3 groups and received therapy after randomization into treatment groups. After 3 months, cases with multidrug resistant tuberculosis, extensively drug-resistant tuberculosis, non-tuberculosis mycobacterial infection and those with smear-positive but culture-negative tuberculosis were excluded according to result of sputum culture and drug susceptibility test (DST). In treatment group A (individualized treatment group), 86 cases with an average age of (42.1±13.7) years for men and (38.5±12.8) years for women, were treated with individualized regimen, which allowed drug replacement on the basis of standard regimen (2SHRZE/6HRE) according to DST result. Treatment duration was recalculated after drug replacement and the total length should be 12 months or more. If the DST result did not show drug resistance, the patients would continue the 8 months' standard treatment. In treatment group B (intensified retreatment regimen group), 86 cases with an average age of (43.2±14.2) years for man and (37.9±14.1) years for women, received intensified retreatment regimen (2HL(2)EZS/2HL(2)EZS(3)/4HL(2)E). The dose for H was 0.3 g/d for patients with body weight <50 kg, and 0.4~0.5 g/d for higher body weight (≥50 kg); The doses for L(2,)E and Z were 0.6 g, 2/w; 0.75, 1/d and 0.5g, 3/d. In treatment group C (standard treatment group), 82 cases with an average of (42.5±11.9) years for man and (38.6±12.8) years for women, were treated with standardized regimen recommended by national tuberculosis program (2HREZS/6HRE). In both group B and C, the total treatment duration was 8 months and the drugs were not replaced for mono-and poly-drug resistance. Treatment outcomes of the 3 groups were analyzed, the status of drug replacement in group A was analyzed, and the adjustment of dose of H and R according to patients' body weight was observed. SPSS 19.0 was used for data analysis. Results: The treatment cure rates for group A, B and C were 73.3%(63/86), 76.7%(66/86) and 50%(41/82), and the treatment success rates were 80.2%(69/86), 84.9%(73/86) and 62.2%(51/82) respectively. Treatment failure was 8.1%(7/86), 4.7%(4/86) and 19.5%(16/82) in 3 groups. There were significant differences in the above indicators for group A and B in comparison with group C(χ(2)=13.127, P=0.001). However, there was no difference observed between group A and B(χ(2)=0.646, P=0.422). In group A, tuberculosis specialized hospitals using regular doses for R was only 38.7%(12/31). After 3 years' follow-up, no-relapse-success for group A was 66.7% (10/15). Conclusions: Inappropriate individualized treatment would increase treatment failure for retreatment tuberculosis. Higher doses of H and R and prolonged extensive therapy phase could contribute to increased treatment success.
目的： 分析和评价复治肺结核单耐药和多耐药个体化治疗效果，并与标准化方案比较，探讨如何规范复治耐药肺结核个体化治疗方案。 方法： 本研究为前瞻性多中心队列研究，分析2009年7月1日至2016年8月30日国内22家结核病诊疗机构收治的复治菌阳肺结核患者254例，按分散随机方法分为3组，所有患者入组后即开始治疗。治疗3个月时根据MTB培养和药敏试验等结果，将耐多药(MDR)、广泛耐药(XDR)、非结核分枝杆菌(NTM)和涂阳培阴肺结核患者排除。个体化组86例，男性62例，女性24例，平均年龄(41±14)岁。接受个体化治疗方案，在复治标准方案[强化期2个月肌内注射链霉素(S)，口服异烟肼(H)、利福平(R)、乙胺丁醇(Z)和吡嗪酰胺(E)；继续期6个月口服异烟肼、利福平和乙胺丁醇；方案缩写为2SHRZE/6HRE]的基础上，根据药敏试验结果对其中单耐药和多耐药患者的不同耐药种类进行替换，替换后重新计算疗程，总疗程≥12个月；药敏试验没有耐药的患者不进行药物替换，继续2SHRZE/6HRE方案治疗，疗程8个月。复治组86例，男63例，女23例，平均年龄(42±14)岁。接受复治调整方案治疗：强化期4个月，在强化期的前2个月每日肌内注射链霉素，口服利福喷丁2次/w，异烟肼和乙胺丁醇1次/d，吡嗪酰胺3次/d；强化期后2个月间歇肌内注射链霉素0.75 g, 3次/w，口服利福喷丁2次/w，异烟肼和乙胺丁醇1次/d，吡嗪酰胺3次/d；继续期4个月口服利福喷丁2次/w，异烟肼和乙胺丁醇1次/d，方案缩写为2HL(2)EZS/2HL(2)EZS(3)/4HL(2)E。H剂量体重<50 kg者0.3 g/d，体重≥50 kg者0.4～0.5 g/d；L(2)剂量0.6 g，2次/w，乙胺丁醇0.75，1次/d；吡嗪酰胺0.5 g，3次/d。标化组82例，男66例，女16例，平均年龄(42±12)岁。使用国家结核病防治规划推荐的复治肺结核标准化方案，即2HREZS/6HRE。复治组和标化组对单耐药和多耐药患者不进行药物替换，总疗程均为8个月。分别比较不同组别的治疗效果，分析个体化组对多耐药患者药物替换情况，并观察根据患者体重选择H或R剂量的合理性。本研究为多中心回顾性队列研究，采用SPSS 19.0统计软件，计量资料组间比较采用方差分析(正态分布且方差齐)或秩和检验(非正态分布)。计数资料采用χ(2)检验或Fisher确切概率检验。P<0.05表示差异有统计学意义。 结果： 个体化组、复治组与标准化组的治愈率分别为73.3%(63/86)、76.7%(66/86)和50%(41/82)，治疗成功率分别为80.2%(69/86)、84.9%(73/86)与62.2%(51/82)，失败率分别为8.1%(7/86)、4.7%(4/86)与19.5%(16/82)，个体化组与复治组和标准化组比较，上述指标差异均有统计学意义(χ(2)＝13.127，P＝0.001)，但个体化组和复治组比较差异无统计学意义(χ(2)＝0.646，P＝0.422)。个体化组使用R的正规剂量在专科医院仅占38.7%(12/31)。满疗程治疗后随访3年，个体化组多耐药患者药物替换的15例中治疗成功10例。 结论： 对复治肺结核多耐药患者采取不合理的个体化治疗方案将增加治疗失败的风险。适当提高H或R剂量和适当延长强化期，可有效提高复治肺结核治疗的成功率。.
Keywords: Individualized treatment regimen; Standardized treatment regimen; Tuberculosis, pulmonary.