吡嗪酰胺酶活性与耐多药肺结核近期临床疗效的相关性研究

Correlation between pyrazinamidase activity and the short-term clinical efficacy of multidrug-resistant pulmonary tuberculosis

目的研究吡嗪酰胺酶活性与耐多药肺结核(multidrug-resistant pulmonary tuberculosis,MDR-PTB)近期疗效的相关性,为MDR-PTB患者化学药物治疗的选择提供指导。方法采用前瞻性队列研究的方法,将广州市胸科医院2018年7月至2019年12月收治的85例MDR-PTB患者作为研究对象,均接受世界卫生组织推荐的6Am-Mfx-PZA-Pto-Cs/18Mfx-PZA-Pto-Cs(Am:阿米卡星;Mfx:莫西沙星;PZA:吡嗪酰胺;Pto:丙硫异烟胺;Cs:环丝氨酸)治疗方案。85例患者中,剔除9例丢失、中断治疗、失访患者,共76例患者纳入最终研究。以Wayne方法检测吡嗪酰胺酶的活性,以BACTEC MGIT 960方法检测吡嗪酰胺药物敏感性;比较吡嗪酰胺酶阳性患者与阴性患者治疗2、4、6个月末痰菌阴转、病灶吸收和空洞闭合情况。结果76例患者中,吡嗪酰胺酶阳性32例(42.1%),吡嗪酰胺酶阴性44例(57.9%);吡嗪酰胺表型耐药36例(47.4%),吡嗪酰胺表型敏感40例(52.6%)。吡嗪酰胺药物敏感性检测与吡嗪酰胺酶活性检测的一致性较高(Kappa=0.687,P=0.000)。吡嗪酰胺酶阳性患者治疗4个月末病灶吸收率(59.4%,19/32)及空洞闭合有效率(65.5%,19/29)均高于吡嗪酰胺酶阴性患者[分别为36.4%(16/44)和36.8%(14/38)],差异均有统计学意义(χ^(2)=3.949,P=0.047;χ^(2)=5.411,P=0.020)。吡嗪酰胺酶阳性患者治疗6个月后的空洞闭合有效率(86.2%,25/29)高于吡嗪酰胺酶阴性患者(63.2%,24/38),差异有统计学意义(χ^(2)=4.447,P=0.035)。结论MDR-PTB患者的疗效与吡嗪酰胺酶活性有关,吡嗪酰胺酶阳性患者应用含吡嗪酰胺的MDR-PTB标准方案治疗后,病灶吸收及空洞闭合的效果优于吡嗪酰胺酶阴性患者。

Objective To explore the correlation between pyrazinamidase(PZase)activity and the short-term efficacy of multidrug-resistant pulmonary tuberculosis(MDR-PTB),and to provide guidance for the choice of chemotherapy for MDR-PTB patients.Methods A prospective cohort study was conducted on 85 MDR-PTB patients admitted to Guangzhou Chest Hospital from July 2018 to December 2019.All the patients received 6Am-Mfx-PZA-Pto-Cs/18Mfx-PZA-Pto-Cs(Am:amikacin;Mfx:moxifloxacin;PZA:pyrazinamide;Pto:protionamide;Cs:cycloserine)regimen recommended by WHO.Of the 85 MDR-PTB patients,9 patients were excluded,including those who lost,interrupted treatment or lost to follow-up,and 76 patients were included in the final study.Wayne method was used to detect PZase activity,and BACTEC MGIT 960 system was used to detect the drug sensitivity to PZA.The sputum negative conversion,lesion absorption and cavity closure in patients positive or negative for PZase at the end of 2,4 and 6 months after treatment were compared.Results Of the 76 patients,PZase was positive in 32 cases(42.1%)and negative in 44 cases(57.9%);36 cases(47.4%)PZA were with phenotypic resistance and 40 cases(52.6%)were with PZA phenotypic sensitivity.High consistency was found between PZA drug sensitivity test and PZase activity test(Kappa=0.687,P=0.000).At the end of the 4th month of the treatment,the lesion absorption rate in PZase-positive patients were significantly higher than those in PZase-negative patients(59.4%(19/32)vs 36.4%(16/44),χ^(2)=3.949,P=0.047;65.5%(19/29)vs 36.8%(14/38),χ^(2)=5.411,P=0.020).After 6-month treatment,the effective rate of cavity closure in PZase-positive patients was significantly higher than that in PZase-negative patients(86.2%(25/29)vs 63.2%(24/38),χ^(2)=4.447,P=0.035).Conclusion The efficacy of MDR-PTB patients is related to PZase activity.The effect of lesion absorption and cavity closure in PZase-positive patients treated with standard regimen of MDR-PTB containing PZA is better than that in PZase-negative patients.