Chien Jung-Yien, Chien Shun-Tien, Chiu Wei-Yih, Yu Chong-Jen, Hsueh Po-Ren
Graduate Institute of Clinical Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan Chest Hospital, Ministry of Health and Welfare, Tainan, Taiwan.
Chest Hospital, Ministry of Health and Welfare, Tainan, Taiwan.
Antimicrob Agents Chemother. 2016 Jul 22;60(8):4708-16. doi: 10.1128/AAC.00425-16. Print 2016 Aug.
It is unclear whether the use of moxifloxacin (MFX), a newer synthetic fluoroquinolone, results in better outcomes in patients with ofloxacin (OFX)-resistant multidrug-resistant tuberculosis (MDR-TB). During the period from April 2006 to December 2013, a total of 2,511 patients with culture-confirmed tuberculosis (TB) were treated at a TB referral hospital in southern Taiwan. Of the 2,511 patients, 325 (12.9%) had MDR-TB, and of those 325 patients, 81 (24.9%) had OFX-resistant MDR-TB and were included in the study. Among the 81 patients with OFX-resistant MDR-TB, 50 (61.7%) were successfully treated and 31 (38.3%) had unfavorable outcomes, including treatment failure (n = 25; 30.9%), loss to follow-up (n = 2; 2.5%), and death (n = 4; 4.9%). Patients treated with MFX had a significantly higher rate of treatment success (77.3% versus 43.2%; odds ratio [OR] = 4.46, 95% confidence interval [CI] = 1.710 to 11.646, P = 0.002) than patients not treated with MFX, especially among those infected with MFX-susceptible isolates (40.7%) or isolates with low-level resistance to MFX (28.4%). Multivariate logistic regression analysis showed that treatment with MFX (adjusted odds ratio = 6.54, 95% CI = 1.44 to 29.59, P = 0.015) was the only independent factor associated with treatment success. Mutation at codon 94 in the gyrA gene was the most frequent mutation (68.0%) associated with high-level MFX resistance. Multivariate Cox proportional hazards regression analysis showed that treatment with MFX was also an independent factor associated with early culture conversion (hazard ratio = 3.12, 95% CI = 1.48 to 6.54, P = 0.003). Our results show that a significant proportion of OFX-resistant MDR-TB isolates were susceptible or had low-level resistance to MFX, indicating that patients with OFX-resistant MDR-TB benefit from treatment with MFX.
新型合成氟喹诺酮类药物莫西沙星（MFX）用于治疗对氧氟沙星（OFX）耐药的耐多药结核病（MDR-TB）患者是否能带来更好的疗效尚不清楚。在2006年4月至2013年12月期间，台湾南部一家结核病转诊医院共治疗了2511例经培养确诊的结核病（TB）患者。在这2511例患者中，325例（12.9%）患有MDR-TB，在这325例患者中，81例（24.9%）患有对OFX耐药的MDR-TB并被纳入研究。在81例对OFX耐药的MDR-TB患者中，50例（61.7%）成功治愈，31例（38.3%）治疗结果不佳，包括治疗失败（25例；30.9%）、失访（2例；2.5%）和死亡（4例；4.9%）。接受MFX治疗的患者治疗成功率（77.3%对43.2%；优势比[OR]=4.46，95%置信区间[CI]=1.710至11.646，P=0.002）显著高于未接受MFX治疗的患者，尤其是在感染对MFX敏感菌株（40.7%）或对MFX低水平耐药菌株（28.4%）的患者中。多因素逻辑回归分析显示，MFX治疗（调整后优势比=6.54，95%CI=1.44至29.59，P=0.015）是与治疗成功相关的唯一独立因素。gyrA基因94位密码子突变是与高水平MFX耐药相关的最常见突变（68.0%）。多因素Cox比例风险回归分析显示，MFX治疗也是与早期培养转阴相关的独立因素（风险比=3.12，95%CI=1.48至6.54，P=0.003）。我们的结果表明，相当一部分对OFX耐药的MDR-TB菌株对MFX敏感或低水平耐药，这表明对OFX耐药的MDR-TB患者可从MFX治疗中获益。
