Marra Fawziah, Marra Carlo A, Moadebi Susanne, Shi Peilin, Elwood R Kevin, Stark Greg, FitzGerald J Mark
University of British Columbia, Vancouver, BC, Canada.
Chest. 2005 Sep;128(3):1406-13. doi: 10.1378/chest.128.3.1406.
Fluoroquinolones are commonly used in the treatment of tuberculosis (TB) for drug-sensitive patients who are intolerant to first-line antituberculous agents or who are infected with drug-resistant organisms. Despite increasing use of these agents, there is little information on their tolerance outside of clinical trial settings.
To compare overall rate of major adverse events associated with levofloxacin-containing regimen to standard therapy.
Cases (levofloxacin-containing regimen) were matched by age and sex to their control subjects (standard first-line TB drugs). Eligible patients were identified from the provincial TB database from 2001 to 2004. Drug safety was assessed by evaluation of the nature of the adverse event, the likelihood of association with the study medications, and severity. Only major side effects, that is, those who had a severe or moderate adverse event that was categorized to be definitely, probably, or possibly related to the TB medications, were considered for the analysis.
During the 3-year study period, 102 patients received levofloxacin, and 358 patients received first-line agents for treatment of active TB. There were no significant differences between the two groups except for indication (82% of patients in the levofloxacin group had an antecedent adverse event to first-line TB drugs, whereas 18% received levofloxacin because of resistance) and concurrent use of first-line drugs (majority of patients in the levofloxacin arm were not receiving concurrent isoniazid or rifampin). The rate of any major adverse event was almost half among those using levofloxacin as among those on standard therapies (rate ratio, 0.60; 95% confidence interval [CI], 0.44 to 0.82). After adjustment for the differences in exposure of concomitant medications, the rate of any major adverse event was similar between the levofloxacin and control arms (adjusted rate ratio, 0.83; 95% CI, 0.66 to 1.03). Furthermore, there was no difference between the levofloxacin and control arms with respect to CNS (adjusted rate ratio, 0.94; 95% CI, 0.61 to 1.43), GI tract (adjusted rate ratio, 0.81; 95% CI, 0.58 to 1.13), skin (adjusted rate ratio, 0.65; 95% CI, 0.38 to 1.10), or musculoskeletal (MSK) [adjusted rate ratio, 0.87; 95% CI, 0.48 to 1.60] related adverse events when adjusted for concomitant drugs. The results of the secondary analysis for the rate of major adverse events within the first 100 days were similar to the primary analysis. The time to the first major adverse event was similar between the levofloxacin group and the control group (adjusted hazards ratio, 1.01; 95% CI, 0.76 to 1.34).
Concomitant use of a levofloxacin-containing regimen resulted in a similar rate of adverse events compared with conventional first-line regimens when used for treatment of active TB, despite a history of adverse events.
氟喹诺酮类药物常用于治疗对一线抗结核药物不耐受或感染耐药菌的药物敏感型结核病（TB）患者。尽管这些药物的使用日益增加，但在临床试验环境之外，关于其耐受性的信息却很少。
比较含左氧氟沙星方案与标准治疗相关的主要不良事件总体发生率。
病例（含左氧氟沙星方案）按年龄和性别与对照受试者（标准一线抗结核药物）匹配。从2001年至2004年的省级结核病数据库中识别符合条件的患者。通过评估不良事件的性质、与研究药物关联的可能性以及严重程度来评估药物安全性。仅分析主要副作用，即那些发生严重或中度不良事件且被归类为肯定、很可能或可能与抗结核药物相关的事件。
在3年的研究期间，102例患者接受了左氧氟沙星治疗，358例患者接受一线药物治疗活动性结核病。除了适应证（左氧氟沙星组82%的患者有一线抗结核药物的既往不良事件，而18%因耐药接受左氧氟沙星治疗）和一线药物的联合使用情况（左氧氟沙星组的大多数患者未同时使用异烟肼或利福平）外，两组之间没有显著差异。使用左氧氟沙星的患者发生任何主要不良事件的发生率几乎是接受标准治疗患者的一半（率比，0.60；95%置信区间[CI]，0.44至0.82）。在调整了伴随药物暴露的差异后，左氧氟沙星组和对照组发生任何主要不良事件的发生率相似（调整后的率比，0.83；95%CI，0.66至1.03）。此外，在调整了伴随药物后，左氧氟沙星组和对照组在中枢神经系统（调整后的率比，0.94；95%CI，0.61至1.43）、胃肠道（调整后的率比，0.81；95%CI，0.58至1.13）、皮肤（调整后的率比，0.65；95%CI，0.38至1.10）或肌肉骨骼（MSK）[调整后的率比，0.87；95%CI，0.48至1.60]相关不良事件方面没有差异。前100天内主要不良事件发生率的二次分析结果与初次分析相似。左氧氟沙星组和对照组首次发生主要不良事件的时间相似（调整后的风险比，1.01；95%CI，0.76至1.34）。
尽管有不良事件史，但含左氧氟沙星方案与传统一线方案用于治疗活动性结核病时，不良事件发生率相似。
