Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
PLoS One. 2012;7(1):e30194. doi: 10.1371/journal.pone.0030194. Epub 2012 Jan 17.
The optimal treatment for latent multiple-drug resistant tuberculosis infection remains unclear. In anticipation of future clinical trials, we modeled the expected performance of six potential regimens for treatment of latent multiple-drug resistant tuberculosis.
A computerized Markov model to analyze the total cost of treatment for six different regimens: Pyrazinamide/ethambutol, moxifloxacin monotherapy, moxifloxacin/pyrazinamide, moxifloxacin/ethambutol, moxifloxacin/ethionamide, and moxifloxacin/PA-824. Efficacy estimates were extrapolated from mouse models and examined over a wide range of assumptions.
In the base-case, moxifloxacin monotherapy was the lowest cost strategy, but moxifloxacin/ethambutol was cost-effective at an incremental cost-effectiveness ratio of $21,252 per quality-adjusted life-year. Both pyrazinamide-containing regimens were dominated due to their toxicity. A hypothetical regimen of low toxicity and even modest efficacy was cost-effective compared to "no treatment."
In our model, moxifloxacin/ethambutol was the preferred treatment strategy under a wide range of assumptions; pyrazinamide-containing regimens fared poorly because of high rates of toxicity. Although more data are needed on efficacy of treatments for latent MDR-TB infection, data on toxicity and treatment discontinuation, which are easier to obtain, could have a substantial impact on public health practice.
潜伏性耐多药结核病感染的最佳治疗方法仍不清楚。为了未来的临床试验，我们建立了 6 种潜在治疗方案治疗潜伏性耐多药结核病的预期表现模型。
使用计算机化的 Markov 模型来分析 6 种不同方案（吡嗪酰胺/乙胺丁醇、莫西沙星单药治疗、莫西沙星/吡嗪酰胺、莫西沙星/乙胺丁醇、莫西沙星/乙硫异烟胺、莫西沙星/PA-824）的总治疗费用。疗效估计值从小鼠模型中推断得出，并在广泛的假设范围内进行了检查。
在基本情况下，莫西沙星单药治疗是成本最低的策略，但莫西沙星/乙胺丁醇的增量成本效益比为每质量调整生命年 21252 美元，具有成本效益。由于毒性问题，含吡嗪酰胺的方案均被排除。与“不治疗”相比，假设的低毒性甚至疗效中等的方案具有成本效益。
在我们的模型中，在广泛的假设条件下，莫西沙星/乙胺丁醇是首选的治疗方案；由于毒性高，含吡嗪酰胺的方案表现不佳。尽管潜伏性耐多药结核病感染治疗效果的数据需求量较大，但更容易获得的毒性和治疗中断数据可能对公共卫生实践产生重大影响。
