Fluoroquinolones for treating tuberculosis

 

Abstract

Background

Fluoroquinolones are sometimes used to treat multiple-drug-resistant and drug-sensitive tuberculosis. The effects of fluoroquinolones in tuberculosis regimens need to be assessed.

Objectives

To assess fluoroquinolones as additional or substitute components to antituberculous drug regimens for drug-sensitive and drug-resistant tuberculosis.

Search methods

In July 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 3), MEDLINE, EMBASE, LILACS, Science Citation Index, Database of Russian Publications, and metaRegister of Controlled Trials. We also scanned reference lists of all identified studies and contacted researchers.

Selection criteria

Randomized controlled trials of antituberculous regimens containing fluoroquinolones in people diagnosed with bacteriologically positive (sputum smear or culture) pulmonary tuberculosis.

Data collection and analysis

Two authors independently applied inclusion criteria, assessed the risk of bias in the trials, and extracted data. We used risk ratio (RR) for dichotomous data, mean difference (MD) for continuous data (both with 95% confidence intervals (CI)), and the random-effects model if we detected heterogeneity and it was appropriate to combine data.

Main results

Eleven trials (1514 participants) met the inclusion criteria. No statistically significant difference was found in trials substituting ciprofloxacin, ofloxacin or moxifloxacin for first-line drugs in relation to cure (416 participants, 3 trials), treatment failure (388 participants, 3 trials), or clinical or radiological improvement (216 participants, 2 trials). Substituting ciprofloxacin into first-line regimens in drug-sensitive tuberculosis led to a higher incidence of relapse (RR 7.17, 95% CI 1.33 to 38.58; 384 participants, 3 trials) and longer time to sputum culture conversion (MD 0.50 months, 95% CI 0.18 to 0.82; 168 participants, 1 trial), although this was confined to HIV-positive participants. Substituting for ethambutol in first-line regimens led to a higher incidence of total number of adverse events (RR 1.34, 95% CI 1.05 to 1.72; 492 participants, 2 trials). Adding or substituting levofloxacin to basic regimens in drug-resistant areas had no effect. A comparison of sparfloxacin versus ofloxacin added to regimens showed no statistically significant difference in cure (184 participants, 2 trials), treatment failure (149 participants, 2 trials), or the total number of adverse events (253 participants, 3 trials).

Authors' conclusions

Only ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin and moxifloxacin have been tested in randomized controlled trials for treating tuberculosis. We cannot recommend ciprofloxacin in treating tuberculosis. Trials of newer fluoroquinolones for treating tuberculosis are needed and are ongoing. No difference has been demonstrated between sparfloxacin and ofloxacin in drug-resistant tuberculosis.

 

Plain language summary

Substituting or adding fluoroquinolones to established first-line antituberculous drug regimens gives no additional benefit or risks

Fluoroquinolones have antituberculous activity, but are not one of the standard antituberculous medicines. Ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin, and moxifloxacin have been tested in randomized controlled trials. Ciprofloxacin should not be used as a substitute drug in the standard antituberculous regimen as more people with drug-sensitive tuberculosis had relapses and it took longer for them to be cured. However, it was no different in terms of cure or number of adverse events. Sparfloxacin was no better than ofloxacin when added to antituberculous regimens in drug-resistant tuberculosis. Further trials are warranted.

 

摘要

背景

Fluoroquinolones於結核病(tuberculosis)治療評估

Fluoroquinolones有時應用於治療多重抗藥性及藥物敏感的結核病治療。所以，Fluoroquinolones在結核病療效是需要被評估的。

目標

本研究目的主要評估對多重抗藥性及藥物敏感的結核病患者，其所使用的抗結核藥物，Fluoroquinolones是屬於添加性成分或取代性成份性質。

搜尋策略

2007年7月,我們搜尋登錄為Cochrane Infectious Diseases病例，自CENTRAL、MEDLINE、EMBASE、LILACS、Science Citation Index、俄羅斯文獻資料以及進行中的臨床試驗等資料庫，搜羅所有參考報告，並與相關研究學者接洽。

選擇標準

研究標的選擇:隨機選取經由痰抹片或細菌培養結果為陽性、診斷為結核病患者。進行抗結核藥物含有Fluoroquinolones成分之臨床試驗。

資料收集與分析

有兩位作者採取條件篩選，已受認同之評估方法來蒐集資料。我們針對兩極化數據採相對危險性法(relative risk；RR)，針對連續性數據則採平均體重差異法(weighted mean difference；WMD)來評估。兩方法均須評估95%信賴區間(confidence intervals；CI)，若得到異質性數據，則將數據合併後，以randomeffects model來評估。

主要結論

共計11個臨床試驗，達1514人次符合篩選標準，由臨床試驗數據顯示，以Ciprofloxacin、ofloxacin與moxifloxacin藥物取代第一線用藥，病患可痊癒(3個臨床試驗，416人次)，治療失敗(3個臨床試驗，388人次)，臨床或放射結果改善(2個臨床試驗，216人次)，彼此無統計上差異存在。但對藥物敏感的結核患者，以Ciprofloxacin藥物取代第一線用藥，則導致復發之發生率增高(相對危險7.17，95%信賴區間1.33 – 38.58；384人次，3臨床試驗)及長時間痰液培養的轉變。(平均體重差異0.50月，95%信賴區間0.18 – 0.82；168人次，1臨床試驗)，雖然後來證實為HIV陽性患者。但以ethambutol藥物取代第一線用藥，則導致不良之發生率增高(相對危險1.34，95%信賴區間1.05 – 1.72; 492人次，2臨床試驗)及長時間痰液培養的轉變。(平均體重差異0.50月，95%信賴區間0.18 – 0.82；168人次，1臨床試驗)，後來被證實為HIV陽性患者。其他如以levofloxacin藥物添加或取代第一線用藥結構之抗藥區則沒有反應，以sparfloxacin與ofloxacin藥物添加第一線用藥，病患可痊癒(2個臨床試驗，184人次)，治療失敗(2個臨床試驗，149人次)或發生不良者(3個臨床試驗，253人次)，彼此無統計上差異存在。

作者結論

針對結核病之隨機臨床試驗，只進行ciprofloxacin、ofloxacin、levofloxacin、sparfloxacin與moxifloxacin等藥物測試，我們無法證實ciprofloxacin治療效果，所以執行fluoroquinolones臨床試驗是必需持續進行的。sparfloxacin與ofloxacin兩種藥物在抗藥性結核病例之治療效果則無明顯差異。

翻譯人

本摘要由三軍總醫院樊修龍翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

在建立第一線結核病治療藥物投與上，fluoroquinolones的取代或添加並沒有額外的好處或風險。Fluoroquinolones雖具有抗結核活性，但是不屬於抗結核的標準治療藥物。在本臨床試驗，同樣測試Ciprofloxacin、ofloxacin、levofloxacin、sparfloxacin與moxifloxacin效果。對藥物敏感之結核病復發或似乎需要長療程的患者來說，Ciprofloxacin不應該當作標準抗結核治療藥物之取代性藥物。然而，在某些療程或不良反應是沒有差異的。添加Sparfloxacin在抗藥性結核患者的治療藥物中，其效果沒有ofloxacin佳，進一步的臨床試驗是必需的。