Inhaled antibiotics for long-term therapy in cystic fibrosis

 

Abstract

Background

Inhaled antibiotics are commonly used to treat persistent airway infection that contributes to lung damage in people with cystic fibrosis (CF).

Objectives

To examine the evidence that inhaled antibiotic treatment in people with CF reduces frequency of exacerbations of infection, and improves lung function, quality of life and survival. To examine adverse effects of inhaled antibiotic treatment.

Search methods

Trials were identified from the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register.

Last search: 31 January 2011.

Selection criteria

Trials were selected if inhaled antibiotic treatment was used for at least four weeks in people with CF, treatment allocation was randomised or quasi-randomised, and there was a control group (either placebo, no placebo or another inhaled antibiotic).

Data collection and analysis

Two authors independently selected trials, judged the risk of bias and extracted data from these trials.

Main results

The searches identified 176 citations to 78 trials. Nineteen trials, with 1724 participants, met the inclusion criteria. Adequate meta-analysis was not possible because of the variability of study design and reporting of results. Seventeen trials with 1562 participants compared an inhaled antibiotic with placebo or usual treatment for a duration between 1 and 32 months. Inhaled tobramycin was studied in eight trials. Lung function (measured as forced expired volume in one second) was higher and exacerbations of lung infection (by different measures) were less in the antibiotic-treated group. Resistance to antibiotics increased more in the antibiotic-treated group than in placebo group when results were reported. No auditory or renal impairment was found; analysis showed tinnitus, voice alteration, hemoptysis and cough were more frequent with tobramycin than placebo. One trial, compared tobramycin with colistin in 115 participants, after one month the mean difference in forced expiratory volume at one second was 6.33 (95% confidence interval -0.04 to 12.70) favouring tobramycin.

Authors' conclusions

Inhaled antibiotic treatment probably improves lung function and reduces exacerbation rate, but a pooled estimate of the level of benefit is not possible. The best evidence is for inhaled tobramycin. More evidence, from trials of longer duration, is needed to determine whether this benefit is maintained and to determine the significance of development of antibiotic-resistant organisms.

 

Plain language summary

Inhaling antibiotics to treat lung infection in people with cystic fibrosis

Cystic fibrosis is an inherited disease which results in abnormal mucus in several parts of the body. The main organ affected is the lungs which are susceptible to infection by certain bacteria, the most frequently isolated being Staphylococcus aureus and Pseudomonas aeruginosa. Infection causes inflammation that results in progressive damage to the lungs. We aimed to find out if inhaling antibiotics would reduce the effects of infection. We wanted to learn whether this treatment would improve lung function, quality of life and survival. We also looked for any adverse events. This review includes 19 trials with 1724 people. We found that inhaling an antibiotic to fight these bacteria improved lung function during the study and reduced frequency of exacerbations. However, there was more resistance to antibiotics, tinnitus and change in voice in the treatment groups. Further research is needed to show whether the benefits can be maintained in the long-term and to work out the best antibiotic to use and at what dose.

 

摘要

背景

吸入性抗綠膿桿菌抗生素在囊狀纖維化的應用

反覆性的綠膿桿菌感染，常造成囊狀纖維化患者的肺部損害，並導致患者身體嬴弱甚至死亡。吸入性抗綠膿桿菌抗生素經常應用於此類型的感染。

目標

為了解吸入性抗綠膿桿菌抗生素對囊狀纖維化患者，在減少感染惡化的發生，改善肺功能、生活品質及存活率等成效，並了解吸入性抗綠膿桿菌抗生素治療的副作用。

搜尋策略

研究資料來自Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials資料庫。並聯繫吸入性抗綠膿桿菌抗生素製造的廠商，以取得更進一步的資料。最近一次進入Group's Trials Register: 檢索的日期為2006年11月。

選擇標準

納入研究條件為以吸入性抗綠膿桿菌抗生素，治療囊狀纖維化患者四周以上，採隨機或準隨機取樣方法，以安慰劑或其他吸入性抗生素作為研究控制組進行比較。

資料收集與分析

此篇評論的初步版本，由兩位作者各自獨立的評估相關研究的合適性及研究方法的品質。由一位作者根據相關研究擷取所需資料，提供資料上的補充，並完成此篇評論。

主要結論

本研究搜索出116篇出自53組試驗的文章，其中14組試驗共1100名受試者符合條件並納入本研究分析。在13組試驗共985名受試者的試驗，是比較吸入性抗綠膿桿菌抗生素及使用安慰劑或一般常規治療的差異。其中一組試驗的受試者佔所有比例的53%；另外其中有7組試驗採用交叉試驗方法。 8組試驗以Tobramycin進行1至32個月的研究。其中9組試驗中，實驗組肺功能檢測的第一秒吐氣量(FEV1)較對照組來得佳。此外，實驗組對抗生素的抗藥性也比使用安慰劑的對照組來得高。使用tobramycin的實驗組，也比對照組較常出現耳鳴及聲音改變。在一項為期一個月的短期研究中，比較使用tobramycin及 colistin 的115位受試者，結果發現使用tobramycin在第一秒吐氣量的檢測上顯示較佳的改善。

作者結論

吸入性抗綠膿桿菌抗生素治療有助於改善肺功能，然而仍需更多長程研究的佐證，以了解已產生抗藥性的個體也能維持藥物的有效性。目前還沒有足夠的研究證據提供推薦使用的抗生素及使用劑量。

翻譯人

本摘要由臺灣大學附設醫院蕭雅慧翻譯。

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

總結

吸入性抗綠膿桿菌抗生素治療，能增進囊狀纖維化患者患者的肺功能並減少感染的次數；該症為造成身體多部位發生異常黏液的遺傳性疾病。囊狀纖維化的主要併發症為肺部疾病。肺部異常的黏液分泌，易導致肺部受到特定細菌包括綠膿桿菌的感染。由於患者肺部恆久既存的損傷，而無法經由抗生素治療根除掉細菌感染的問題。本篇經由各研究試驗的評論中發現，吸入性抗生素有助於對抗細菌進而控制住感染的情形。然而對於像是增加身體特定器官發生抗藥性等可能發生的副作用，仍需未來的研究來釐清。