Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis

 

Abstract

Background

Lower respiratory tract infection with Pseudomonas aeruginosa occurs in most people with cystic fibrosis (CF). Once chronic infection is established, Pseudomonas aeruginosa is virtually impossible to eradicate and is associated with increased mortality and morbidity. Early infection may be easier to eradicate.

Objectives

To determine whether antibiotic treatment of early Pseudomonas aeruginosa infection in children and adults with CF eradicates the organism, improves clinical and microbiological outcome and is superior to or more cost-effective than other strategies.

Search methods

We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.

Most recent search: 11 December 2008.

Selection criteria

We included randomised controlled trials (RCTs) of people with CF, in whom Pseudomonas aeruginosa had recently been isolated from respiratory secretions. We compared combinations of inhaled, oral or intravenous antibiotics with placebo, usual treatment or other combinations of inhaled, oral or intravenous antibiotics. We excluded non-randomised trials, cross-over trials, and those utilising historical controls.

Data collection and analysis

Both authors independently selected trials, assessed methodological quality and extracted data.

Main results

The search identified 25 trials. Four trials (95 participants) were eligible for inclusion; two trials are ongoing. Evidence from two trials showed treatment of early Pseudomonas aeruginosa infection with inhaled tobramycin results in microbiological eradication of the organism from respiratory secretions more often than placebo, OR 0.15 (95% CI 0.03 to 0.65) and that this effect may persist for up to 12 months. These trials were of low methodological quality.

The only identified RCT of oral ciprofloxacin and nebulised colistin versus usual treatment was of poor methodological quality. Results suggested treatment of early infection results in microbiological eradication of Pseudomonas aeruginosa more often than usual treatment, after two years, OR 0.24 (95% CI 0.06 to 0.96). There is insufficient evidence to determine whether antibiotic strategies for the eradication of early Pseudomonas aeruginosa decrease mortality or morbidity, improve quality of life, or are associated with adverse effects compared to placebo or standard treatment.

Authors' conclusions

We found that nebulised antibiotics, alone or in combination with oral antibiotics, were better than no treatment for early infection with Pseudomonas aeruginosa. Eradication may be sustained in the short term. Overall, there is insufficient evidence from this review to state which antibiotic strategy should be used for the eradication of early Pseudomonas aeruginosa infection in CF.

 

Plain language summary

Different ways of giving antibiotics to remove Pseudomonas aeruginosa infection in people with CF

Cystic fibrosis is an inherited condition where the airways frequently become blocked with mucus, often associated with respiratory infections. These infections may lead to progressive respiratory failure and death from breathing failure. A germ called Pseudomonas aeruginosa is a frequent cause of infection. We wanted to compare different combinations of inhaled, oral and intravenous antibiotics. There are four trials included in the review. Two trials are still ongoing. We found that when treating early infection, nebulised antibiotics were better than no treatment in eliminating the germ in most people. This was also true for a combination of nebulised and oral antibiotics. The trials had quite a short follow-up period. Therefore, we could not show whether treatment made people with cystic fibrosis feel better or live longer. Further research is needed to see whether removing the germ completely improves the well-being and quality of life in people with cystic fibrosis. There have not yet been satisfactory trials comparing outcomes for people with cystic fibrosis treated with oral or intravenous antibiotics.

 

摘要

背景

根除囊狀纖維化病人綠膿桿菌感染的抗生素使用策略

大部分囊性纖維化病人都會發生綠膿桿菌下呼吸道感染。一旦造成慢性感染，幾乎很難根除，連帶造成死亡率與患病率的上升。早期的感染比較容易根除。

目標

評估抗生素是否能清除囊性纖維化病人早期綠膿桿菌的感染，並且改善預後。

搜尋策略

我們搜尋了Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register 資料庫；其中包含了由綜合的電子資料庫和手動搜尋相關期刊所挑選出的參考文獻，以及相關研討會摘要。 最近一次的搜尋:2006年9月。

選擇標準

我們收納最近由呼吸道分泌物培養出綠膿桿菌感染的囊性纖維化病人之隨機對照試驗。我們比較吸入、口服或靜脈注射抗生素與安慰劑或常規治療，或其它吸入性、口服或靜脈注射抗生素組合之比較。我們排除非隨機對照試驗，交叉試驗，以及使用歷史對照組的試驗。

資料收集與分析

兩位作者皆獨立評估試驗及方法，並擷取數據。

主要結論

我們總共收納了19個臨床試驗，其中3個可適用，2個正在進行中。其中2個臨床試驗發現對於根除早期綠膿桿菌的感染，吸入性的tobramycin比起安慰劑有效，OR 0.15 (95% CI 0.03 to 0.65)，根除的效果可以持續至少12個月。但是這些臨床試驗方法學品質不高。其中有一個隨機對照試驗發現口服 ciprofloxacin 及 氣霧式噴劑colisitin相較普通的治療方法，兩年的期間內，有更高的根除機率，OR 0.24 (95% CI 0.06 to 0.96)，並沒有足夠的證據顯示是否抗生素的治療策略對於早期根除綠膿桿菌降低死亡率、患病率、改善生活品質，或是相較於安慰劑或標準治療方式與不良反應較有關連。

作者結論

我們發現對於綠膿桿菌的早期感染，氣霧式噴劑抗生素單獨或合併使用口服抗生素比起不治療是有益處的。能夠在短期間內維持根除感染的狀態。但是總體而言，對於這個抗生素使用方法仍沒有充分的證據。

翻譯人

本摘要由臺灣大學附設醫院李咏馨翻譯。

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

總結

氣霧式噴劑抗生素(有或是沒有合併口服抗生素)對於囊性纖維化病人綠膿桿菌感染，可能可以根除感染，延緩慢性感染病患黏液阻塞肺部而造成呼吸道感染。囊性纖維化病人因為呼吸道被黏液阻塞，經常造成呼吸道的感染，甚至可能造成呼吸衰竭以致於死亡。一種叫做Pseudomonas aeruginosa 是一種很常見的感染源，我們發現氣霧式噴劑抗生素(或是合併口服抗生素)對於囊性纖維化病人的早期此菌的感染，比沒有治療還要好，能夠根除大部分病人的感染。但是這些臨床試驗的追蹤時間相對而言較短，而且對於生命的延長以及生活品質的提升還待更進一步的研究。