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标准抗菌药敏试验与生物膜抗菌药敏试验用于指导囊性纤维化患者的抗生素治疗

Standard versus biofilm antimicrobial susceptibility testing to guide antibiotic therapy in cystic fibrosis.

作者信息

Waters Valerie, Ratjen Felix

机构信息

Department of Pediatrics, Division of Infectious Diseases, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada, M5G 1X8.

出版信息

Cochrane Database Syst Rev. 2017 Oct 5;10(10):CD009528. doi: 10.1002/14651858.CD009528.pub4.

Abstract

BACKGROUND

The antibiotics used to treat pulmonary infections in people with cystic fibrosis are typically chosen based on the results of antimicrobial susceptibility testing performed on bacteria traditionally grown in a planktonic mode (grown in a liquid). However, there is considerable evidence to suggest that Pseudomonas aeruginosa actually grows in a biofilm (or slime layer) in the airways of people with cystic fibrosis with chronic pulmonary infections. Therefore, choosing antibiotics based on biofilm rather than conventional antimicrobial susceptibility testing could potentially improve response to treatment of Pseudomonas aeruginosa in people with cystic fibrosis. This is an update of a previously published Cochrane Review.

OBJECTIVES

To compare biofilm antimicrobial susceptibility testing-driven therapy to conventional antimicrobial susceptibility testing-driven therapy in the treatment of Pseudomonas aeruginosa infection in people with cystic fibrosis.

SEARCH METHODS

We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Most recent search: 19 June 2017.We also searched two ongoing trials registries and the reference lists of relevant articles and reviews. Most recent searches: 24 August 2017 and 05 September 2017.

SELECTION CRITERIA

Randomized controlled trials of antibiotic therapy based on biofilm antimicrobial susceptibility testing compared to antibiotic therapy based on conventional antimicrobial susceptibility testing in the treatment of Pseudomonas aeruginosa pulmonary infection in people with cystic fibrosis.

DATA COLLECTION AND ANALYSIS

Both authors independently selected trials, assessed their risk of bias and extracted data from eligible trials. Additionally, the review authors contacted the trial investigators to obtain further information. The quality of the evidence was assessed using the GRADE criteria.

MAIN RESULTS

The searches identified two multicentre, randomized, double-blind controlled clinical trials eligible for inclusion in the review with a total of 78 participants (adults and children); one trial was done in people who were clinically stable, the other in people experiencing pulmonary exacerbations. These trials prospectively assessed whether the use of biofilm antimicrobial susceptibility testing improved microbiological and clinical outcomes in participants with cystic fibrosis who were infected with Pseudomonas aeruginosa. The primary outcome was the change in sputum Pseudomonas aeruginosa density from the beginning to the end of antibiotic therapy.Although the intervention was shown to be safe, the data from these two trials did not provide evidence that biofilm susceptibility testing was superior to conventional susceptibility testing either in terms of microbiological or lung function outcomes. One of the trials also measured risk and time to subsequent exacerbation as well as quality of life measures and did not demonstrate any difference between groups in these outcomes. Both trials had an overall low risk of bias and the quality of the evidence using GRADE criteria was deemed to be moderate to high for the outcomes selected.

AUTHORS' CONCLUSIONS: The current evidence is insufficient to recommend choosing antibiotics based on biofilm antimicrobial susceptibility testing rather than conventional antimicrobial susceptibility testing in the treatment of Pseudomonas aeruginosa pulmonary infections in people with cystic fibrosis. Biofilm antimicrobial susceptibility testing may be more appropriate in the development of newer, more effective formulations of drugs which can then be tested in clinical trials.

摘要

背景

用于治疗囊性纤维化患者肺部感染的抗生素通常是根据对以浮游模式(在液体中生长)传统培养的细菌进行的抗菌药敏试验结果来选择的。然而,有大量证据表明,在患有慢性肺部感染的囊性纤维化患者气道中,铜绿假单胞菌实际上是以生物膜(或黏液层)的形式生长的。因此,基于生物膜而非传统抗菌药敏试验来选择抗生素,可能会改善囊性纤维化患者对铜绿假单胞菌感染的治疗反应。这是对先前发表的Cochrane系统评价的更新。

目的

比较生物膜抗菌药敏试验驱动的治疗与传统抗菌药敏试验驱动的治疗在囊性纤维化患者铜绿假单胞菌感染治疗中的效果。

检索方法

我们检索了Cochrane囊性纤维化试验注册库,该注册库通过电子数据库检索以及对期刊和会议摘要书籍的手工检索编制而成。最近一次检索时间为2017年6月19日。我们还检索了两个正在进行的试验注册库以及相关文章和综述的参考文献列表。最近一次检索时间分别为2017年8月24日和2017年9月5日。

入选标准

在囊性纤维化患者铜绿假单胞菌肺部感染治疗中,基于生物膜抗菌药敏试验的抗生素治疗与基于传统抗菌药敏试验的抗生素治疗的随机对照试验。

数据收集与分析

两位作者独立选择试验,评估其偏倚风险,并从符合条件的试验中提取数据。此外,综述作者联系试验研究者以获取更多信息。使用GRADE标准评估证据质量。

主要结果

检索到两项多中心、随机、双盲对照临床试验符合纳入本综述的条件,共有78名参与者(成人和儿童);一项试验针对临床稳定的患者,另一项针对肺部病情加重的患者。这些试验前瞻性地评估了使用生物膜抗菌药敏试验是否能改善感染铜绿假单胞菌的囊性纤维化参与者的微生物学和临床结局。主要结局是抗生素治疗开始至结束时痰中铜绿假单胞菌密度的变化。尽管该干预措施被证明是安全的,但这两项试验的数据并未提供证据表明生物膜药敏试验在微生物学或肺功能结局方面优于传统药敏试验。其中一项试验还测量了后续病情加重的风险和时间以及生活质量指标,并未显示两组在这些结局上有任何差异。两项试验总体偏倚风险较低,对于所选结局,使用GRADE标准评估的证据质量被认为是中等到高。

作者结论

目前的证据不足以推荐在囊性纤维化患者铜绿假单胞菌肺部感染治疗中基于生物膜抗菌药敏试验而非传统抗菌药敏试验来选择抗生素。生物膜抗菌药敏试验可能更适合用于开发更新、更有效的药物制剂,然后在临床试验中进行测试。

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Standard versus biofilm antimicrobial susceptibility testing to guide antibiotic therapy in cystic fibrosis.
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