Empiric antibiotic coverage of atypical pathogens for community-acquired pneumonia in hospitalized adults

 

Abstract

Background

Community acquired pneumonia (CAP) is caused by various pathogens, traditionally divided into 'typical' and 'atypical'. Initial antibiotic treatment of CAP is usually empirical, customarily covering both typical and atypical pathogens. To date, no sufficient evidence exists to support this broad coverage, while limiting coverage is bound to reduce toxicity, resistance and expense.

Objectives

To assess the efficacy and need of adding antibiotic coverage for atypical pathogens in hospitalized patients with CAP, in terms of mortality and successful treatment.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, issue 1) which includes the Acute Respiratory Infection Group's specialized register; MEDLINE (January 1966 to March 2007); and EMBASE (January 1980 to January 2007).

Selection criteria

Randomized trials of adult patients hospitalized due to CAP, comparing antibiotic regimens with atypical antibiotic coverage to a regimen without atypical antibiotic coverage.

Data collection and analysis

Two review authors independently appraised the quality of each trial and extracted the data from included trials. Relative risks (RR) with 95% confidence intervals (CI) were estimated, assuming an intention-to-treat (ITT) basis for the outcome measures.

Main results

Twenty five trials were included, encompassing 5244 randomized patients. There was no difference in mortality between the atypical arm and the non-atypical arm (RR 1.15; 95% CI 0.85 to 1.56). The atypical arm showed an insignificant trend toward clinical success and a significant advantage to bacteriological eradication, which disappeared when evaluating methodologically high-quality studies alone. Clinical success for the atypical arm was significantly higher for Legionella pneumophilae (L. pneumophilae) and non-significantly lower for pneumococcal pneumonia. There was no significant difference between the groups in the frequency of (total) adverse events, or those requiring discontinuation of treatment. However, gastrointestinal events were more common in the non-atypical arm (RR 0.73, 95% CI 0.54 to 0.99). All but two included trials compared a single atypical antibiotic to a beta-lactam, while no trials assessing the addition of an atypical antibiotic to a beta-lactam were identified.

Authors' conclusions

No benefit of survival or clinical efficacy was shown to empirical atypical coverage in hospitalized patients with CAP. This conclusion relates mostly to the comparison of quinolone monotherapy to beta-lactams (BL) or cephalosporins. Further trials, comparing BL or cephalosporins therapy to BL or cephalosporins combined with a macrolide in this population, using mortality as its primary outcome, should be performed.

 

Plain language summary

Initial antibiotic treatment for coverage of 'atypical' pathogens for community-acquired pneumonia in hospitalized adults

Agents which cause pneumonia are traditionally divided into 'typical' and 'atypical', each dictating a distinct antibiotic treatment. Atypical agents refer to certain bacteria - namely, Legionella pneumophila (L. pneumophila), Mycoplasma pneumoniae (M. pneumoniae), and Chlamydia pneumoniae (C. pneumoniae). At presentation the causative agent is usually unknown so the initial treatment is empirical, customarily covering both groups. While typical coverage is essential, due to the common 'typical' pathogen Streptococcus pneumoniae (S. pneumoniae), the necessity of the atypical coverage has not been proven. This study reviewed trials comparing antibiotic regimens with atypical coverage to those without, limited to hospitalized adults with community-acquired pneumonia. Twenty five trials were included, encompassing 5244 patients. For the regimens tested, no advantage was found for regimens covering atypical pathogens in the major outcomes tested - clinical efficacy or mortality.

 

摘要

背景

對患有社區型肺炎的住院成人，經驗性投與抗非典型病原菌之廣效型抗生素的效果分析

能引發社區型肺炎(Community acquired pneumonia，CAP) 的病原菌種類相當地多，而根據病原菌的不同，可進一步區分為「典型」與「非典型」肺炎；一般通常用經驗性抗生素來治療CAP，以同時]涵蓋典型與非典型病原菌。然而，現今卻缺乏足夠的證據來支持這種廣效性的抗生素療法；相對來說，窄效的抗生素選擇應更可減少毒性、抗藥性以及與藥費的支出。

目標

藉由死亡率與治療成功率的分析，來評估廣效性抗生素(同時涵蓋典型與非典型病原菌) 用於治療患有CAP的住院病人之效果與必要性。

搜尋策略

我們搜尋了Cochrane Central Register of Controlled Clinical Trials (CENTRAL) (The Cochrane Library 2007, issue 1)，其中包含了Cochrane Acute Respiratory Infection Group's Specialised Register、MEDLINE(1966年1月至2007年3月)，以及EMBASE (1980年1月至2007年1月)。

選擇標準

我們收錄了比較能與不能涵蓋非典型病原菌的抗生素，對於因CAP而住院的成人之療效的Randomized trials。

資料收集與分析

由2位作者各自評估試驗品質、擷取資料，並計算Relative risks (RR)與95% confidence intervals (CI)，以Intentiontotreat (ITT) 的方式來評估治療成果。

主要結論

共有25個研究、5244位受試者被收錄。結果顯示，無論使用能或不能涵蓋非典型病原菌的抗生素，兩者的死亡率並沒有差別(RR 1.15，95% CI 0.85 �1.56)。能涵蓋非典型病原菌的抗生素似乎有稍好的治療成功率及殺菌效果，但這一現象在分析實驗設計品質較好的試驗時並沒有發現；涵蓋非典型病原菌的抗生素對於Legionella pneumophilae (L. pneumophilae) 有明顯較好的治療成效，但對於Pneumococcal pneumonia的治療成效稍差，不過差異並不顯著。兩種抗生素在副作用、或需要停用抗生素的發生率上均無差別，但使用涵蓋非典型病原菌抗生素的患者有較多腸胃道症狀(RR 0.73，95% CI 0.54 �0.99)。除了其中2篇研究以外，所有收錄的研究都在比較單一種涵蓋非典型病原菌的抗生素、與Betalactam類抗生素之間的效果差異，卻沒有任何研究比較兩者併用的效果。

作者結論

對於患有CAP的住院病人，經驗性投與可抗非典型病原菌的廣效型抗生素，對於存活率及臨床治療效果並沒有好處；此一結果主要來自於單用Quinolone類抗生素與Betalactam及Cephalosporins類抗生素的比較。我們未來需要更進一步的研究，來比較單用Betalactam或Cephalosporins類抗生素，及其與Macrolide類抗生素併用，在此一族群中造成的死亡率差異。

翻譯人

本摘要由慈濟醫院鄭育容翻譯。

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

總結

抗非典型病原菌之抗生素用於患有CAP的成年住院病人之效果引發肺炎的病原菌可區分為典型與非典型兩類，並需使用不同的抗生素來治療。非典型肺炎病原菌包括Legionella pneumophila (L. pneumophila)、Mycoplasma pneumoniae (M. pneumoniae)、Chlamydia pneumoniae (C. pneumoniae)等。在無法確認病原菌的疾病初期，通常會經驗地使用同時涵蓋典型與非典型病原菌的抗生素；因Streptococcus pneumoniae (S. pneumoniae) 是常見的致病菌，所以涵蓋典型肺炎病原菌是必要的，但目前尚未證實涵蓋非典型病原菌是否必要。這篇文章比較能與不能涵蓋非典型病原菌的抗生素，對於患有CAP的住院成人之治療成效；共有25個研究、5244位受試者被收錄，結果發現投與抗非典型病原菌的廣效型抗生素，對於存活率及臨床治療的效果並沒有好處。