Third generation cephalosporins versus conventional antibiotics for treating acute bacterial meningitis

 

Abstract

Background

Antibiotic therapy for suspected acute bacterial meningitis (ABM) needs to be started immediately, even before the results of cerebrospinal fluid (CSF) culture and antibiotic sensitivity are available. Immediate commencement of effective treatment using the intravenous route may reduce death and disability.

Objectives

The objective is to compare the effectiveness and safety of third generation cephalosporins (ceftriaxone or cefotaxime) with conventional treatment using penicillin or ampicillin-chloramphenicol in patients with community-acquired ABM.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (January 1966 to March week 4, 2011) and EMBASE (January 1974 to April 2011). We also searched the reference list of review articles and book chapters, and contacted experts for any unpublished trials.

Selection criteria

Randomised controlled trials (RCTs) comparing third generation cephalosporins (ceftriaxone or cefotaxime) with conventional antibiotics (ampicillin-chloramphenicol combination, or chloramphenicol alone) as empirical therapy for ABM in adults and children.

Data collection and analysis

Two review authors independently applied the study selection criteria, assessed methodological quality and extracted data.

Main results

Nineteen trials that involved 1496 patients were included in the analysis. There was no heterogeneity of results among the studies in any outcome except diarrhoea. There was no statistically significant difference between the groups in the risk of death (risk difference (RD) 0%; 95% confidence interval (CI) -3% to 2%), risk of deafness (RD -4%; 95% CI -9% to 1%) or risk of treatment failure (RD -1%; 95% CI -4% to 2%). However, there were significantly decreased risks of culture positivity of CSF after 10 to 48 hours (RD -6%; 95% CI -11% to 0%) and statistically significant increases in the risk of diarrhoea between the groups (RD 8%; 95% CI 3% to 13%) with the third generation cephalosporins. The risk of neutropaenia and skin rash were not significantly different between the two groups. However, due to increased antibiotic resistance since the 1980s, the finding of this review should be read with caution.

Authors' conclusions

The review shows no clinically important difference between third generation cephalosporins (ceftriaxone or cefotaxime) and conventional antibiotics (ampicillin-chloramphenicol combination, or chloramphenicol alone). Therefore the choice of antibiotic will depend on cost and availability. The antimicrobial resistance pattern against various antibiotics needs to be closely monitored in low- to middle-income countries as well as high-income countries.

 

Plain language summary

Newer, third generation cephalosporins versus conventional antibiotics for treating acute bacterial meningitis

Acute bacterial meningitis is a life-threatening illness. Currently the evidence suggests that old and new antibiotics offer the same level of treatment. Bacteria which cause meningitis are often thought to be resistant to conventional (older) antibiotics, and so doctors often prescribe newer antibiotics (called third generation cephalosporins). Commencing treatment early is vitally important and the choice of antibiotic is often made without any knowledge of possible drug resistance. This review examined 19 studies with 1496 participants to see whether there is a difference in effectiveness between conventional and newer antibiotics. This review found no differences. Adverse effects in both approaches were similar, except for diarrhoea, which was more common in the cephalosporin group. Only three studies dealt with adults; the remaining studies recruited participants aged 15 years and younger. Therefore, we believe that the results probably pertain more to children. Conventional and newer antibiotics seem reasonable options for initial, immediate treatment. The choice may depend on availability, affordability and local policies.

 

摘要

背景

在治療急性細菌性腦膜炎上，比較第三代頭芽孢菌素及傳統抗生素的治療成果

針對疑似急性細菌性腦膜炎的病人，在腦脊髓液培養結果尚未得知、細菌敏感性尚未確認前，就應立即開始抗生素治療。即時靜脈注射有效的抗生素可以減少死亡率及併發症。雖然細菌性腦膜炎治療指引建議我們使用第三代頭芽孢菌素，在經濟較落後的國家卻經常無法取得此類藥物。

目標

此回顧分析的目標，是比較在社區感染的急性細菌性腦膜炎病人，使用第三代頭芽孢菌素及傳統抗生素(盤尼西林及或Ampicillinchloramphenicol)之治療成果與安全性。

搜尋策略

我們搜尋了 the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1)，包括Cochrane Acute Respiratory Infections Group Trials Register、MEDLINE (January 1966 至 March 2007)、及 EMBASE (January 1974 至 March 2007)；我們也搜尋回顧文章及相關書籍章節中的參考資料，同時跟專家討論尚未發表的試驗。

選擇標準

隨機對照試驗(RCTs) 比較以ceftriaxone 或cefotaxime，搭配傳統抗生素作為 急性細菌性腦膜炎經驗療法。

資料收集與分析

兩位作者各自獨立完成試驗的篩選、資料的收集及評估方法學上的品質。

主要結論

我們囊括了19個試驗，共1496位病患進入這個回顧分析。在結果分析中，除了腹瀉外，兩組沒有太多歧異；在死亡、失明、治療失敗的風險比較上，兩組沒有顯著差別。死亡的風險差異度是0%，95%信賴區間為 −3%2%；失明的風險差異度是 −4%，95%信賴區間為 −9%1%，治療失敗的風險差異度是 −1%，95%信賴區間為 −4%2%)。 在投予第三代頭芽孢菌素這組，在10 – 48小時後腦脊髓液培養陽性的機率明顯降低(風險差異度 −6%，95%信賴區間為 −11%0%)，腹瀉機率明顯提高(風險差異度8%，95%信賴區間為3%13%)。至於發生白血球低下及皮膚發疹的比例，兩組沒有顯著差異。 然而，所有的試驗只有三個不是在1980年代開始進行的，分別發表在1993年、1996年及2005年。

作者結論

這個回顧分析顯示使用第三代頭芽孢菌素(Ceftriaxone或cefotaxime)或傳統抗生素臨床上沒有顯著的差異。因此，在需要考量藥物供應、經濟狀況的情形下，第三代頭芽孢菌素、ampicillin加chloramphenicol、單用chloramphenicol都是可以考慮的選擇。至於不同細菌對抗生素的抗藥性，高收入國家應該要跟低中收入國家一樣嚴格的監控。

翻譯人

本摘要由臺灣大學附設醫院簡郁珊翻譯。

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

總結

急性細菌性腦膜炎是一個會威脅生命的疾病。現今的證據顯示舊的跟新的抗生素有相同的療效；然腦膜炎的致病菌較常對傳統抗生素具有抗藥性，故儘管在經濟較落後但疾病盛行的國家，可能無法取得或負擔，醫生仍經常處方較新的第三代頭芽孢菌素。儘早投予抗生素是很重要的，投藥時經常無法得知細菌的抗藥性；此回顧分析發現在藥物的效果上，較新的藥物與傳統的藥物沒有太大的差異，故兩者似乎都是開始治療時的合理選擇。