Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease

 

Abstract

Background

People with sickle cell disease are particularly susceptible to infection. Infants and very young children are especially vulnerable, and the 'Co-operative Study of Sickle Cell Disease' observed an incidence rate of 10 per 100 patient years of pneumococcal septicaemia in children under the age of three. Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimens may be advisable for this population.

Objectives

To assess the effects of prophylactic antibiotic regimens for preventing pneumococcal infection in children with sickle cell disease.

Search methods

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which is comprised of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.

Date of the most recent search: 09 April 2010.

Selection criteria

All randomised or quasi-randomised controlled trials comparing prophylactic antibiotics to prevent pneumococcal infection in children with sickle cell disease with placebo, no treatment or a comparator drug.

Data collection and analysis

Both authors independently extracted data and assessed trial quality.

Main results

Five trials were identified by the initial search, of which three trials met the inclusion criteria. All of the included trials showed a reduced incidence of infection in children with sickle cell disease (SS or Sβ0Thal) receiving prophylactic penicillin. In trials which investigated initiation of penicillin on risk of pneumococcal infection, the odds ratio was 0.37 (95% CI 0.16 to 0.86), while for withdrawal the odds ratio was 0.49 (95% CI 0.09 to 2.71). Adverse drug effects were rare and minor. Rates of pneumococcal infection were found to be relatively low in children over the age of five.

Authors' conclusions

Prophylactic penicillin significantly reduces risk of pneumococcal infection in children with homozygous sickle cell disease, and is associated with minimal adverse reactions. Further research may help to determine the ideal age to safely withdraw penicillin.

 

Plain language summary

Regular antibiotics for preventing pneumococcal infection in young children with sickle cell disease

People with sickle cell disease (SCD) are especially prone to respiratory infections and blood poisoning. These infections are often caused by pneumococcal bacteria. Infections occur partly due to the spleen not working correctly, but also because damaged tissue and bone resulting from SCD can harbour bacteria. The highest risk of infection occurs in children under three years old, but the usual pneumococcal vaccines are of limited use in these patients. Therefore regular antibiotics are needed to prevent infection. As risk of infection decreases with age, there might be a time when preventative antibiotic treatment can be halted. Three trials with over 800 children are included in the review. All three trials showed a reduced rate of infection in children with sickle cell disease receiving penicillin preventatively. Two trials looked at whether treatment was effective. The third trial followed on from one of the early trials and looked at when it was safe to stop treatment. Adverse drug effects were rare and minor. However, there were problems with children keeping to the treatment schedule and with the development of antibiotic resistance. We conclude that penicillin given preventatively reduces the rate of pneumococcal infections in children with sickle cell disease under five years old. The risk of infection in older children is lower, and the follow-on trial did not show a significant increase in risk when regular penicillin was halted at five years old. Further research should look at how common and how clinically important resistant bacteria are.

 

摘要

背景

避免鐮刀型貧血孩童肺炎鏈球菌感染的預防性抗生素使用

鐮刀型貧血病人很容易受各種感染，尤其是嬰兒以及年紀很小的孩童更是容易感染。而“Cooperative Study of Sickle Cell Disease”觀察到每100個病人年就有10件3歲以下孩童肺炎鏈球菌敗血症感染。對於這個年齡群，即使是平常所施行的疫苗注射，功效都十分有限。所以，對於這個年齡群採取盤林西林(penicillin) 預防性注射不失為一個明智的選擇。

目標

評估預防鐮刀型貧血的孩童肺炎鏈球菌感染，預防性抗生素的使用是否有效。

搜尋策略

我們搜尋了Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register，其中包含了廣泛的電子資料庫的搜尋並以人工搜尋相關期刊研討會摘要手冊。最新的搜尋日期:2007年6月。

選擇標準

我們收納比較預防鐮刀型貧血的孩童肺炎鏈球菌感染，預防性抗生素的使用比安慰劑，或是比較沒有治療或是其他對比性的藥物，皆為隨機或半隨機對照試驗。

資料收集與分析

兩位作者皆獨立擷取數據並評估試驗的品質。

主要結論

5個試驗符合最初搜尋條件，但只有3個試驗符合選擇標準。所有符合選擇標準的試驗結果皆表示接受預防性盤林西林注射的鐮刀性貧血孩童能減少感染的發生。Odds ratio:0.37 (95% CI 0.16 至 0.86), while for withdrawal the odds ratio was 0.49 (95% CI 0.09 to 2.71).藥物不良反應很少見且不嚴重。而5歲以上的孩童肺炎鏈球菌感染機率是相對的低。

作者結論

盤林西林預防性的注射可以減少鐮刀型貧血孩童肺炎鏈球菌感染，並且藥物不良反應很小。未來的研究方向應探討甚麼是停止盤林西林預防性注射最適當的年紀。

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

鐮刀型貧血病人特別容易遭受呼吸道感染與血液感染，而大部分的感染都是肺炎鏈球菌。容易遭受感染在某種程度上是因為脾臟無法發揮正常的免疫功能，而鐮刀型貧血所造成組織跟骨頭的損壞變成細菌感染的溫床，其中又以三歲以下的孩童最易遭受感染，而肺炎鏈球菌的疫苗往往只有限的功效，所以預防性抗生素的使用是需要的。但是隨著年齡增長，感染機率的降低，何時該停止使用預防性抗生素呢?此篇回顧包含3個試驗，囊括了800個孩童。這3個臨床試驗抗生素預防性注射皆降低了鐮刀性貧血兒童的感染率，其中兩個臨床試驗探討何者為有效的治療，其中一個探討了何時為停止治療的適當時機。藥物不良反應很少見，但是兒童的用藥服從性跟抗藥性會是將來的課題。總結而言，盤林西林預防性注射有效降低五歲以下的病童肺炎鏈球菌感染，五歲以上感染率本身就低，而五歲過後停止預防性注射並不會增加感染率，未來的研究方向應該著重探討抗藥性細菌的普及程度與臨床重要程度。