Erythromycin for the prevention of chronic lung disease in intubated preterm infants at risk for, or colonized or infected with Ureaplasma urealyticum

  • Review
  • Intervention

Authors


Abstract

Background

Controversy exists over whether or not Ureaplasma urealyticum colonization or infection of the respiratory tract contributes to the severity of chronic lung disease (CLD), a major cause of morbidity and mortality in preterm infants.

Objectives

To evaluate the efficacy and safety of prophylactic or therapeutic erythromycin in preventing chronic lung disease in intubated preterm infants with unknown U. urealyticum status or proven positivity.

Search methods

Searches were done of MEDLINE (1966-June 9, 2003), EMBASE (1980-May 5, 2003), The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2002), previous reviews including cross-references, and abstracts of conference proceedings (Pediatric Academic Societies 2000-2003, American Thoracic Society 2001-2003). There were no language restrictions. Expert informants were contacted.

Selection criteria

Randomized or quasi-randomized studies comparing either prophylactic or therapeutic administration of oral or intravenous erythromycin (regardless of dose and duration) versus no treatment or placebo among intubated preterm infants <37 weeks and <2500 grams with either unknown U. urealyticum status or proven positivity by culture or polymerase chain reaction.

Data collection and analysis

Data were extracted by all of the authors independently and differences were resolved by consensus. Treatment effects for categorical outcomes were expressed as relative risk, with 95% confidence intervals.

Main results

Two small controlled studies, both involving intubated babies <30 weeks gestation, were eligible for inclusion. Lyon 1998 tested prophylactic erythromycin in babies whose U. urealyticum status was unknown at the time of initiation of treatment. Jonsson 1998 tested erythromycin in babies known to be culture positive for U. urealyticum. Neither trial showed a statistically significant effect of erythromycin on CLD, death or the combined outcome CLD or death. Because the two studies differed importantly in their design, the results were not combined in meta-analyses. No adverse effects of a 7-10 day course of erythromycin were reported in either study.

Authors' conclusions

Current evidence does not demonstrate a reduction in CLD/death when intubated preterm infants are treated with erythromycin prophylactically before U. urealyticum culture/PCR results are known or when Ureaplasma colonized, intubated preterm infants are treated with erythromycin. However, a true benefit could easily have been missed with the small sample sizes in the two eligible studies. The studies were greatly underpowered to detect uncommon adverse effects such as pyloric stenosis. Additional controlled trials are required to determine whether antibiotic therapy of Ureaplasma reduces CLD and/or death in intubated preterm infants.

摘要

背景

對於插管並有感染風險,體內群聚或已感染溶尿尿漿菌(Ureaplasma urealyticum)之早產兒使用紅黴素治療來預防慢性肺疾病.

慢性肺疾病是早產兒罹病及死亡的一個主要原因, 對於在呼吸道群聚或感染溶尿尿漿菌(Ureaplasma urealyticum)是否影響慢性肺疾病的嚴重程度仍存有爭議.

目標

評估在未知或已證實有溶尿尿漿菌(Ureaplasma urealyticum)感染之插管早產兒使用預防性之紅黴素治療對於預防慢性肺疾病之成效及安全性.

搜尋策略

1. 搜尋範圍包括MEDLINE (1966June 9,2003), EMBASE (1980May 5, 2003), The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2002), 先前交叉引用的回顧文章,以及會議紀錄摘要(Pediatric Academic Societies 2000 – 2003, American Thoracic Society 2001 – 2003). 2. 語言方面沒有限制. 3. 專家意見亦被列入.

選擇標準

1. 隨機或似隨機的研究. 2. 對象: 未知感染或用培養或聚合酵素鏈鎖反應(PCR)已證實有溶尿尿漿菌(Ureaplasma urealyticum)感染之插管早產兒(懷孕周數小於37周,出生體重小於2500公克). 3. 研究內容: 比較使用預防性或治療性紅黴素的早產兒(劑量,治療期間,口服或靜脈注射:皆無限制)相對於沒有紅黴素或使用安慰劑治療的早產兒.

資料收集與分析

資料由所有作者獨立摘錄,差異處由共同共識解決. 各個預後種類的治療效果以相對危險值的95%的信賴區間呈現.

主要結論

1. 共有兩篇研究符合選擇標準,對象都包括懷孕周數小於30周並插管的早產兒. 2. 在1998年, Lyon 學者針對未證實溶尿尿漿菌(Ureaplasma urealyticum)感染之早產兒給予預防性紅黴素治療. 3. 在1998年, Jonsson 在溶尿尿漿菌(Ureaplasma urealyticum)培養陽性的早產兒使用紅黴素治療. 4. 兩篇文章都無法證實以紅黴素治療對於慢性肺疾病,死亡及兩者結合的預後有統計學上的意義. 5. 因這兩篇研究在設計上有很大的差異,研究結果不能做交叉分析. 6. 兩篇研究的七到十天的紅黴素治療療程中,沒有併發症被報導.

作者結論

1. 對於未用培養或聚合酵素鏈鎖反應(PCR)證實有溶尿尿漿菌(Ureaplasma urealyticum)感染之插管早產兒使用預防性紅黴素治療及溶尿尿漿菌(Ureaplasma urealyticum)群聚之插管早產兒使用紅黴素治療, 現今的證據無法證實能降低慢性肺疾病及死亡. 2. 因為兩個研究的個案數目少, 真正的益處可能很容易因此而被忽略. 這些研究對於檢驗常見的不良反應(如:幽門狹窄)的檢力相當低;因此需要其他的對照試驗,以確定抗生素治療尿漿菌是否可以降低插管嬰兒CLD以及/或死亡的情況。

翻譯人

本摘要由臺中榮民總醫院許登欽翻譯。

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

總結

還需要更多使用抗生素於溶尿尿漿菌陽性的嬰兒預防慢性肺病的證據。慢性肺病(CLD)通常對於使用呼吸器(機械輔助呼吸)的嬰兒來說是個重大的健康風險。溶尿尿漿菌是常見的一種感染,儘管還沒有被證實,不過它可能造成CLD。Erythromycin是一種用來治療另一種溶尿尿漿菌感染的抗生素,當嬰兒檢驗出來為溶尿尿漿菌陽性時,嘗試使用erythromycin預防感染。本文獻回顧發現沒有足夠的證據顯示是否新生兒需要檢驗溶尿尿漿菌,以及是否使用erythromycin可以預防CLD或死亡。

Plain language summary

Erythromycin for the prevention of chronic lung disease in intubated preterm infants at risk for, or colonized or infected with Ureaplasma urealyticum

More evidence needed on using antibiotics to try and prevent chronic lung disease in preterm babies testing positive for U urealyticum. Chronic lung disease (CLD) is a major health risk often faced by preterm babies on ventilation (machine-assisted breathing). Ureaplasma urealyticum is a common type of infection that may be one of the causes of CLD, although this has not been proven. Erythromycin is an antibiotic used for other infections caused by U urealyticum. When a baby tests positive for U urealyticum, erythromycin has been tried as a preventive measure. The review found that there is not enough evidence from trials to show whether or not testing preterm babies for U urealyticum and using erythromycin can prevent CLD or mortality.

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