Antistaphylococcal immunoglobulins to prevent staphylococcal infection in very low birth weight infants

  • Review
  • Intervention

Authors

  • Prakeshkumar S Shah,

    Corresponding author
    1. University of Toronto, Department of Paediatrics and Department of Health Policy, Management and Evaluation, Rm 775A, Toronto, Ontario, Canada
    • Prakeshkumar S Shah, Department of Paediatrics and Department of Health Policy, Management and Evaluation, Rm 775A, University of Toronto, 600 University Avenue, Toronto, Ontario, M5G 1XB, Canada. pshah@mtsinai.on.ca.

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  • David A Kaufman

    1. University of Virginia School of Medicine, Pediatrics, Charlottesville, Virginia, USA
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Abstract

Background

Nosocomial infection is a major problem affecting the immediate health and long-term outcome of preterm and very low birth weight neonates. More than half of these infections are caused by staphylococci. Various type specific antibodies targeted at different antigenic markers of Staphylococcus have been developed and have shown promise in animal studies.

Objectives

To evaluate the efficacy and safety of antistaphylococcal immunoglobulins in the prevention of Staphylococcal infection in very low birth weight infants.

Search methods

Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials (The Cochrane Library) were searched from their inception until February 2009. In addition, abstracts of major pediatric meetings of last seven years were searched.

Selection criteria

Randomized and quasi-randomized studies of antistaphylococcal immunoglobulins for the prevention of staphylococcal infections in preterm or very low birth weight neonates were reviewed by both authors for their eligibility for inclusion. Studies of any dose and/or route were included. Quality of studies was evaluated using criteria of masking of randomization, masking of intervention, completeness of follow-up and masking of outcome assessment by both review authors.

Data collection and analysis

Data from the primary author were obtained where published data provided inadequate information for the review or where relevant data could not be abstracted. Data were abstracted independently by both review authors. Statistical methods included calculation of relative risk (RR), risk difference (RD), number needed to treat (NNT) and weighted mean difference (WMD) when appropriate. Ninety five percent confidence intervals (CI) was used for these estimates of treatment effects. A fixed effect model was used for meta-analyses.

Main results

Three eligible studies were included (two studies of INH A-21 and one study of Altastaph involving a total of 2,701 neonates). Three reports of Pagibaximab were published as abstracts and will be considered for inclusion when further information is obtained. There were no significant differences noted in the risk of Staphylococcal infection between INH A-21 vs. placebo (typical RR 1.07, 95% CI 0.94, 1.22) or Altastaph vs. placebo (RR 0.86, 95% CI 0.32, 2.28); the risk of other bacterial infection between INH A-21 vs. placebo (typical RR 0.87, 95% CI 0.72, 1.06) or Altastaph vs. placebo (RR 0.93, 95% CI 0.53, 1.64); or the risk of any infection between INH A-21 vs. placebo (RR 1.00, 95% CI 0.91, 1.09) or Altastaph vs. placebo (RR 0.93, 95% CI 0.54, 1.62). There was no significant difference in the incidence of relevant secondary outcomes (chronic lung disease at 28 days, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage, retinopathy of prematurity or duration of antibiotic and vancomycin use).

Authors' conclusions

Antistaphylococcal immunoglobulins (INH A-21 and Altastaph) are not recommended for prevention of staphylococcal infections in preterm or VLBW neonates. Further research to investigate the efficacy of other products such as Pagibaximab is needed.

摘要

背景

抗葡萄球菌疫球蛋白預防極低出生體重嬰兒葡萄球菌感染

院內感染是影響早產兒與極低出生體重新生兒立即健康及長期預後的主要問題。超過一半的感染原是葡萄球菌。針對葡萄球菌不同抗原標記的不同型態的特殊抗體已被研發出來,並在動物實驗證明有效。

目標

評估抗萄球菌疫球蛋白預防極低出生體重嬰兒葡萄球菌感染的療效與安全性。

搜尋策略

搜尋2009年2月前Medline、Embase、CINAHL、 Cochrane Central Register of Controlled Trials (The Cochrane Library)。另外也搜尋最近7年主要小兒科會議摘要。

選擇標準

兩個作者回顧利用抗葡萄球菌免疫球蛋白預防極低體重新生兒葡萄球菌感染的隨機和半隨機對照試驗,以評估是否適合納入。任何給藥途徑皆納入。2位作者皆使用以下的標準評估研究的品質:隨機分配遮蔽(masking)、介入遮蔽、後續追蹤的完成度、以及結果評估遮蔽。

資料收集與分析

當研究所發表的數據不足以進行回顧或是無法摘錄重要數據的時候,則由主要作者處獲得相關數據,並且由2位作者獨立摘錄數據。如果合適的話,可採用統計方法計算相對風險(RR)、風險差異(RD)、益一需治數(NNT)及加權平均差(WMD)。利用95%信賴區間(CI)估計療效。並且利用固定效用模式(fixed effect model)進行統合分析。

主要結論

共3個符合資格的試驗被納入 (2個是INH A21的研究,而1個是Altastaph的研究,共包含2,701新生兒)。另有3個是關於Pagibaximab 的摘要,若未來可以取得相關資訊,則會考慮納入。研究中並未顯示對於葡萄球菌感染風險具有差異:INH A21與安慰劑(RR 1.07, 95% CI 0.94, 1.22);或Altastaph與安慰劑(RR 0.86, 95% CI 0.32, 2.28)。 而對於其他菌種來說也一樣沒有差異:INH A21與安慰劑(typical RR 0.87, 95% CI 0.72, 1.06);或Altastaph與安慰劑(RR 0.93, 95% CI 0.53, 1.64)。 而對於其他感染的風險也不具差異:INH A21與安慰劑(RR 1.00, 95% CI 0.91, 1.09)或Altastaph 與安慰劑(RR 0.93, 95% CI 0.54, 1.62)。 而次要結果(28天內發生慢性肺部疾病、 動脈導管未閉鎖、壞死性腸炎、腦室內出血、 早產兒視網膜病變或持續使用抗生素及使用萬古黴素)的發生率也沒有差異。

作者結論

不建議使用抗葡萄球菌免疫球蛋白 (INH A21與 Altastaph)預防新生兒或是極低體重嬰兒葡萄球菌感染。需要其他研究調查其他產品,譬如像是 Pagibaximab的療效。

翻譯人

本摘要由臺中榮民總醫院葉惠英翻譯。

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

總結

妊娠早期出生與極低出生體重的嬰兒具有高度敗血症風險。其原因部分是由於免疫系統尚未成熟,其中也包含免疫球蛋白過少。研究人員企圖以人工的方式,針對最常引起感染的細菌,提供抗體以提高免疫力。共3個研究於本處被回顧(其中2個是先導性試驗),不過並沒有顯示使用特定抗體對付常見細菌性感染的好處或風險。

Plain language summary

Antistaphylococcal immunoglobulins to prevent staphylococcal infection in very low birth weight infants

Babies born at earlier gestation and who are born with low birth weight are at significant risk of sepsis. This is in part due to the immaturity of the immune defence system, including low levels of immunoglobulins. Researchers attempted to boost the immune system by artificially providing antibodies specific to the most common bacteria causing such infections. Three studies reviewed here (two of which are pilot studies) revealed neither benefit nor risk associated with the preventative use of specific antibodies to common bacterial infections.