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Cochrane Database of Systematic Reviews

Antibiotic therapy for preventing infections in people with acute stroke

Information

DOI:
https://doi.org/10.1002/14651858.CD008530.pub3Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 22 January 2018see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:
  1. Cochrane Stroke Group

Copyright:
  1. Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors

  • Jan‐Dirk Vermeij

    Department of Neurology, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands

  • Willeke F Westendorp

    Department of Neurology, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands

  • Diederik WJ Dippel

    Erasmus MC University Medical Center, Rotterdam, Netherlands

  • Diederik van de Beek

    Department of Neurology, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands

  • Paul J Nederkoorn

    Correspondence to: Department of Neurology, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands

    [email protected]

Contributions of authors

J‐D Vermeij (JDV): performed the search, extracted data, and analysed and interpreted data.
WF Westendorp (WW): performed the search, extracted data, analysed and interpreted data, and drafted the review.
DWJ Dippel (DWJD): conceived and designed the review, assessed methodological quality, and provided final approval of the review for publication.
PJ Nederkoorn (PJN): performed analysis and interpretation of the data and commented on the review for its intellectual content.
D van de Beek (DVDB): commented on the review for intellectual content and provided final approval of the review for publication.

Sources of support

Internal sources

  • Academic Medical Center, Netherlands.

    Department of Neurology

  • Erasmus Medical Center, Netherlands.

    Department of Neurology

External sources

  • ZonMW, Netherlands.

    Grant: Netherlands Organisation for Health Research and Development (ZonMW): 171002302

  • Netherlands Heart Foundation, Netherlands.

    Grant: Netherlands Heart Foundation (Hartstichting): 2009B095

  • Netherlands Organization for Health Research and Development, Netherlands.

    Netherlands Organization for Health Research and Development (ZonMw; NWOVeni grant 2006 [916.76.023], NWO‐Vidi grant 2010 [016.116.358])

Declarations of interest

J‐D Vermeij (JDV): member of the study group of the Preventive Antibiotics in Stroke Study (ISRCTN66140176).
WF Westendorp (WW): member of the study group of the Preventive Antibiotics in Stroke Study (ISRCTN66140176).
DWJ Dippel (DWJD): member of the study group of the Preventive Antibiotics in Stroke Study (ISRCTN66140176).
PJ Nederkoorn (PJN): principal investigator of the Preventive Antibiotics in Stroke Study (ISRCTN66140176).
D van de Beek (DVDB): principal investigator of the Preventive Antibiotics in Stroke Study (ISRCTN66140176).

Acknowledgements

This work is supported by grants from the Netherlands Organization for Health Research and Development (ZonMW; 171002302) and the Netherlands Heart Foundation (Hartstichting; 2009B095). We especially thank Prof A Meisel for permitting us to use unpublished data from the STRAWINSKI trial in favour of this meta‐analysis. We also thank Dr A Chamorro, Dr M Boaz, and Dr Y Lampl, for providing additional data from their studies. Finally, we thank B van de Veen (BvdV) for assessing risk of bias of the manuscript by Westendorp et al.

Version history

Published

Title

Stage

Authors

Version

2018 Jan 22

Antibiotic therapy for preventing infections in people with acute stroke

Review

Jan‐Dirk Vermeij, Willeke F Westendorp, Diederik WJ Dippel, Diederik van de Beek, Paul J Nederkoorn

https://doi.org/10.1002/14651858.CD008530.pub3

2012 Jan 18

Antibiotic therapy for preventing infections in patients with acute stroke

Review

Willeke F Westendorp, Jan‐Dirk Vermeij, Frederique Vermeij, Heleen M Den Hertog, Diederik WJ Dippel, Diederik van de Beek, Paul J Nederkoorn

https://doi.org/10.1002/14651858.CD008530.pub2

2010 Jun 16

Antibiotic therapy for preventing infections in patients with acute stroke

Protocol

Frederique Vermeij, Paul J Nederkoorn, Heleen M Den Hertog, Diederik van de Beek, Diederik WJ Dippel

https://doi.org/10.1002/14651858.CD008530

Keywords

MeSH

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study, using the Cochrane 'Risk of bias' tool. '+' is defined as low risk of bias, '‐' as high risk of bias, '?' as unclear risk of bias.
Figures and Tables -
Figure 1

Risk of bias summary: review authors' judgements about each risk of bias item for each included study, using the Cochrane 'Risk of bias' tool. '+' is defined as low risk of bias, '‐' as high risk of bias, '?' as unclear risk of bias.

Study flow diagram.
Figures and Tables -
Figure 2

Study flow diagram.

Funnel plot of comparison: 1 Forest plot of comparison: primary outcomes, outcome: 1.1 Case fatality at the end of follow‐up.
Figures and Tables -
Figure 3

Funnel plot of comparison: 1 Forest plot of comparison: primary outcomes, outcome: 1.1 Case fatality at the end of follow‐up.

Funnel plot of comparison: 1 Forest plot of comparison: primary outcomes, outcome: 1.2 Death or dependency at the end of follow‐up.
Figures and Tables -
Figure 4

Funnel plot of comparison: 1 Forest plot of comparison: primary outcomes, outcome: 1.2 Death or dependency at the end of follow‐up.

Funnel plot of comparison: 2 Forest plot of comparison: secondary outcomes, outcome: 2.1 Number of infections at the end of follow‐up.
Figures and Tables -
Figure 5

Funnel plot of comparison: 2 Forest plot of comparison: secondary outcomes, outcome: 2.1 Number of infections at the end of follow‐up.

Funnel plot of comparison: 2 Forest plot of comparison: secondary outcomes, outcome: 2.2 Number of UTIs at the end of follow‐up.
Figures and Tables -
Figure 6

Funnel plot of comparison: 2 Forest plot of comparison: secondary outcomes, outcome: 2.2 Number of UTIs at the end of follow‐up.

Funnel plot of comparison: 2 Forest plot of comparison: secondary outcomes, outcome: 2.3 Number of pneumonias at the end of follow‐up.
Figures and Tables -
Figure 7

Funnel plot of comparison: 2 Forest plot of comparison: secondary outcomes, outcome: 2.3 Number of pneumonias at the end of follow‐up.

Comparison 1 Forest plot of comparison: primary outcomes, Outcome 1 Case fatality at the end of follow‐up.
Figures and Tables -
Analysis 1.1

Comparison 1 Forest plot of comparison: primary outcomes, Outcome 1 Case fatality at the end of follow‐up.

Comparison 1 Forest plot of comparison: primary outcomes, Outcome 2 Death or dependency at the end of follow‐up.
Figures and Tables -
Analysis 1.2

Comparison 1 Forest plot of comparison: primary outcomes, Outcome 2 Death or dependency at the end of follow‐up.

Comparison 2 Forest plot of comparison: secondary outcomes, Outcome 1 Number of infections at the end of follow‐up.
Figures and Tables -
Analysis 2.1

Comparison 2 Forest plot of comparison: secondary outcomes, Outcome 1 Number of infections at the end of follow‐up.

Comparison 2 Forest plot of comparison: secondary outcomes, Outcome 2 Number of UTIs at the end of follow‐up.
Figures and Tables -
Analysis 2.2

Comparison 2 Forest plot of comparison: secondary outcomes, Outcome 2 Number of UTIs at the end of follow‐up.

Comparison 2 Forest plot of comparison: secondary outcomes, Outcome 3 Number of pneumonias at the end of follow‐up.
Figures and Tables -
Analysis 2.3

Comparison 2 Forest plot of comparison: secondary outcomes, Outcome 3 Number of pneumonias at the end of follow‐up.

Comparison 3 Forest plot of comparison: sensitivity analyses, Outcome 1 Functional outcome: low risk of bias studies.
Figures and Tables -
Analysis 3.1

Comparison 3 Forest plot of comparison: sensitivity analyses, Outcome 1 Functional outcome: low risk of bias studies.

Comparison 3 Forest plot of comparison: sensitivity analyses, Outcome 2 Number of infections: low risk of bias studies.
Figures and Tables -
Analysis 3.2

Comparison 3 Forest plot of comparison: sensitivity analyses, Outcome 2 Number of infections: low risk of bias studies.

Comparison 3 Forest plot of comparison: sensitivity analyses, Outcome 3 Case fatality: double‐blind design.
Figures and Tables -
Analysis 3.3

Comparison 3 Forest plot of comparison: sensitivity analyses, Outcome 3 Case fatality: double‐blind design.

Comparison 3 Forest plot of comparison: sensitivity analyses, Outcome 4 Case fatality: open‐label design.
Figures and Tables -
Analysis 3.4

Comparison 3 Forest plot of comparison: sensitivity analyses, Outcome 4 Case fatality: open‐label design.

Comparison 3 Forest plot of comparison: sensitivity analyses, Outcome 5 Functional outcome: double‐blind design.
Figures and Tables -
Analysis 3.5

Comparison 3 Forest plot of comparison: sensitivity analyses, Outcome 5 Functional outcome: double‐blind design.

Comparison 3 Forest plot of comparison: sensitivity analyses, Outcome 6 Functional outcome: open‐label design.
Figures and Tables -
Analysis 3.6

Comparison 3 Forest plot of comparison: sensitivity analyses, Outcome 6 Functional outcome: open‐label design.

Preventive antibiotic therapy compared with placebo and/or conventional management in acute stroke

Patient or population: patients with acute ischaemic or haemorrhagic stroke

Setting: acute stroke management

Intervention: preventive antibiotic therapy for systemic use, at any dose or length of treatment

Comparison: placebo and/or conventional acute stroke management

Outcomes

Absolute risk

Relative effect
(95% CI)

No. of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with placebo and/or conventional management

Risk with preventive antibiotic treatment

Case fatality at the end of follow‐up

Study population

RR 1.03

(0.87 to 1.21)

4422

(8)

⊕⊕⊕⊕
higha,b

163 per 1000

169 per 1000

Poor functional outcome at the end of follow‐up

Study population

RR 0.99

(0.89 to 1.10)

4332

(7)

⊕⊕⊕⊕
moderatea,b.c.d.e

547 per 1000

535 per 1000

Number of infections at the end of follow‐up

Study population

RR 0.71

(0.58 to 0.88)

4317

(7)

⊕⊕⊕⊕
higha,b,f

259 per 1000

189 per 1000

Number of UTIs at the end of follow‐up

Study population

RR 0.40

(0.32 to 0.51)

4257

(6)

⊕⊕⊕⊕
higha,b

96 per 1000

39 per 1000

Number of pneumonias at the end of follow‐up

Study population

RR 0.95

(0.80 to 1.13)

4257

(6)

⊕⊕⊕⊕
higha,b

111 per 1000

105 per 1000

Occurrence of elevated body temperature

Insufficient data. Assessed qualitatively in only 2 studies

Rate of serious adverse events

No major side effects of preventive antibiotic therapy were reported.

*The absolute risk is calculated using the absolute numbers of events in both study arms.
CI: confidence interval; RR: risk ratio; UTIs: urinary tract infections.

GRADE Working Group grades of evidence.
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

aLarge number of included studies, large number of participants, and small confidence interval (ultimately low risk of bias). Good applicability in clinical practice.

bLimited publication bias cannot be excluded, as funnel plots for primary outcomes were skewed at the base, towards good outcomes.

cRegarding risk of bias of individual included studies, more than two of the included studies scored at least one criterion of ’unclear’ and/or ’high’ risk of bias on the Cochrane 'Risk of bias' summary (Figure 1). However, the effect on primary outcomes was consistent among studies with 'low' risk of bias.

dRegarding consistency of effect, heterogeneity was substantial (I² = 79%). However, overall effect estimates were precise. Stratifying for included studies with 'low risk of bias' resulted in loss of heterogeneity (I² = 4%) and did not affect outcomes. Therefore, we did not downgrade the quality of evidence.

eDowngraded owing to multiple remarks on GRADE considerations, despite the fact that all remarks can be explained and rectified.

fRegarding consistency of effect, heterogeneity was moderate (I² = 56%). However, overall effect estimates were precise. Therefore, we did not downgrade the quality of evidence.

Figures and Tables -
Comparison 1. Forest plot of comparison: primary outcomes

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Case fatality at the end of follow‐up Show forest plot

8

4422

Risk Ratio (M‐H, Random, 95% CI)

1.03 [0.87, 1.21]

2 Death or dependency at the end of follow‐up Show forest plot

7

4332

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.89, 1.10]

Figures and Tables -
Comparison 1. Forest plot of comparison: primary outcomes
Comparison 2. Forest plot of comparison: secondary outcomes

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of infections at the end of follow‐up Show forest plot

7

4317

Risk Ratio (M‐H, Random, 95% CI)

0.71 [0.58, 0.88]

2 Number of UTIs at the end of follow‐up Show forest plot

6

4257

Risk Ratio (M‐H, Random, 95% CI)

0.40 [0.32, 0.51]

3 Number of pneumonias at the end of follow‐up Show forest plot

6

4257

Risk Ratio (M‐H, Random, 95% CI)

0.95 [0.80, 1.13]

Figures and Tables -
Comparison 2. Forest plot of comparison: secondary outcomes
Comparison 3. Forest plot of comparison: sensitivity analyses

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Functional outcome: low risk of bias studies Show forest plot

6

4191

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.98, 1.06]

2 Number of infections: low risk of bias studies Show forest plot

6

4257

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.58, 0.89]

3 Case fatality: double‐blind design Show forest plot

2

215

Risk Ratio (M‐H, Fixed, 95% CI)

1.62 [0.87, 3.00]

4 Case fatality: open‐label design Show forest plot

5

4127

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.90, 1.17]

5 Functional outcome: double‐blind design Show forest plot

2

215

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.80, 1.27]

6 Functional outcome: open‐label design Show forest plot

5

4117

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.93, 1.03]

Figures and Tables -
Comparison 3. Forest plot of comparison: sensitivity analyses