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Meta-Analysis
. 2018 Jan 22;1(1):CD008530.
doi: 10.1002/14651858.CD008530.pub3.

Antibiotic therapy for preventing infections in people with acute stroke

Jan-Dirk Vermeij  1 , Willeke F Westendorp, Diederik Wj Dippel, Diederik van de Beek, Paul J Nederkoorn
Affiliations
Meta-Analysis

Antibiotic therapy for preventing infections in people with acute stroke

Jan-Dirk Vermeij et al. Cochrane Database Syst Rev. .

Abstract

Background: Stroke is the main cause of disability in high-income countries and ranks second as a cause of death worldwide. Infections occur frequently after stroke and may adversely affect outcome. Preventive antibiotic therapy in the acute phase of stroke may reduce the incidence of infections and improve outcome. In the previous version of this Cochrane Review, published in 2012, we found that antibiotics did reduce the risk of infection but did not reduce the number of dependent or deceased patients. However, included studies were small and heterogeneous. In 2015, two large clinical trials were published, warranting an update of this Review.

Objectives: To assess the effectiveness and safety of preventive antibiotic therapy in people with ischaemic or haemorrhagic stroke. We wished to determine whether preventive antibiotic therapy in people with acute stroke:• reduces the risk of a poor functional outcome (dependency and/or death) at follow-up;• reduces the occurrence of infections in the acute phase of stroke;• reduces the occurrence of elevated body temperature (temperature ≥ 38° C) in the acute phase of stroke;• reduces length of hospital stay; or• leads to an increased rate of serious adverse events, such as anaphylactic shock, skin rash, or colonisation with antibiotic-resistant micro-organisms.

Search methods: We searched the Cochrane Stroke Group Trials Register (25 June 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5; 25 June 2017) in the Cochrane Library; MEDLINE Ovid (1950 to 11 May 2017), and Embase Ovid (1980 to 11 May 2017). In an effort to identify further published, unpublished, and ongoing trials, we searched trials and research registers, scanned reference lists, and contacted trial authors, colleagues, and researchers in the field.

Selection criteria: Randomised controlled trials (RCTs) of preventive antibiotic therapy versus control (placebo or open control) in people with acute ischaemic or haemorrhagic stroke.

Data collection and analysis: Two review authors independently selected articles and extracted data; we discussed and resolved discrepancies at a consensus meeting with a third review author. We contacted study authors to obtain missing data when required. An independent review author assessed risk of bias using the Cochrane 'Risk of bias' tool. We calculated risk ratios (RRs) for dichotomous outcomes, assessed heterogeneity amongst included studies, and performed subgroup analyses on study quality.

Main results: We included eight studies involving 4488 participants. Regarding quality of evidence, trials showed differences in study population, study design, type of antibiotic, and definition of infection; however, primary outcomes among the included studies were consistent. Mortality rate in the preventive antibiotic group was not significantly different from that in the control group (373/2208 (17%) vs 360/2214 (16%); RR 1.03, 95% confidence interval (CI) 0.87 to 1.21; high-quality evidence). The number of participants with a poor functional outcome (death or dependency) in the preventive antibiotic therapy group was also not significantly different from that in the control group (1158/2168 (53%) vs 1182/2164 (55%); RR 0.99, 95% CI 0.89 to 1.10; moderate-quality evidence). However, preventive antibiotic therapy did significantly reduce the incidence of 'overall' infections in participants with acute stroke from 26% to 19% (408/2161 (19%) vs 558/2156 (26%); RR 0.71, 95% CI 0.58 to 0.88; high-quality evidence). This finding was highly significant for urinary tract infections (81/2131 (4%) vs 204/2126 (10%); RR 0.40, 95% CI 0.32 to 0.51; high-quality evidence), whereas no preventive effect for pneumonia was found (222/2131 (10%) vs 235/2126 (11%); RR 0.95, 95% CI 0.80 to 1.13; high-quality evidence). No major side effects of preventive antibiotic therapy were reported. Only two studies qualitatively assessed the occurrence of elevated body temperature; therefore, these results could not be pooled. Only one study reported length of hospital stay.

Authors' conclusions: Preventive antibiotics had no effect on functional outcome or mortality, but significantly reduced the risk of 'overall' infections. This reduction was driven mainly by prevention of urinary tract infection; no effect for pneumonia was found.

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Conflict of interest statement

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).

Figures

1
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.
2
2
Study flow diagram.
3
3
Funnel plot of comparison: 1 Forest plot of comparison: primary outcomes, outcome: 1.1 Case fatality at the end of follow‐up.
4
4
Funnel plot of comparison: 1 Forest plot of comparison: primary outcomes, outcome: 1.2 Death or dependency at the end of follow‐up.
5
5
Funnel plot of comparison: 2 Forest plot of comparison: secondary outcomes, outcome: 2.1 Number of infections at the end of follow‐up.
6
6
Funnel plot of comparison: 2 Forest plot of comparison: secondary outcomes, outcome: 2.2 Number of UTIs at the end of follow‐up.
7
7
Funnel plot of comparison: 2 Forest plot of comparison: secondary outcomes, outcome: 2.3 Number of pneumonias at the end of follow‐up.
1.1
1.1. Analysis
Comparison 1 Forest plot of comparison: primary outcomes, Outcome 1 Case fatality at the end of follow‐up.
1.2
1.2. Analysis
Comparison 1 Forest plot of comparison: primary outcomes, Outcome 2 Death or dependency at the end of follow‐up.
2.1
2.1. Analysis
Comparison 2 Forest plot of comparison: secondary outcomes, Outcome 1 Number of infections at the end of follow‐up.
2.2
2.2. Analysis
Comparison 2 Forest plot of comparison: secondary outcomes, Outcome 2 Number of UTIs at the end of follow‐up.
2.3
2.3. Analysis
Comparison 2 Forest plot of comparison: secondary outcomes, Outcome 3 Number of pneumonias at the end of follow‐up.
3.1
3.1. Analysis
Comparison 3 Forest plot of comparison: sensitivity analyses, Outcome 1 Functional outcome: low risk of bias studies.
3.2
3.2. Analysis
Comparison 3 Forest plot of comparison: sensitivity analyses, Outcome 2 Number of infections: low risk of bias studies.
3.3
3.3. Analysis
Comparison 3 Forest plot of comparison: sensitivity analyses, Outcome 3 Case fatality: double‐blind design.
3.4
3.4. Analysis
Comparison 3 Forest plot of comparison: sensitivity analyses, Outcome 4 Case fatality: open‐label design.
3.5
3.5. Analysis
Comparison 3 Forest plot of comparison: sensitivity analyses, Outcome 5 Functional outcome: double‐blind design.
3.6
3.6. Analysis
Comparison 3 Forest plot of comparison: sensitivity analyses, Outcome 6 Functional outcome: open‐label design.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Chamorro 2005 {published data only}
    1. Chamorro A, Horcajada JP, Obach V, Vargas M, Revilla M, Torres F, et al. The Early Systemic Prophylaxis of Infection After Stroke study: a randomized clinical trial. Stroke 2005;36(7):1495‐500. - PubMed
De Falco 1998 {published data only}
    1. Falco FA, Santangelo R, Majello L, Angelone P. Antimicrobial prophylaxis in the management of ischemic stroke. Rivista di Neurobiologia 1998;44(1):63‐7.
Harms 2008 {published data only}
    1. Harms H, Prass K, Meisel C, Klehmet J, Rogge W, Drenckhahn C, et al. Preventive antibacterial therapy in acute ischemic stroke: a randomized controlled trial. PLoS ONE 2008;3(5):e2158. - PMC - PubMed
Kalra 2015 {published data only}
    1. Kalra L, Irshad S, Hodsoll J, Simpson M, Gulliford M, Smithard D, STROKE‐INF Investigators. Prophylactic antibiotics after acute stroke for reducing pneumonia in patients with dysphagia (STROKE‐INF): a prospective, cluster‐randomised, open‐label, masked endpoint, controlled clinical trial. Lancet 2015;386(10006):1835‐44. - PubMed
Lampl 2007 {published data only}
    1. Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A, et al. Minocycline treatment in acute stroke: an open‐label, evaluator‐blinded study. Neurology 2007;69(14):1404‐10. - PubMed
Schwarz 2008 {published data only}
    1. Schwarz S, Al‐Shajlawi F, Sick C, Meairs S, Hennerici MG. Effects of prophylactic antibiotic therapy with mezlocillin plus sulbactam on the incidence and height of fever after severe acute ischemic stroke: the Mannheim Infection in Stroke Study (MISS). Stroke 2008;39(4):1220‐7. - PubMed
Ulm 2016 {unpublished data only}
    1. Meisel A. The randomised controlled STRAWINSKI trial: procalcitonin‐guided antibiotic therapy after stroke (preliminary title). Unpublished. - PMC - PubMed
Westendorp 2015 {published data only}
    1. Westendorp WF, Vermeij JD, Zock E, Hooijenga IJ, Kruyt ND, Bosboom HJ, PASS Investigators. The Preventive Antibiotics in Stroke Study (PASS): a pragmatic randomised open‐label masked endpoint clinical trial. Lancet 2015;385(9977):1519‐26. - PubMed

References to ongoing studies

ISRCTN82217627 {unpublished data only}
    1. ISRCTN82217627. Prevention of complications to Improve outcome in elderly patients with acute stroke ‐ a randomised clinical trial. www.isrctn.com/ISRCTN82217627 (first received 29 August 2015).

Additional references

Carnaby 2006
    1. Carnaby G, Hankey GJ, Pizzi J. Behavioural intervention for dysphagia in acute stroke: a randomised controlled trial. Lancet Neurology 2006;5(1):31‐7. - PubMed
Chamorro 2006
    1. Chamorro A, Amaro S, Vargas M, Obach V, Cervera A, Torres F, et al. Interleukin 10, monocytes and increased risk of early infection in ischaemic stroke. Journal of Neurology, Neurosurgery and Psychiatry 2006;77(11):1279‐81. - PMC - PubMed
Emsley 2008
    1. Emsley HC, Hopkins SJ. Acute ischaemic stroke and infection: recent and emerging concepts. Lancet Neurology 2008;7(4):341‐53. - PubMed
Finlayson 2011
    1. Finlayson O, Kapral M, Hall R, Asllani E, Selchen D, Saposnik G, Canadian Stroke Network, Stroke Outcome Research Canada (SORCan) Working Group. Risk factors, inpatient care, and outcomes of pneumonia after ischemic stroke. Neurology 2011;77:1338–45. - PubMed
Haeusler 2008
    1. Haeusler KG, Schmidt WU, Fohring F, Meisel C, Helms T, Jungehulsing GJ, et al. Cellular immunodepression preceding infectious complications after acute ischemic stroke in humans. Cerebrovascular Diseases 2008;25(1‐2):50‐8. - PubMed
Hamidon 2003
    1. Hamidon BB, Raymond AA. Risk factors and complications of acute ischaemic stroke patients at Hospital Universiti Kebangsaan Malaysia (HUKM). Medical Journal of Malaysia 2003;58(4):499‐505. - PubMed
Higgins 2016
    1. Higgins JPT, Lasserson T, Chandler J, Tovey D, Churchill R. Methodological Expectations of Cochrane Intervention Reviews. London: Cochrane, 2016.
Jauch 2013
    1. Jauch EC, Saver JL, Adams HP, Bruno A, Connors JJ, Demaerschalk BM, American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Peripheral Vascular Disease, and Council on Clinical Cardiology. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44:870‐947. - PubMed
Kammersgaard 2001
    1. Kammersgaard LP, Jorgensen HS, Reith J, Nakayama H, Houth JG, Weber UJ, et al. Early infection and prognosis after acute stroke: the Copenhagen Stroke Study. Journal of Stroke and Cerebrovascular Diseases 2001;10(5):217‐21. - PubMed
Kishore 2015
    1. Kishore AK, Vail A, Chamorro A, Garau J, Hopkins SJ, Napoli M, et al. How is pneumonia diagnosed in clinical stroke research? A systematic review and meta‐analysis. Stroke 2015;46:1202‐9. - PubMed
Kwon 2006
    1. Kwon HM, Jeong SW, Lee SH, Yoon BW. The pneumonia score: a simple grading scale for prediction of pneumonia after acute stroke. American Journal of Infection Control 2006;34(2):64‐8. - PubMed
Lee 2007
    1. Lee M, Huang WY, Weng HH, Lee JD, Lee TH. First‐ever ischemic stroke in very old Asians: clinical features, stroke subtypes, risk factors and outcome. European Neurology 2007;58(1):44‐8. - PubMed
Martino 2005
    1. Martino R, Foley N, Bhogal S, Diamant N, Speechley M, Teasell R. Dysphagia after stroke: incidence, diagnosis, and pulmonary complications. Stroke 2005;36(12):2756‐63. - PubMed
Popović 2013
    1. Popović N, Stefanović‐Budimkić M, Mitrović N, Urošević A, Milošević B, Pelemiš M, et al. The frequency of poststroke infections and their impact on early stroke outcome. Journal of Stroke and Cerebrovascular Diseases 2013;22:424–9. - PubMed
RevMan 2014 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Smith 2015
    1. Smith CJ, Kishore AK, Vail A, Chamorro A, Garau J, Hopkins SJ, et al. Diagnosis of stroke‐associated pneumonia: recommendations from the Pneumonia in Stroke Consensus Group. Stroke 2015;46(8):2335‐40. - PubMed
Smyth 2011
    1. Smyth RM, Kirkham JJ, Jacoby A, Altman DG, Gamble C, Williamson PR. Frequency and reasons for outcome reporting bias in clinical trials: interviews with trialists. BMJ 2011;342:c7153. - PMC - PubMed
Stott 2009
    1. Stott DJ, Falconer A, Miller H, Tilston JC, Langhorne P. Urinary tract infection after stroke. QJM 2009;102(4):243‐9. - PubMed
Van de Beek 2009
    1. Beek D, Wijdicks EF, Vermeij FH, Haan RJ, Prins JM, Spanjaard L, et al. Preventive antibiotics for infections in acute stroke: a systematic review and meta‐analysis. Archives of Neurology 2009;66(9):1076‐81. - PubMed
Van der Worp 2007
    1. Worp HB, Gijn J. Clinical practice. Acute ischemic stroke. New England Journal of Medicine 2007;357(6):572‐9. - PubMed
Vargas 2006
    1. Vargas M, Horcajada JP, Obach V, Revilla M, Cervera A, Torres F, et al. Clinical consequences of infection in patients with acute stroke: is it prime time for further antibiotic trials?. Stroke 2006;37(2):461‐5. - PubMed
Vermeij 2009
    1. Vermeij FH, Scholte op Reimer WJ, Man P, Oostenbrugge RJ, Franke CL, Jong G, et al. Stroke‐associated infection is an independent risk factor for poor outcome after acute ischemic stroke: data from the Netherlands Stroke Survey. Cerebrovascular Diseases 2009;27(5):465‐71. - PubMed
Vermeij 2016
    1. Vermeij JD, Westendorp WF, Roos YB, Brouwer MC, Beek D, Nederkoorn PJ, PASS Investigators. Preventive ceftriaxone in patients with stroke treated with intravenous thrombolysis: post hoc analysis of the Preventive Antibiotics in Stroke Study. Cerebrovascular Diseases 2016;42(5‐6):361‐9. - PMC - PubMed
Walter 2007
    1. Walter U, Knoblich R, Steinhagen V, Donat M, Benecke R, Kloth A. Predictors of pneumonia in acute stroke patients admitted to a neurological intensive care unit. Journal of Neurology 2007;254(10):1323‐9. - PubMed
Westendorp 2011
    1. Westendorp WF, Nederkoorn PJ, Vermeij JD, Dijkgraaf MG, Beek D. Post‐stroke infection: a systematic review and meta‐analysis. BMC Neurology 2011;20;11:100. - PMC - PubMed
Yilmaz 2007
    1. Yilmaz GR, Cevik MA, Erdinc FS, Ucler S, Tulek N. The risk factors for infections acquired by cerebral hemorrhage and cerebral infarct patients in a neurology intensive care unit in Turkey. Japanese Journal of Infectious Diseases 2007;60(2‐3):87‐91. - PubMed

References to other published versions of this review

Vermeij 2010
    1. Vermeij F, Nederkoorn PJ, Hertog HM, Beek D, Dippel DWJ. Antibiotic therapy for preventing infections in patients with acute stroke. Cochrane Database of Systematic Reviews 2010, Issue 6. [DOI: 10.1002/14651858.CD008530] - DOI - PubMed
Westendorp 2012
    1. Westendorp WF, Vermeij JD, Vermeij F, Hertog HM, Dippel DW, Beek D, et al. Antibiotic therapy for preventing infections in patients with acute stroke. Cochrane Database of Systematic Reviews 2012, Issue 1. [DOI: 10.1002/14651858.CD008530.pub2] - DOI - PubMed

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