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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Effectiveness of antibiotics given before admission in reducing mortality from meningococcal disease: systematic review

SJ Hahne, A Charlett, B Purcell, S Samuelsson, I Camaroni, I Ehrhard, S Heuberger, M Santamaria, and JM Stuart.

Review published: 2006.

CRD summary

This review assessed whether antibiotics given before hospital admission reduce mortality from meningitis. The authors concluded that the available studies cannot answer the question because there are likely to be systematic differences in disease severity between treated and untreated groups. The conclusion that the true effect of treatment is uncertain reflects the limitations of the evidence and appears reliable.

Authors' objectives

To determine the effectiveness of treatment with antibiotics before hospital admission in reducing mortality from meningococcal disease.


The authors searched the Cochrane CENTRAL Register and Database of Systematic Reviews, DARE, HTA, the National Research Register for England and Wales, MEDLINE, EMBASE and CAB Health (from inception to 31 January 2005). The search terms used were reported and no language restrictions were applied. Bibliographies of existing reviews were checked, and groups and organisations active in the field of infectious disease were contacted.

Study selection

Study designs of evaluations included in the review

Except for the requirement that studies include at least 10 patients, inclusion criteria for the study design were not specified. All of the included studies were observational cohort studies.

Specific interventions included in the review

Studies of treatment with parenteral (intravenous or intramuscular) or oral antibiotics were eligible for inclusion. Parenteral and oral treatments were considered separately.

Participants included in the review

The participants were patients with meningococcal disease. Most studies included in the review included both microbiologically confirmed and clinically diagnosed cases. No further details of the participants were reported.

Outcomes assessed in the review

The included studies were required to report numbers of deaths among treated and untreated participants.

How were decisions on the relevance of primary studies made?

Two reviewers independently assessed studies for relevance.

Assessment of study quality

The authors did not state that they assessed validity.

Data extraction

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction. Data on the numbers of deaths, stratified by treatment before admission, were extracted and used to calculate unadjusted risk ratios (RRs). In studies presenting data on both oral and parenteral antibiotic treatments, patients treated with oral antibiotics were classified as untreated in analysing the effect of parenteral antibiotics.

Methods of synthesis

How were the studies combined?

The studies were combined by meta-analysis using a random-effects model.

How were differences between studies investigated?

Statistical heterogeneity between the studies was assessed using the chi-squared and I-squared statistics. Differences between the studies were also investigated by meta-regression, using the proportion of cases treated with parenteral antibiotics before admission and the proportion of cases classified as severe as covariates.

Results of the review

Fourteen observational cohort studies were included. Five studies (n=1,245) provided data on oral treatment and 12 studies (n=3,357) provided data on parenteral treatment.

Oral antibiotic treatment was associated with significantly reduced mortality (5 studies; combined RR 0.17, 95% confidence interval: 0.07, 0.44). Statistical heterogeneity was not significant.

For parenteral antibiotics, 8 studies showed a beneficial effect (one significant) and four a harmful effect of treatment. Significant heterogeneity was present among these 12 studies and among the 7 studies that only included patients seen in primary care before admission. In the 5 studies that included data stratified by severity of disease, the proportion of cases classified as severe ranged from 11 to 76%. Statistical heterogeneity was significant (P=0.02). None of the studies showed a statistically significant effect on mortality.

The meta-regression indicated that differences in the proportion of cases treated accounted for 100% of the variance between studies of parenteral antibiotics. There was a significant negative association (P=0.04) between the proportion of patients given parenteral antibiotics before admission and mortality after such treatment.

Authors' conclusions

Confounding by severity (systematic differences in disease severity between treated and untreated groups) is the most likely explanation for the beneficial effects of oral antibiotics and the harmful effects seen in some studies with parenteral antibiotics. In view of this it is uncertain whether antibiotics given before admission affect mortality. The data are consistent with benefit when a substantial proportion of patients are treated.

CRD commentary

The review addressed a clear question and had clear inclusion criteria, although criteria for the study designs were not explicitly stated. The authors searched a range of appropriate sources without language restrictions and made efforts to locate unpublished material. Measures were taken to reduce errors and bias in the study selection process (two independent reviewers), although methods used in the data extraction were not reported. Validity was not formally assessed and few details of treatments and participants were provided, but these factors are unlikely to affect the reliability of the authors' cautious conclusions. The data were synthesised by meta-analysis and the authors made a thorough assessment of possible sources of heterogeneity. The authors' conclusion, that the true effect of treatment is uncertain, reflects the limitations of the available evidence and appears reliable.

Implications of the review for practice and research

Practice: The authors did not state any implications for practice.

Research: The authors stated that randomised controlled trials are needed to give reliable evidence of the effects of antibiotic treatment on survival, but such trials may never be carried out because of expected logistical and ethical difficulties.

Bibliographic details

Hahne S J, Charlett A, Purcell B, Samuelsson S, Camaroni I, Ehrhard I, Heuberger S, Santamaria M, Stuart J M. Effectiveness of antibiotics given before admission in reducing mortality from meningococcal disease: systematic review. BMJ 2006; 332: 1299. [PMC free article: PMC1473099] [PubMed: 16740557]

Indexing Status

Subject indexing assigned by NLM


Administration, Oral; Anti-Bacterial Agents /administration & dosage; Emergency Medical Services /statistics & numerical data; Hospitalization /statistics & numerical data; Humans; Infusions, Parenteral; Meningococcal Infections /drug therapy /mortality; Risk Factors; Treatment Outcome



Database entry date


Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 16740557

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