- Céire Costelloe, research associate1,
- Chris Metcalfe, senior lecturer in medical statistics2,
- Andrew Lovering, consultant clinical scientist3,
- David Mant, professor of general practice4,
- Alastair D Hay, consultant senior lecturer in primary health care1
- 1Academic Unit of Primary Health Care, NIHR National School for Primary Care Research, Department of Community Based Medicine, University of Bristol, Bristol BS8 2AA
- 2Department of Social Medicine, Canynge Hall, University of Bristol, Bristol BS8 2PS
- 3Department of Microbiology, Bristol Centre for Antimicrobial Research and Enterprise, Southmead Hospital, Bristol BS9 3HU
- 4Department of Primary Health Care, NIHR National School for Primary Care Research, Oxford University, Headington, Oxford OX3 7LF
- Correspondence to: A Hay
- Accepted 19 March 2010
Objective To systematically review the literature and, where appropriate, meta-analyse studies investigating subsequent antibiotic resistance in individuals prescribed antibiotics in primary care.
Design Systematic review with meta-analysis.
Data sources Observational and experimental studies identified through Medline, Embase, and Cochrane searches.
Review methods Electronic searches using MeSH terms and text words identified 4373 papers. Two independent reviewers assessed quality of eligible studies and extracted data. Meta-analyses were conducted for studies presenting similar outcomes.
Results The review included 24 studies; 22 involved patients with symptomatic infection and two involved healthy volunteers; 19 were observational studies (of which two were prospective) and five were randomised trials. In five studies of urinary tract bacteria (14 348 participants), the pooled odds ratio (OR) for resistance was 2.5 (95% confidence interval 2.1 to 2.9) within 2 months of antibiotic treatment and 1.33 (1.2 to 1.5) within 12 months. In seven studies of respiratory tract bacteria (2605 participants), pooled ORs were 2.4 (1.4 to 3.9) and 2.4 (1.3 to 4.5) for the same periods, respectively. Studies reporting the quantity of antibiotic prescribed found that longer duration and multiple courses were associated with higher rates of resistance. Studies comparing the potential for different antibiotics to induce resistance showed no consistent effects. Only one prospective study reported changes in resistance over a long period; pooled ORs fell from 12.2 (6.8 to 22.1) at 1 week to 6.1 (2.8 to 13.4) at 1 month, 3.6 (2.2 to 6.0) at 2 months, and 2.2 (1.3 to 3.6) at 6 months.
Conclusions Individuals prescribed an antibiotic in primary care for a respiratory or urinary infection develop bacterial resistance to that antibiotic. The effect is greatest in the month immediately after treatment but may persist for up to 12 months. This effect not only increases the population carriage of organisms resistant to first line antibiotics, but also creates the conditions for increased use of second line antibiotics in the community.
Contributors: CC performed the searches. CC and ADH identified eligible studies. All authors appraised study quality and extracted data. CC and CM transformed data and performed the meta-analyses. CC and ADH drafted first sections of the text. All authors contributed to the final draft. ADH and CC are the guarantors. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis.
Funding: This work was undertaken by the University of Bristol in collaboration with the University of Oxford which both received a proportion of their funding from the Department of Health’s NIHR School for Primary Care Research. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health. The funder had no role in the study design; data collection, data analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. The researchers were independent of the funder.
Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that (1) CC, ADH, DM, AL, and CM have support from the Universities of Bristol and Oxford for the submitted work; (2) None of the authors has relationships with any companies that might have an interest in the submitted work in the previous 3 years; (3) None of the authors’ spouses, partners, or children have any financial relationships that may be relevant to the submitted work; and (4) None of the authors has any non-financial interests that may be relevant to the submitted work.
Ethical approval: Not required.
Data sharing: No additional data available.
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