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Antibiotic treatment failure in four common infections in UK primary care 1991-2012: longitudinal analysis

BMJ 2014; 349 doi: (Published 23 September 2014) Cite this as: BMJ 2014;349:g5493
  1. Craig J Currie, professor12,
  2. Ellen Berni, scientific officer2,
  3. Sara Jenkins-Jones, research fellow2,
  4. Chris D Poole, senior research associate1,
  5. Mario Ouwens, principal statistician3,
  6. Stefan Driessen, head, biometrics3,
  7. Hanka de Voogd, head, therapeutic area3,
  8. Christopher C Butler, professor14,
  9. Christopher Ll Morgan, epidemiologist2
  1. 1Cochrane Institute of Primary Care and Public Health, Cardiff University, Cardiff, UK
  2. 2Global Epidemiology, Pharmatelligence, Cardiff, UK
  3. 3Established Pharmaceuticals, Abbott Healthcare Products, Weesp, Netherlands
  4. 4Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
  1. Correspondence to: C J Currie currie{at}
  • Accepted 27 August 2014


Objective To characterise failure of antibiotic treatment in primary care in the United Kingdom in four common infection classes from 1991 to 2012.

Design Longitudinal analysis of failure rates for first line antibiotic monotherapies associated with diagnoses for upper and lower respiratory tract infections, skin and soft tissue infections, and acute otitis media.

Setting Routine primary care data from the UK Clinical Practice Research Datalink (CPRD).

Main outcome measures Adjusted rates of treatment failure defined by standardised criteria and indexed to year 1 (1991=100).

Results From 58 million antibiotic prescriptions in CPRD, we analysed 10 967 607 monotherapy episodes for the four indications: 4 236 574 (38.6%) for upper respiratory tract infections; 3 148 947 (28.7%) for lower respiratory tract infections; 2 568 230 (23.4%) for skin and soft tissue infections; and 1 013 856 (9.2%) for acute otitis media. In 1991, the overall failure rate was 13.9% (12.0% for upper respiratory tract infections; 16.9% for lower respiratory tract infections; 12.8% for skin and soft tissue infections; and 13.9% for acute otitis media). By 2012, the overall failure rate was 15.4%, representing an increase of 12% compared with 1991 (adjusted value indexed to first year (1991) 112, 95% confidence interval 112 to 113). The highest rate was seen in lower respiratory tract infections (135, 134 to 136). While failure rates were below 20% for most commonly prescribed antibiotics (amoxicillin, phenoxymethylpenicillin (penicillin-V), and flucloxacillin), notable increases were seen for trimethoprim in the treatment of upper respiratory tract infections (from 29.2% in 1991-95 to 70.1% in 2008-12) and for ciprofloxacin (from 22.3% in 1991-95 to 30.8% in 2008-12) and cefalexin (from 22.0% in 1991-95 to 30.8% in 2008-12) in the treatment of lower respiratory tract infections. Failure rates for broad spectrum penicillins, macrolides, and flucloxacillin remained largely stable.

Conclusions From 1991 to 2012, more than one in 10 first line antibiotic monotherapies for the selected infections were associated with treatment failure. Overall failure rates increased by 12% over this period, with most of the increase occurring in more recent years, when antibiotic prescribing in primary care plateaued and then increased.


  • We thank Monica S Rocha of Abbott Healthcare Products for her help with the figures and in critically reviewing the manuscript.

  • Contributors: CJC, CDP, and MO developed the study protocol. Data extraction and analysis were carried out by EB and SJJ, supervised by CJC. CDP created the Read code lists. CCB advised on the study question, analysis plan, and interpretation of the study findings, and contributed to drafting the final report. CLlM provided statistical expertise. Because of the conditions of the data licence, co-authors from the funding body did not have access to the source data from the Clinical Practice Research Datalink, though they did have access to processed data. All other authors had full access to all of the data (including statistical reports and tables) in the study. All authors contributed to, read, and approved the final manuscript, and all authors take responsibility for the integrity of the data and the accuracy of the data analysis. CJC is guarantor.

  • Funding: The study was funded by Abbott Healthcare Products. Co-authors from the funding body helped design the study and suggested editorial changes.

  • Competing interests: All authors have completed the Unified Competing Interest form at (available on request from the corresponding author) and declare that CDP and CLlM are contractors of, EB and SJJ are employed by, and CJC is a director of Pharmatelligence, a research consultancy receiving funding from Abbott Healthcare Products for the submitted work and from other healthcare related organisations; HDV, MO, and SD are employed by Abbott Healthcare Products; and CCB has received a research grant in kind from Alere in support of a publically funded study of COPD and has received honorariums from Alere and the Alliance for the Prudent Use of Antibiotics for presentations on point-of-care testing and diagnostics in primary care.

  • Ethical approval: Studies using the Clinical Practice Research Datalink are covered by ethics approval granted by the Trent multicentre research ethics committee (ref 05/MRE04/87). This study was approved by the Clinical Practice Research Datalink’s independent scientific advisory committee on 31 October 2013, protocol No 13_168R.

  • Data sharing: No additional data available. The study data remain the property of the Clinical Practice Research Datalink, provided to the authors under licence.

  • Transparency: CJC (the manuscript’s guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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