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Centre for Clinical Practice at NICE (UK). Respiratory Tract Infections - Antibiotic Prescribing: Prescribing of Antibiotics for Self-Limiting Respiratory Tract Infections in Adults and Children in Primary Care. London: National Institute for Health and Clinical Excellence (UK); 2008 Jul. (NICE Clinical Guidelines, No. 69.)

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Respiratory Tract Infections - Antibiotic Prescribing: Prescribing of Antibiotics for Self-Limiting Respiratory Tract Infections in Adults and Children in Primary Care.

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3References, glossary and abbreviations

3.1. References

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  15. Dagnelie CF, VanderGraaf Y, DeMelker RA, et al. Do patients with sore throat benefit from penicillin - a randomized double-blind placebo-controlled clinical-trial with penicillin-v in general-practice. British Journal of General Practice. 1996;46:589–93. [PMC free article: PMC1239783] [PubMed: 8945796]
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  17. Davey P. Assessing the cost-effectiveness of antibiotic treatment of pharyngitis and acute otitis media. Current Therapeutic Research, Clinical and Experimental. 1994;55(Supplement A):2–13.
  18. de Bock GH, van Erkel AR, Springer MP, et al. Antibiotic prescription for acute sinusitis in otherwise healthy adults: clinical cure in relation to costs. Scandinavian Journal of Primary Health Care. 2001;19(1):58–63. [PubMed: 11303550]
  19. Del Mar CB, Glasziou PP, Spinks AB. Antibiotics for sore throat. Cochrane Database of Systematic Reviews. 2006;(4) Art. No.: CD000023. [PubMed: 17054126] [Cross Ref]
  20. Dippel DW, Touw-Otten F, Habbema JD. Management of children with acute pharyngitis: a decision analysis.[see comment] Journal of Family Practice. 1992;34:149–59. [PubMed: 1472174]
  21. Dowell J, Pitkethly M, Bain J, et al. A randomised controlled trial of delayed antibiotic prescribing as a strategy for managing uncomplicated respiratory tract infection in primary care. British Journal of General Practice. 2001;51:200–5. [PMC free article: PMC1313951] [PubMed: 11255901]
  22. Dunn N, Lane D, Everitt H, et al. Use of antibiotics for sore throat and incidence of quinsy. British Journal of General Practice. 2007;57:45–9. [PMC free article: PMC2032700] [PubMed: 17244424]
  23. Edwards M, Dennison J, Sedgwick P. Patients’ responses to delayed antibiotic prescription for acute upper respiratory tract infections. British Journal of General Practice. 2003;53:845–50. [PMC free article: PMC1314726] [PubMed: 14702903]
  24. Fahey T, Smucny J, Becker L, et al. Antibiotics for acute bronchitis. Cochrane Database of Systematic Reviews. 2004;(4) Art. No.: CD000245. [PubMed: 15494994] [Cross Ref]
  25. Fransen G, van Marrewijk C, Mujakovic S, et al. Pragmatic trials in primary care. Methodological challenges and solutions demonstrated by the DIAMOND-study. BMC Medical Research Methodology. 2007;7 [PMC free article: PMC1865384] [PubMed: 17451599]
  26. Fraser R. Clinical method: a general practice approach. 1999.
  27. Gerber MA, Randolph MF, DeMeo KK, et al. Lack of impact of early antibiotic therapy for streptococcal pharyngitis on recurrence rates. Journal of Pediatrics. 1990;117:853–8. [PubMed: 2123239]
  28. Gill P, Roalfe A. Antibiotic prescribing by single handed general practitioners: secondary analysis of data. Journal of Clinical Pharmacy and Therapeutics. 2001;26:195–9. [PubMed: 11422603]
  29. Gill P, Scrivener G, LLoyd D, et al. The effect of patient ethnicity on prescribing rates. Health Trends. 1996;27:111–4. [PubMed: 10162320]
  30. Glasziou PP, Del Mar CB, Sanders SL, et al. Antibiotics for acute otitis media in children. Cochrane Database of Systematic Reviews. 2004;(1) Art. No.: CD000219. [PubMed: 14973951] [Cross Ref]
  31. Godwin M, Ruhland L, Casson I, et al. Pragmatic controlled clinical trials in primary care: the struggle between external and internal validity. BMC Medical Research Methodology. 2003;3 [PMC free article: PMC317298] [PubMed: 14690550]
  32. Hay AD. Predicting complications from a acute cough in pre-school children in primary care: A prospective cohort study. British Journal of General Practice. 2004;54:9–14. [PMC free article: PMC1314771] [PubMed: 14965400]
  33. Hay AD, Gorst C, Montgomery A, et al. Validation of a clinical rule to predict complications of acute cough in preschool children: a prospective study in primary care. British Journal of General Practice. 2007;57:530–7. [PMC free article: PMC2099635] [PubMed: 17727745]
  34. Hayden JA, Cote P, Bombadier C. Evaluation of the quality of prognosis studies in systematic reviews. Annals of Internal Medicine. 2006;144:427–37. [PubMed: 16549855]
  35. Heikkinen T, Jarvinen A. The common cold. Lancet. 2003;361:51–9. [PubMed: 12517470]
  36. Hillner BE, Centor RM. What a difference a day makes: a decision analysis of adult streptococcal pharyngitis. Journal of General Internal Medicine. 1987;2:244–50. [PubMed: 3302145]
  37. Koskinen H, Rautakorpi UM, Sintonen H, et al. Cost-effectiveness of implementing national guidelines in the treatment of acute otitis media in children. International Journal of Technology Assessment in Health Care. 2006;22(4):454–9. [PubMed: 16984678]
  38. Lindbaek M. Prescribing antibiotics to patients with acute cough and otitis media. British Journal of General Practice. 2006;56:164–5. [PMC free article: PMC1828256] [PubMed: 16536953]
  39. Little P, Watson L, Morgan S, et al. Antibiotic prescribing and admissions with major suppurative complications of respiratory tract infections: a data linkage study. British Journal of General Practice. 2002;52:187–93. [PMC free article: PMC1314237] [PubMed: 12030660]
  40. Little P. Delayed prescribing of antibiotics for upper respiratory tract infection. BMJ. 2005;331:301–2. [PMC free article: PMC1183117] [PubMed: 16081428]
  41. Little P, Gould C, Williamson I, et al. Pragmatic randomised controlled trial of two prescribing strategies for childhood acute otitis media. BMJ. 2001;322:336–42. [PMC free article: PMC26576] [PubMed: 11159657]
  42. Little P, Moore M, Warner G, et al. Longer term outcomes from a randomised trial of prescribing strategies in otitis media. British Journal of General Practice. 2006;56:176–82. [PMC free article: PMC1828260] [PubMed: 16536957]
  43. Little P, Rumsby K, Kelly J, et al. Information leaflet and antibiotic prescribing strategies for acute lower respiratory tract infection: a randomized controlled trial. JAMA: Journal of the American Medical Association. 2005;293:3029–35. [PubMed: 15972565]
  44. Little P, Williamson I, Warner G, et al. Open randomised trial of prescribing strategies in managing sore throat. BMJ. 1997;314:722–7. [PMC free article: PMC2126131] [PubMed: 9116551]
  45. Macfarlane J, Holmes W, Gard P, et al. Reducing antibiotic use for acute bronchitis in primary care: blinded, randomised controlled trial of patient information leaflet. BMJ. 2002;324:91–4. [PMC free article: PMC64506] [PubMed: 11786454]
  46. Macfarlane JT, Holmes WF, Macfarlane RM. Reducing reconsultations for acute lower respiratory tract illness with an information leaflet: a randomized controlled study of patients in primary care. British Journal of General Practice. 1997;47:719–22. [PMC free article: PMC1409927] [PubMed: 9519518]
  47. McCormick DP, Chonmaitree T, Pittman C, et al. Nonsevere acute otitis media: a clinical trial comparing outcomes of watchful waiting versus immediate antibiotic treatment. Pediatrics. 2005;115:1455–65. [PubMed: 15930204]
  48. McNulty C, Boyle P, Nichols T, et al. Don’t wear me out - the public’s knowledge of and attitudes to antibiotic use. Journal of Antimicrobial Chemotherapy. 2007;59:727–38. [PubMed: 17307770]
  49. Morris P, Leach A. Antibiotics for persistent nasal discharge (rhinosinusitis) in children. Cochrane Database of Systematic Reviews. 2002;(3) Art. No.: CD001094. [PubMed: 12519551] [Cross Ref]
  50. Neuner JM, Hamel MB, Phillips RS, et al. Diagnosis and management of adults with pharyngitis: a cost effectiveness analysis. Annals of Internal Medicine. 2003;139(2):113–22. [PubMed: 12859161]
  51. Petersen I, Johnson AM, Duckworth G, et al. Protective effect of antibiotics against serious complications of common respiratory tract infections: retrospective cohort study with the UK General Practice Research Database. BMJ. 2007;335:982. [PMC free article: PMC2072032] [PubMed: 17947744]
  52. Pichichero ME, Disney FA, Talpey WB, et al. Adverse and beneficial effects of immediate treatment of Group A beta-hemolytic streptococcal pharyngitis with penicillin. Pediatric Infectious Disease Journal. 1987;6:635–43. [PubMed: 3302916]
  53. Pshetizky Y, Naimer S, Shvartzman P. Acute otitis media - a brief explanation to parents and antibiotic use. Family Practice. 2003;20:417–9. [PubMed: 12876113]
  54. Rovers MM, Glasziou P, Appelman CL, et al. Antibiotics for acute otitis media: a meta-analysis with individual patient data. Lancet. 2006;368:1429–35. [PubMed: 17055944]
  55. Singh S, Dolan JG, Centor RM. Optimal management of adults with pharyngitis--a multi-criteria decision analysis. BMC Medical Informatics & Decision Making. 2006;6:14. [PMC free article: PMC1431519] [PubMed: 16533386]
  56. Spiro DM, Tay KY, Arnold DH, et al. Wait-and-see prescription for the treatment of acute otitis media: a randomized controlled trial. JAMA: Journal of the American Medical Association. 2006;296:1235–41. [PubMed: 16968847]
  57. Spurling G, Del Mar C, Dooley L, et al. Delayed antibiotics for respiratory infections. Cochrane Database of Systematic Reviews. 2007;(3) Art. No.: CD004417. [PubMed: 17636757] [Cross Ref]
  58. Standing Medical Advisory Committee, Sub-Group on Antimicrobial Resistance. The path of least resistance. 1998. [London]: [Department of Health]
  59. Stewart A, Philips RJM. Antibiotic treatment for paediatric streptococcal pharyngitis: estimation of costs in general practice. British Journal of Medical Economics. 1994;7:123–136.
  60. Tsevat J, Kotagal UR. Management of sore throats in children: a cost-effectiveness analysis. Archives of Pediatrics and Adolescent Medicine. 1999;153(7):681–8. [PubMed: 10401800]
  61. van Buchem Peeters M, van T, Hof M. Acute otitis media a new treatment strategy. BMJ. 1985;290:1033–7. [PMC free article: PMC1418336] [PubMed: 3921097]
  62. Van Howe RS, Kusnier LP. Diagnosis and management of pharyngitis in a pediatric population based on cost-effectiveness and projected health outcomes. Pediatrics. 2006;117(3):609–19. [PubMed: 16510638]
  63. Williams JW Jr, Aguilar C, Cornell J, et al. Antibiotics for acute maxillary sinusitis. Cochrane Database of Systematic Reviews. 2003;(2) Art. No.: CD000243. [PubMed: 12804392] [Cross Ref]
  64. Williamson IG, Rumsby K, Benge S, et al. Antibiotics and topical nasal steroid for treatment of acute maxillary sinusitis. JAMA: Journal of the American Medical Association. 2007;298:2487–96. [PubMed: 18056902]
  65. Young J, De Sutter A, Merenstein D, et al. Antibiotics for adults with clinically diagnosed acute rhinosinusitis: a meta-analysis of individual patient data. Lancet. 2008;371:908–14. [PubMed: 18342685]
  66. Zwart S, Sachs APE, Ruijs GJHM, et al. Penicillin for acute sore throat: randomised double blind trial of seven days versus three days treatment or placebo in adults. BMJ. 2000;320:150–4. [PMC free article: PMC27262] [PubMed: 10634735]

3.2. Glossary

Respiratory tract infection

RTI is defined as any infectious disease of the upper or lower respiratory tract. Upper respiratory tract infections (URTIs) include the common cold, laryngitis, pharyngitis/tonsillitis, rhinitis, rhinosinusitis/sinusitis and otitis media. Lower respiratory tract infections (LRTIs) include bronchitis, bronchiolitis, pneumonia and tracheitis. The five common respiratory tract infections that are covered by this guideline are: the common cold, pharyngitis/tonsillitis, rhinosinusitis/sinusitis, acute otitis media and acute cough/acute bronchitis.

Centor criteria

The Centor criteria have been developed to predict bacterial infection in acute sore throat. The four Centor criteria are: presence of tonsillar exudate, tender anterior cervical lymphadenopathy or lymphadenitis, history of fever and an absence of cough. (Centor et al. 1981).

Before-and-after study

A study design that involves intervention and control groups chosen other than by random process, and inclusion of a baseline period of assessment of main outcomes. There are two minimum criteria for this study design: that the pre- and post-intervention periods for the study sites and the control sites are the same, and that second sites used as control sites are comparable with the control sites in terms of dominant reimbursement system, level of care, setting of care and academic status.

Case control study

A comparative observational study in which the investigator selects individuals who have experienced an event (for example, developed a disease) and others who have not (controls), and then collects data to determine previous exposure to a possible cause.

Cohort study

An observational study in which a defined group of people (the cohort) is followed over time (also known as a follow-up, incidence, longitudinal or prospective study). Outcomes are compared in subsets of the cohort who were exposed or not exposed (or exposed at different levels) to an intervention or other factor of interest.


Two or more diseases or conditions occurring at the same time, such as depression and anxiety.

Confidence interval

The range within which the ‘true‘ values (for example, size of effect of an intervention) are expected to lie with a given degree of certainty (for example, 95% or 99%). (Note: confidence intervals represent the probability of random errors, but not systematic errors or bias.)

Cost-effectiveness analysis

An economic evaluation that compares alternative options for a specific patient group, looking at a single effectiveness dimension measured in a non-monetary (natural) unit. It expresses the result in the form of an incremental (or average or marginal) cost-effectiveness ratio.

Economic evaluation

A technique developed to assess both the costs and the consequences of alternative health strategies and to provide a decision-making framework.

Extendedly dominated

A term used in health economics. An extendedly dominated strategy has an ICER (incremental cost-effectiveness ratio) higher than that of the next most effective strategy; therefore an extendedly dominated strategy produces additional gains in effectiveness at incremental costs higher than those of the next most effective strategy.

Guideline Development Group

A group of healthcare professionals, patients, carers and members of the Short Clinical Guidelines Technical Team who develop the recommendations for a short clinical guideline. The group writes draft guidance, and then revises it after a consultation with organisations registered as stakeholders.


The degree to which the results of a study or systematic review can be extrapolated to other circumstances, particularly routine healthcare situations in the NHS in England and Wales.


Grading of Recommendations Assessment, Development and Evaluation is a system for grading the quality of evidence and the strength of recommendations that can be applied across a wide range of interventions and contexts.


A term used to illustrate the variability or differences between studies in the estimates of effects.


Kappa coefficient is a statistical measure of inter-rater reliability. It is generally thought to be a more robust measure than simple per cent agreement calculation because kappa takes into account the agreement occurring by chance.

Likelihood ratio

The likelihood ratio incorporates both the sensitivity and specificity of the test and provides a direct estimate of how much a test result will change the odds of having a disease. The likelihood ratio for a positive result (LR+) tells you how much the odds of the disease increase when a test is positive. The likelihood ratio for a negative result (LR−) tells you how much the odds of the disease decrease when a test is negative.

Negative predictive value

The proportion of patients with negative test results who are correctly diagnosed.

Number needed to treat

The number needed to treat (NNT) is defined as the expected number of people who need to receive the experimental rather than the comparator intervention for one additional person to either incur (or avoid) an event in a given time frame. Thus, for example, an NNT of 10 can be interpreted as ‘it is expected that one additional (or less) person will incur an event for every 10 participants receiving the experimental intervention rather than control over a given time frame’. It is important to be clear that:

  • since the NNT is derived from the risk difference, it is still a comparative measure of effect (experimental versus a certain control) and not a general property of a single intervention; and
  • the NNT gives an ‘expected value’. For example, NNT = 10 does not imply that one additional event will occur in each and every group of ten people.

Odds ratio

A measure of treatment effectiveness. The odds of an event happening in the intervention group, divided by the odds of it happening in the control group. The ‘odds’ is the ratio of non-events to events.

Positive predictive value

The proportion of people with a positive test result who actually have the disease.

Purposive sampling

A purposive sample is one that is selected by the researcher subjectively. The researcher attempts to obtain a sample that appears to him/her to be representative of the population and will usually try to ensure that a range from one extreme to the other is included.

Quality-adjusted life year

A statistical measure, representing 1 year of life, with full quality of life.

Randomised controlled trial

A form of clinical trial to assess the effectiveness of medicines or procedures. Considered reliable because it tends not to be biased.

Relative risk

Also known as risk ratio; the ratio of risk in the intervention group to the risk in the control group. The risk (proportion, probability or rate) is the ratio of people with an event in a group to the total in the group. A relative risk (RR) of 1 indicates no difference between comparison groups. For undesirable outcomes, an RR below 1 indicates that the intervention was effective in reducing the risk of that outcome.

Receiver operating characteristic

Receiver operating characteristic (ROC), or simply ROC curve, is a graphical plot of the sensitivity vs. (1 – specificity) for a classifier system as its discrimination threshold is varied. The ROC can also be represented equivalently by plotting the fraction of true positives (TPR = true positive rate) vs. the fraction of false positives (FPR = false positive rate).

Sensitivity (of a test)

The proportion of people classified as positive by the gold standard who are correctly identified by the study test.

Specificity (of a test)

The proportion of people classified as negative by the gold standard who are correctly identified by the study test.

Systematic review

Research that summarises the evidence on a clearly formulated question according to a predefined protocol using systematic and explicit methods to identify, select and appraise relevant studies, and to extract, collate and report their findings. It may or may not use statistical meta-analysis.

3.3. Abbreviations


Acute otitis media


Confidence interval


Chronic obstructive pulmonary disease


Group A beta-haemolytic Streptococcus


General Practice Research Database


Grading of Recommendations Assessment, Development and Evaluation


International Classification of Health Problems in Primary Care - 2


Individual patient data meta-analysis


Likelihood ratio


Lower respiratory tract infection


Negative predictive value


Not significant


Number needed to treat


Positive predictive value


Odds ratio


Quality-adjusted life year


Respiratory tract infection


Receiver operating characteristic


Randomised controlled trial


Relative risk


Standard deviation


Upper respiratory tract infection

Copyright © 2008, National Institute for Health and Clinical Excellence.

All rights reserved. This material may be freely reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the express written permission of the Institute.

Bookshelf ID: NBK53640


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