A practical tool for primary care antimicrobial stewardship in children
Authors: Christopher C Winchester, Alison Chisholm, David Price
Journal: The Lancet Respiratory Medicine (2016)

Respiratory tract infections are the single most important cause of consultations in primary care.1McCormick A Fleming D Charlton J Morbidity statistics from general practice: fourth national study, 1991–92. Series MB5 no 3.http://webarchive.nationalarchives.gov.uk/20040119062427/http://www.statistics.gov.uk/downloads/theme_health/MB5No3.pdfGoogle Scholar Approximately 60% of 0–4 year-olds and 30% of 5–15 year-olds present with an acute respiratory infection at least once a year,1McCormick A Fleming D Charlton J Morbidity statistics from general practice: fourth national study, 1991–92. Series MB5 no 3.http://webarchive.nationalarchives.gov.uk/20040119062427/http://www.statistics.gov.uk/downloads/theme_health/MB5No3.pdfGoogle Scholar positioning the primary care consultation for respiratory tract infection as a high-profile target for antimicrobial stewardship initiatives. However, despite national and international calls for more targeted use,2Department of HealthUK Five Year Antimicrobial Resistance Strategy 2013 to 2018. In: Health Do, ed 2013.http://www.gov.uk/government/uploads/system/uploads/attachment_data/file/244058/20130902_UK_5_year_AMR_strategy.pdfGoogle Scholar primary care prescription of antibiotics for coughs and colds increased by 40% in the UK between 1999 and 2011,3Hawker JI Smith S Smith GE et al.Trends in antibiotic prescribing in primary care for clinical syndromes subject to national recommendations to reduce antibiotic resistance, UK 1995–2011: analysis of a large database of primary care consultations.J Antimicrob Chemother. 2014; 69: 3423-3430Crossref PubMed Scopus (114) Google Scholar in part reflecting the uncertainties facing patients, parents, and health-care professionals when managing these common but potentially life-threatening infections. Safety assessments of no antibiotic prescription initiatives for respiratory tract infections will play an important part in gaining public acceptance and successful uptake in practice.4Huttner B Goossens H Verheij T Harbarth S CHAMP consortium. Characteristics and outcomes of public campaigns aimed at improving the use of antibiotics in outpatients in high-income countries.Lancet Infect Dis. 2010; 10: 17-31Summary Full Text Full Text PDF PubMed Scopus (317) Google Scholar Present evidence remains equivocal, suggesting that insufficiently informed reductions in antibiotic prescription in primary care might increase rates of pneumonia diagnosis,5Petersen I Johnson AM Islam A 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: 982Crossref PubMed Scopus (207) Google Scholar hospital admissions, and even mortality.6Winchester CC Macfarlane TV Thomas M Price D Antibiotic prescribing and outcomes of lower respiratory tract infection in UK primary care.Chest. 2009; 135: 1163-1172Summary Full Text Full Text PDF PubMed Scopus (41) Google Scholar Yet decreased prescribing rates have also been shown to have little effect on rates of rare complications such as mastoiditis, empyema, meningitis, intracranial abscess, and Lemierre's syndrome.5Petersen I Johnson AM Islam A 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: 982Crossref PubMed Scopus (207) Google Scholar Tools that inform antibiotic use according to individualised patient risk profiles could help to realise the benefits of antibiotic stewardship programmes in primary care while minimising potential risks. In The Lancet Respiratory Medicine, Hay and colleagues7Hay AD Redmond NM Turnbull S et al.Development and internal validation of a clinical rule to improve antibiotic use in children presenting to primary care with acute respiratory tract infection and cough: a prognostic cohort study.Lancet Respir Med. 2016; (published online Sept 1.)http://dx.doi.org/10.1016/S2213-2600(16)30223-5PubMed Google Scholar report the results of a prognostic cohort study to devise a clinical prediction rule to target antibiotic prescribing in children with respiratory tract infections. The aim was to derive (and validate) a clinical prediction rule to improve targeted antibiotic prescribing in children with respiratory tract infections. The study included 8394 children aged 3 months to 15 years presenting with acute cough and respiratory tract infection to 247 general practices in England. Risk of hospital admission in the month after presentation in primary care was assessed. Exposure variables included demographic characteristics, parent-reported symptoms, and physical examination signs. More than a third (3121) of the children were prescribed an antibiotic on the day of consultation, and 78 (1%) were admitted to hospital with a respiratory tract infection in the following 30 days. Irrespective of antibiotic prescription, seven characteristics were independently associated (p<0·01) with hospital admission. This statistical analysis underpinned the creation of a seven-item points-based checklist (one point per item) comprising characteristics easily assessable at the point of care: short illness duration (≤3 days); body temperature; age (<2 years); recession; wheeze; asthma; and vomiting (STARWAVe). Using the STARWAVe mnemonic to help structure point-of-care assessment of children presenting with cough and respiratory tract infection should predict the risk of hospital admission with remarkable accuracy (area under the received operating characteristic curve 0·81, 95%CI 0·76–0·85). Because the statistical model used to produce the STARWAVe checklist included children prescribed antibiotics (37% of the total study population), it does not reflect the baseline risk of hospital admission in patients not treated with antibiotics. Children with a diagnosis of asthma, who accounted for nearly 10% (750) of the total population, were also included in the study. The fact that asthma was the strong predictor of hospital admission in the STARWAVe checklist despite its presence in only 10% of the patient population could reflect the magnitude of effect of comorbid obstructive airway disease on hospital admission for respiratory tract infection in this young population. Without a separate analysis, it is difficult to know explicitly how well the tool works in the majority, non-asthmatic subpopulation. Validation of the model was only feasible via statistical methods (bootstrapping) with the full scope of intended validation limited by the lower-than-expected hospital admission rate and a consequent lack of statistical power. External validation is important, because (despite high enrolment rates) the study population did not include 164 children whose parents did not consent to the study; consequently, the small minority of severely ill children might not have been fully represented in the study population (only 204 of whom had a STARWAVe score of 4–7). Yet validation attempts using clinical or research databases will be thwarted if, as seems likely, the full range of STARWAVe variables are not collected routinely. A pragmatic alternative might be a prospective pilot study assessing the within-practice effect of future versus historical outcomes (ideally compared with best practice comparator sites to take account of temporal variations in respiratory tract infection), or a cluster randomised trial. Notwithstanding the inclusion of patients prescribed an antibiotic and the absence of an independent validation cohort, STARWAVe promises to achieve better targeting of antibiotics in primary care. There are few efficacious interventions for respiratory tract infection available to primary care clinicians beyond offering reassurance and self-management advice, so the modest benefit offered by antibiotics8National Institute for Health and Care ExcellenceRespiratory tract infections (self-limiting): prescribing antibiotics. NICE guidelines CG69.https://www.nice.org.uk/guidance/cg69/chapter/introductionGoogle Scholar can persuade general practitioners to prescribe them. STARWAVe offers primary care clinicians an evidence-based practical tool to help guide antibiotic prescription decisions and, through shared decision-making, has the potential to reduce antibiotic prescription based on prognostic uncertainty or on non-medical grounds.9Horwood J Cabral C Hay AD Ingram J Primary care clinician antibiotic prescribing decisions in consultations for children with RTIs: a qualitative interview study.Br J Gen Pract. 2016; 66: e207-e213Crossref PubMed Scopus (69) Google Scholar Combining this tool with point-of-care C-reactive protein (CRP) testing, or to triage for CRP testing,10Aabenhus R Jensen JU Jørgensen KJ Hróbjartsson A Bjerrum L Biomarkers as point-of-care tests to guide prescription of antibiotics in patients with acute respiratory infections in primary care.Cochrane Database Syst Rev. 2014; 11 (CD010130)Google Scholar might help to target antibiotic use further. If STARWAVe leads to an increase in antibiotic prescription (to 90%) in high-risk children and a parallel halving of prescription to those at low risk of hospital admission, it could achieve a 10% overall reduction in primary care antibiotic prescriptions for respiratory tract infections. Within the wider context, the effect of such outcomes on the global burden of antimicrobial resistance will depend on the extent to which its emergence and spread is truly associated with community prescribing as opposed to antibiotic use in hospitals or agriculture.11Holmes AH Moore LS Sundsfjord A et al.Understanding the mechanisms and drivers of antimicrobial resistance.Lancet. 2016; 387: 176-187Summary Full Text Full Text PDF PubMed Scopus (1139) Google Scholar CCW reports shareholding from Oxford PharmaGenesis, AstraZeneca, and Shire Pharmaceuticals, outside the submitted work. DP reports other from Aerocrine, Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Meda, Aerocrine, Almirall, Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Meda, Merck & Co, Mundipharma, Napp, Novartis International AG, Pfizer, Skyepharma, Takeda, Teva, and Zentiva; and grants from UK National Health Service, British Lung Foundation, Aerocrine, AKL, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Eli Lilly, GlaxoSmithKline, Meda, Merck & Co., Mundipharma, Napp, Novartis International AG, Orion, Pfizer, Respiratory Effectiveness Group, Takeda, Teva, and Zentiva, outside of the submitted work. AC declares no competing interests. Development and internal validation of a clinical rule to improve antibiotic use in children presenting to primary care with acute respiratory tract infection and cough: a prognostic cohort studyClinical characteristics can distinguish children at very low, normal, and high risk of future hospital admission for respiratory tract infection and could be used to reduce antibiotic prescriptions in primary care for children at very low risk. Full-Text PDF Open Access