Alastair D Hay

Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis

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.

Paracetamol plus ibuprofen for the treatment of fever in children (PITCH): randomised controlled trial

Objective To investigate whether paracetamol (acetaminophen) plus ibuprofen are superior to either drug alone for increasing time without fever and the relief of fever associated discomfort in febrile children managed at home. Design Individually randomised, blinded, three arm trial. Setting Primary care and households in England. Participants Children aged between 6 months and 6 years with axillary temperatures of at least 37.8°C and up to 41.0°C. Intervention Advice on physical measures to reduce temperature and the provision of, and advice to give, paracetamol plus ibuprofen, paracetamol alone, or ibuprofen alone. Main outcome measures Primary outcomes were the time without fever (<37.2°C) in the first four hours after the first dose was given and the proportion of children reported as being normal on the discomfort scale at 48 hours. Secondary outcomes were time to first occurrence of normal temperature (fever clearance), time without fever over 24 hours, fever associated symptoms, and adverse effects. Results On an intention to treat basis, paracetamol plus ibuprofen were superior to paracetamol for less time with fever in the first four hours (adjusted difference 55 minutes, 95% confidence interval 33 to 77; P<0.001) and may have been as good as ibuprofen (16 minutes, −7 to 39; P=0.2). For less time with fever over 24 hours, paracetamol plus ibuprofen were superior to paracetamol (4.4 hours, 2.4 to 6.3; P<0.001) and to ibuprofen (2.5 hours, 0.6 to 4.4; P=0.008). Combined therapy cleared fever 23 minutes (2 to 45; P=0.025) faster than paracetamol alone but no faster than ibuprofen alone (−3 minutes, 18 to −24; P=0.8). No benefit was found for discomfort or other symptoms, although power was low for these outcomes. Adverse effects did not differ between groups. Conclusion Parents, nurses, pharmacists, and doctors wanting to use medicines to supplement physical measures to maximise the time that children spend without fever should use ibuprofen first and consider the relative benefits and risks of using paracetamol plus ibuprofen over 24 hours. Trial registration Current Controlled Trials ISRCTN26362730.

Duration of symptoms of respiratory tract infections in children: systematic review.

Objective To determine the expected duration of symptoms of common respiratory tract infections in children in primary and emergency care. Design Systematic review of existing literature to determine durations of symptoms of earache, sore throat, cough (including acute cough, bronchiolitis, and croup), and common cold in children. Data sources PubMed, DARE, and CINAHL (all to July 2012). Eligibility criteria for selecting studies Randomised controlled trials or observational studies of children with acute respiratory tract infections in primary care or emergency settings in high income countries who received either a control treatment or a placebo or over-the-counter treatment. Study quality was assessed with the Cochrane risk of bias framework for randomised controlled trials, and the critical appraisal skills programme framework for observational studies. Main outcome measures Individual study data and, when possible, pooled daily mean proportions and 95% confidence intervals for symptom duration. Symptom duration (in days) at which each symptom had resolved in 50% and 90% of children. Results Of 22 182 identified references, 23 trials and 25 observational studies met inclusion criteria. Study populations varied in age and duration of symptoms before study onset. In 90% of children, earache was resolved by seven to eight days, sore throat between two and seven days, croup by two days, bronchiolitis by 21 days, acute cough by 25 days, common cold by 15 days, and non-specific respiratory tract infections symptoms by 16 days. Conclusions The durations of earache and common colds are considerably longer than current guidance given to parents in the United Kingdom and the United States; for other symptoms such as sore throat, acute cough, bronchiolitis, and croup the current guidance is consistent with our findings. Updating current guidelines with new evidence will help support parents and clinicians in evidence based decision making for children with respiratory tract infections.

Interventions to influence consulting and antibiotic use for acute respiratory tract infections in children: a systematic review and meta-analysis.

Background Respiratory tract infections (RTIs) are common in children and generally self-limiting, yet often result in consultations to primary care. Frequent consultations divert resources from care for potentially more serious conditions and increase the opportunity for antibiotic overuse. Overuse of antibiotics is associated with adverse effects and antimicrobial resistance, and has been shown to influence how patients seek care in ensuing illness episodes. Methodology/Principal Findings We conducted a systematic review and meta-analysis to assess the effectiveness of interventions directed towards parents or caregivers which were designed to influence consulting and antibiotic use for respiratory tract infections (RTIs) in children in primary care. Main outcomes were parental consulting rate, parental knowledge, and proportion of children subsequently consuming antibiotics. Of 5,714 references, 23 studies (representing 20 interventions) met inclusion criteria. Materials designed to engage children in addition to parents were effective in modifying parental knowledge and behaviour, resulting in reductions in consulting rates ranging from 13 to 40%. Providing parents with delayed prescriptions significantly decreased reported antibiotic use (Risk Ratio (RR) 0.46 (0.40, 0.54); moreover, a delayed or no prescribing approach did not diminish parental satisfaction. Conclusions In order to be most effective, interventions to influence parental consulting and antibiotic use should: engage children, occur prior to an illness episode, employ delayed prescribing, and provide guidance on specific symptoms. These results support the wider implementation of interventions to reduce inappropriate antibiotic use in children.

Global prevalence of antibiotic resistance in paediatric urinary tract infections caused by Escherichia coli and association with routine use of antibiotics in primary care: systematic review and meta-analysis

Objectives To systematically review studies investigating the prevalence of antibiotic resistance in urinary tract infections caused by Escherichia coli in children and, when appropriate, to meta-analyse the relation between previous antibiotics prescribed in primary care and resistance. Design and data analysis Systematic review and meta-analysis. Pooled percentage prevalence of resistance to the most commonly used antibiotics in children in primary care, stratified by the OECD (Organisation for Economic Co-operation and Development) status of the study country. Random effects meta-analysis was used to quantify the association between previous exposure to antibiotics in primary care and resistance. Data sources Observational and experimental studies identified through Medline, Embase, Cochrane, and ISI Web of Knowledge databases, searched for articles published up to October 2015. Eligibility criteria for selecting studies Studies were eligible if they investigated and reported resistance in community acquired urinary tract infection in children and young people aged 0-17. Electronic searches with MeSH terms and text words identified 3115 papers. Two independent reviewers assessed study quality and performed data extraction. Results 58 observational studies investigated 77 783 E coli isolates in urine. In studies from OECD countries, the pooled prevalence of resistance was 53.4% (95% confidence interval 46.0% to 60.8%) for ampicillin, 23.6% (13.9% to 32.3%) for trimethoprim, 8.2% (7.9% to 9.6%) for co-amoxiclav, and 2.1% (0.8 to 4.4%) for ciprofloxacin; nitrofurantoin was the lowest at 1.3% (0.8% to 1.7%). Resistance in studies in countries outside the OECD was significantly higher: 79.8% (73.0% to 87.7%) for ampicillin, 60.3% (40.9% to 79.0%) for co-amoxiclav, 26.8% (11.1% to 43.0%) for ciprofloxacin, and 17.0% (9.8% to 24.2%) for nitrofurantoin. There was evidence that bacterial isolates from the urinary tract from individual children who had received previous prescriptions for antibiotics in primary care were more likely to be resistant to antibiotics, and this increased risk could persist for up to six months (odds ratio 13.23, 95% confidence interval 7.84 to 22.31). Conclusions Prevalence of resistance to commonly prescribed antibiotics in primary care in children with urinary tract infections caused by E coli is high, particularly in countries outside the OECD, where one possible explanation is the availability of antibiotics over the counter. This could render some antibiotics ineffective as first line treatments for urinary tract infection. Routine use of antibiotics in primary care contributes to antimicrobial resistance in children, which can persist for up to six months after treatment.

A systematic review of parent and clinician views and perceptions that influence prescribing decisions in relation to acute childhood infections in primary care

Abstract Objectives. To investigate the views of parents, clinicians, and children pertaining to prescribing decisions for acute childhood infection in primary care. Methods. A systematic review of qualitative studies. Meta-ethnographic methods were used, with data drawn from the primary studies in an interpretive analysis. Results. A total of 15 studies met the inclusion criteria. The literature was dominated by concerns about antibiotic over-prescription. Childrens views were not reported. Clinicians prescribed antibiotics when they felt pressured by parents or others (e.g. employers) to do so, when they believed there was a clear clinical indication, but also when they felt uncertain of clinical or social outcomes they prescribed “just in case”. Parents wanted antibiotics when they felt they would improve the current illness, and when they felt pressure from daycare providers or employers. Clinicians avoided antibiotics when they were concerned about adverse reactions or drug resistance, when certain they were not indicated, and when there was no perceived pressure from parents. Parents also wished to avoid adverse effects of antibiotics, and did not want antibiotics when they would not relieve current symptoms. Some parents preferred to avoid medication altogether. Within paediatric consultations, parents sought a medical evaluation and decision. Primary care clinicians want satisfied parents and short consultations. Conclusions. Antibiotic prescriptions for childhood infections in primary care often result from “just in case” prescribing. These findings suggest that interventions which reduce clinician uncertainty regarding social or clinical outcomes and provide strategies to meet parents’ needs within a short consultation are most likely to reduce antibiotic prescribing.

Predictors of suppurative complications for acute sore throat in primary care: prospective clinical cohort study

Objective To document whether elements of a structured history and examination predict adverse outcome of acute sore throat. Design Prospective clinical cohort. Setting Primary care. Participants 14 610 adults with acute sore throat (≤2 weeks’ duration). Main outcome measures Common suppurative complications (quinsy or peritonsillar abscess, otitis media, sinusitis, impetigo or cellulitis) and reconsultation with new or unresolving symptoms within one month. Results Complications were assessed reliably (inter-rater κ=0.95). 1.3% (177/13 445) of participants developed complications overall and 14.2% (1889/13 288) reconsulted with new or unresolving symptoms. Independent predictors of complications were severe tonsillar inflammation (documented among 13.0% (1652/12 717); odds ratio 1.92, 95% confidence interval 1.28 to 2.89) and severe earache (5% (667/13 323); 3.02, 1.91 to 4.76), but the model including both variables had modest prognostic utility (bootstrapped area under the receiver operator curve 0.61, 0.57 to 0.65), and 70% of complications (124/177) occurred when neither was present. Clinical prediction rules for bacterial infection (Centor criteria and FeverPAIN) also predicted complications, but predictive values were also poor and most complications occurred with low scores (67% (118/175) scoring ≤2 for Centor; 126/173 (73%) scoring ≤2 for FeverPAIN). Previous medical problems, sex, temperature, and muscle aches were independently but weakly associated with reconsultation with new or unresolving symptoms. Conclusion Important suppurative complications after an episode of acute sore throat in primary care are uncommon. History and examination and scores to predict bacterial infection cannot usefully identify those who will develop complications. Clinicians will need to rely on strategies such as safety netting or delayed prescription in managing the uncertainty and low risk of complications.

The science of clinical practice: disease diagnosis or patient prognosis? Evidence about "what is likely to happen" should shape clinical practice.

BackgroundDiagnosis is the traditional basis for decision-making in clinical practice. Evidence is often lacking about future benefits and harms of these decisions for patients diagnosed with and without disease. We propose that a model of clinical practice focused on patient prognosis and predicting the likelihood of future outcomes may be more useful.DiscussionDisease diagnosis can provide crucial information for clinical decisions that influence outcome in serious acute illness. However, the central role of diagnosis in clinical practice is challenged by evidence that it does not always benefit patients and that factors other than disease are important in determining patient outcome. The concept of disease as a dichotomous ‘yes’ or ‘no’ is challenged by the frequent use of diagnostic indicators with continuous distributions, such as blood sugar, which are better understood as contributing information about the probability of a patient’s future outcome. Moreover, many illnesses, such as chronic fatigue, cannot usefully be labelled from a disease-diagnosis perspective. In such cases, a prognostic model provides an alternative framework for clinical practice that extends beyond disease and diagnosis and incorporates a wide range of information to predict future patient outcomes and to guide decisions to improve them. Such information embraces non-disease factors and genetic and other biomarkers which influence outcome.SummaryPatient prognosis can provide the framework for modern clinical practice to integrate information from the expanding biological, social, and clinical database for more effective and efficient care.

Measuring the financial burden of acute cough in pre-school children: a cost of illness study

BackgroundContext: Acute cough is a very common symptom presentation among children in primary care and is usually due to respiratory infection, yet its cost is unknown. An estimate of the cost to healthcare providers and parents would aid budgetary decision-making, and provide an insight into the need for interventions to reduce the burden. Purpose: To estimate the cost per child per episode, and the annual population cost in the UK, of acute cough in pre-school children presenting to primary care.MethodsDesign: Incidence and prevalence-based cost-of-illness study from the perspectives of the UK NHS and of parents and caregivers. Setting: 11 general practices in Bristol, UK. Subjects: 121 children without known asthma aged 3 to 59 months presenting for the first time with an acute (≤ 28 days) cough.ResultsMean cost per episode to the NHS: £27.43 (95% CI: £24.38 – £30.49). Mean cost per episode to parents and carers: £14.77 (£4.90 – £24.65). Annual cost to the NHS in the UK: at least £31.5 m (95% CI: £28.0 m – £35.0 m).ConclusionThe cost burden on the healthcare provider of acute cough in pre-school children is substantial; the majority of this cost arises from consultations with general practitioners. Parents experience some personal cost through travel and expenditure on over-the-counter preparations, and may suffer significantly if loss of earnings is experienced. There is scope for evaluating interventions designed to reduce this burden.

Parents’ information needs, self-efficacy and influences on consulting for childhood respiratory tract infections: a qualitative study

BackgroundAcute respiratory tract infection (RTI) is the most common reason why parents consult primary care in the UK. Little is known about parents’ perceptions of what may help them to make an appropriate decision to consult when their child is ill and how to improve self-care.Using qualitative methods, this study aimed to explore parents’ views on support and information needs prior to consulting when children have RTIs with cough, and identify the triggers and barriers to consulting primary care.Methods7 focus groups and 30 semi-structured interviews were held with 60 parents (with children aged 5 months - 17 years) from a range of socio-economic backgrounds. Topics discussed were informed by the Health Belief Model, and explored parents’ concerns and beliefs about susceptibility and severity of RTIs, beliefs about the triggers and barriers to consulting, and information and support seeking behaviour undertaken before consulting primary care. Discussions were audio-recorded, transcribed and analysed using thematic methods.ResultsParents from all socio-economic backgrounds sought information from a wide range of sources about RTIs in children in order to identify which of their child’s symptoms should be of concern and trigger a visit to the doctor. The perception of threat to a child of RTI (with cough) was increased with more severe illness and by perceived susceptibility to illness of a particular child; whilst experience with other children increased parental efficacy to cope with childhood cough at home. Psychological models of health behaviour informed the understanding of cultural beliefs and attitudes that underpin health related behaviours.ConclusionA wide range of perceptions influence the likelihood that parents will seek help from primary care for a child with cough; these perceptions are similar across socio-economic groups. Parents’ experience, confidence and efficacy influence the likelihood of consulting primary care for their child’s RTI. Parents would value consistent advice from a trusted source that addresses common concerns and supports home care and decision making about help seeking.