Hannah Thornton

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.

Overtreatment of COPD with Inhaled Corticosteroids - Implications for Safety and Costs: Cross-Sectional Observational Study

Introduction Combined inhaled long-acting beta-agonists and corticosteroids (LABA+ICS) are costly. They are recommended in severe or very severe chronic obstructive pulmonary disease (COPD). They should not be prescribed in mild or moderate disease. In COPD ICS are associated with side-effects including risk of pneumonia. We quantified appropriateness of prescribing and examined the risks and costs associated with overuse. Methods Data were extracted from the electronic and paper records of 41 London general practices (population 310,775) including spirometry, medications and exacerbations. We classified severity, assessed appropriateness of prescribing using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for 2009, and performed a sensitivity analysis using the broader recommendations of the 2011 revision. Results 3537 patients had a diagnosis of COPD. Spirometry was recorded for 2458(69%). 709(29%) did not meet GOLD criteria. 1749(49%) with confirmed COPD were analysed: 8.6% under-treated, 38% over-treated. Over-prescription of ICS in GOLD stage I or II (n=403, 38%) and in GOLD III or IV without exacerbations (n=231, 33.6%) was common. An estimated 12 cases (95%CI 7-19) annually of serious pneumonia were likely among 897 inappropriately treated. 535 cases of overtreatment involved LABA+ICS with a mean per patient cost of £553.56/year (€650.03). Using the broader indications for ICS in the 2011 revised GOLD guideline 25% were still classified as over-treated. The estimated risk of 15 cases of pneumonia (95%CI 8-22) in 1074 patients currently receiving ICS would rise by 20% to 18 (95%CI 9.8-26.7) in 1305 patients prescribed ICS if all with GOLD grade 3 and 4 received LABA+ICS. Conclusion Over-prescription of ICS in confirmed COPD was widespread with considerable potential for harm. In COPD where treatment is often escalated in the hope of easing the burden of disease clinicians should consider both the risks and benefits of treatment and the costs where the benefits are unproven.

The TARGET cohort study protocol: a prospective primary care cohort study to derive and validate a clinical prediction rule to improve the targeting of antibiotics in children with respiratory tract illnesses

BackgroundChildren with respiratory tract infections are the single most frequent patient group to make use of primary care health care resources. The use of antibiotics remains highly prevalent in young children, but can lead to antimicrobial resistance as well as reinforcing the idea that parents should re-consult for similar symptoms. One of the main drivers of indiscriminate antimicrobial use is the lack of evidence for, and therefore uncertainty regarding, which children are at risk of poor outcome. This paper describes the protocol for the TARGET cohort study, which aims to derive and validate a clinical prediction rule to identify children presenting to primary care with respiratory tract infections who are at risk of hospitalisation.Methods/designThe TARGET cohort study is a large, multicentre prospective observational study aiming to recruit 8,300 children aged ≥3 months and <16 years presenting to primary care with a cough and respiratory tract infection symptoms from 4 study centres (Bristol, London, Oxford and Southampton). Following informed consent, symptoms, signs and demographics will be measured. In around a quarter of children from the Bristol centre, a single sweep, dual bacterial-viral throat swab will be taken and parents asked to complete a symptom diary until the child is completely well or for 28 days, whichever is sooner. A review of medical notes including clinical history, re-consultation and hospitalisations will be undertaken. Multivariable logistic regression will be used to identify the independent clinical predictors of hospitalisation as well as the prognostic significance of upper respiratory tract microbes. The clinical prediction rule will be internally validated using various methods including bootstrapping.DiscussionThe clinical prediction rule for hospitalisation has the potential to help identify a small group of children for hospitalisation and a much larger group where hospitalisation is very unlikely and antibiotic prescribing would be less warranted. This study will also be the largest natural history study to date of children presenting to primary care with acute cough and respiratory tract infections, and will provide important information on symptom duration, re-consultations and the microbiology of the upper respiratory tract.

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

Summary Background Antimicrobial resistance is a serious threat to public health, with most antibiotics prescribed in primary care. General practitioners (GPs) report defensive antibiotic prescribing to mitigate perceived risk of future hospital admission in children with respiratory tract infections. We developed a clinical rule aimed to reduce clinical uncertainty by stratifying risk of future hospital admission. Methods 8394 children aged between 3 months and 16 years presenting with acute cough (for ≤28 days) and respiratory tract infection were recruited to a prognostic cohort study from 247 general practitioner practices in England. Exposure variables included demographic characteristics, parent-reported symptoms, and physical examination signs. The outcome was hospital admission for respiratory tract infection within 30 days, collected using a structured, blinded review of medical records. Findings 8394 (100%) children were included in the analysis, with 78 (0·9%, 95% CI 0·7%–1·2%) admitted to hospital: 15 (19%) were admitted on the day of recruitment (day 1), 33 (42%) on days 2–7; and 30 (39%) on days 8–30. Seven characteristics were independently associated (p<0·01) with hospital admission: age <2 years, current asthma, illness duration of 3 days or less, parent-reported moderate or severe vomiting in the previous 24 h, parent-reported severe fever in the previous 24 h or a body temperature of 37·8°C or more at presentation, clinician-reported intercostal or subcostal recession, and clinician-reported wheeze on auscultation. The area under the receiver operating characteristic (AUROC) curve for the coefficient-based clinical rule was 0·82 (95% CI 0·77–0·87, bootstrap validated 0·81). Assigning one point per characteristic, a points-based clinical rule consisting of short illness, temperature, age, recession, wheeze, asthma, and vomiting (mnemonic STARWAVe; AUROC 0·81, 0·76–0·85) distinguished three hospital admission risk strata: very low (0·3%, 0·2–0·4%) with 1 point or less, normal (1·5%, 1·0–1·9%) with 2 or 3 points, and high (11·8%, 7·3–16·2%) with 4 points or more. Interpretation Clinical 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. Funding National Institute for Health Research (NIHR).

Clinical presentation and microbiological diagnosis in paediatric respiratory tract infection: a systematic review

BACKGROUND Antibiotic prescribing decisions for respiratory tract infection (RTI) in primary care could be improved if clinicians could target bacterial infections. However, there are currently no evidence-based diagnostic rules to identify microbial aetiology in children presenting with acute RTIs. AIM To analyse evidence of associations between clinical symptoms or signs and detection of microbes from the upper respiratory tract (URT) of children with acute cough. DESIGN AND SETTING Systematic review and meta-analysis. METHOD A literature search identified articles reporting relationships between individual symptoms and/or signs, and microbes detected from URT samples. Associations between pathogens and symptoms or signs were summarised, and meta-analysis conducted where possible. RESULTS There were 9984 articles identified, of which 28 met inclusion criteria. Studies identified 30 symptoms and 41 signs for 23 microbes, yielding 1704 potential associations, of which only 226 (13%) have presently been investigated. Of these, relevant statistical analyses were presented for 175 associations, of which 25% were significant. Meta-analysis demonstrated significant relationships between respiratory syncytial virus (RSV) detection and chest retractions (pooled odds ratio [OR] 1.9, 95% confidence interval [CI] = 1.6 to 2.3), wheeze (pooled OR 1.7, 95% CI = 1.5 to 2.0), and crepitations/crackles (pooled OR 1.7, 95% CI = 1.3 to 2.2). CONCLUSIONS There was an absence of evidence for URT pathogens other than RSV. The meta-analysis identified clinical signs associated with RSV detection, suggesting clinical presentation may offer some, albeit poor, diagnostic value. Further research is urgently needed to establish the value of symptoms and signs in determining microbiological aetiology and improve targeting of antibiotics in primary care.

Hospital readmissions for COPD: A retrospective longitudinal study

Prevention of chronic obstructive pulmonary disease hospital readmissions is an international priority aimed to slow disease progression and limit costs. Evidence of the risk of readmission and of interventions that might prevent it is lacking. We aimed to determine readmission risk for chronic obstructive pulmonary disease, factors influencing that risk, and variation in readmission risk between hospitals across 7.5 million people in London. This retrospective longitudinal observational study included all chronic obstructive pulmonary disease admissions to any hospital in the United Kingdom among patients registered at London general practices who had emergency National Health Service chronic obstructive pulmonary disease hospital admissions between April 2006 and March 2010. Influence of patient characteristics, geographical deprivation score, length of stay, day of week of admission or of discharge, and admitting hospital, were assessed using multiple logistic regression. 38,894 chronic obstructive pulmonary disease admissions of 20,932 patients aged ≥ 45 years registered with London general practices were recorded. 6295 patients (32.2%) had at least one chronic obstructive pulmonary disease readmission within 1 year. 1993 patients (10.2%) were readmitted within 30 days and 3471 patients (17.8%) were readmitted within 90 days. Age and patient geographical deprivation score were very weak predictors of readmission. Rates of chronic obstructive pulmonary disease readmissions within 30 days and within 90 days did not vary among the majority of hospitals. The finding of lower chronic obstructive pulmonary disease readmission rates than was previously estimated and the limited variation in these rates between hospitals suggests that the opportunity to reduce chronic obstructive pulmonary disease readmission risk is small.Chronic lung disease: Lower risk of readmission for London-based patientsA managed reduction of hospital readmissions for London-based chronic lung disease patients may not be needed. Preventing hospital readmissions for patients with chronic obstructive pulmonary disease (COPD) is a key priority to improve patient care and limit costs. However, few data are available to determine and ultimately reduce the risk of readmission. Timothy Harries at King’s College, London, and co-workers conducted a longitudinal study incorporating all COPD admissions into UK hospitals for 20,932 patients registered at London general practitioners between 2006 and 2010. They found that 32% of patients were readmitted within a year, 17.8% within 90 days and 10% within 30 days. Neither age nor geographical deprivation were useful predictors of readmission. These represent lower than estimated levels of readmission, suggesting there may be fewer opportunities to reduce the risk of readmission further.

Length of stay of COPD hospital admissions between 2006 and 2010: a retrospective longitudinal study

Background Hospitalizations for COPD are associated with poor patient prognosis. Length of stay (LOS) of COPD admissions in a large urban area and patient and hospital factors associated with it are described. Methods Retrospective longitudinal study. All COPD patients registered with London general practitioners and admitted as an emergency with COPD (2006–2010), not having been admitted with COPD in the preceding 12 months were included. Association of patient and hospital characteristics with mean LOS of COPD admissions was assessed. Association between hospital and LOS was determined by negative binomial regression. Results The total number of admissions was 38,504, from 22,462 patients. The mean LOS for first admissions fell by 0.8 days (95% confidence interval [CI]: 0.7–1.5) from 8.2 to 7.0 days between 2006 and 2010. Seventy-nine percent of first admissions were ≤10 days, with a mean LOS of 3.7 days (2009–2010). The mean LOS of successive COPD admissions of the same patients was the same or less throughout the study period. The interval between successive admissions fell from a mean of 357 days between the first and second admission to a mean of 19 days after eight admissions. Age accounted for 2.3% of the variance in LOS. Socioeconomic deprivation did not predict LOS. Fewer discharges happened at the weekend (1,893/day) than on weekdays (5,218/day). The mean LOS varied between hospitals, from 4.9 days (95% CI: 3.8–5.9) to 9.5 days (95% CI: 8.6–10.3) when adjusting for clustering, age, sex, and socioeconomic deprivation. Conclusion The fall in LOS of the first COPD admission between 2006 and 2010 reflects international trends. The stability of LOS in successive admissions suggests that increasing severity of disease does not affect recovery time from an exacerbation. Variations between hospitals of nearly 5 days in LOS for COPD admissions suggests that significant improvements in patient outcomes and in savings in health care utilization could be made in hospitals with longer LOS.

Emergency Admissions for COPD in an Urban Population: The Role of Population and Primary Care Factors.

Abstract COPD is a major cause of emergency admissions worldwide. In many countries the majority of COPD care is provided by primary care teams. This study examined variation between primary care teams in rates of COPD admission and assessed the role of prevalence, deprivation, practice performance, and general practitioner (GP) and nurse supply on risk of COPD admission. Retrospective observational study of National Health Service admissions for COPD of patients registered with London general practices over four years (2006–2009). We sought associations using negative binomial regression between COPD admissions and population factors, practice organization and practice performance. Trends in rates of COPD admissions across London were stable between 2006 and 2009. COPD admission rates varied substantially between practices (2006/7: median 13.68/10,000 population (IQR 7.83–22.70)), with almost a 3-fold difference across the interquartile range each year. Practice characteristics varied to a similar extent. Variation in practice COPD admission rates was associated with diagnosed prevalence of COPD (Rate Ratio 2.06, 95% CI 1.84–2.3) and increasing levels of deprivation (RR 1.01, 1.006–1.01). Other practice characteristics, including GP and nurse supply, and practice performance scores were not predictive of practice level COPD admission rates, when controlling for COPD prevalence and socio-economic status. Main predictors of variation in rates of COPD admissions were prevalence of diagnosed COPD and socioeconomic status. The absence of evidence that variation in primary care services for COPD was associated with rates of COPD admission emphasizes the importance of primary prevention of COPD if COPD admission rates are to fall.

Throat swabs in children with respiratory tract infection: associations with clinical presentation, and potential targets for point-of-care testing

Abstract Background and objectives. Diagnostic uncertainty over respiratory tract infections (RTIs) in primary care contributes to over-prescribing of antibiotics and drives antibiotic resistance. If symptoms and signs predict respiratory tract microbiology, they could help clinicians target antibiotics to bacterial infection. This study aimed to determine relationships between symptoms and signs in children presenting to primary care and microbes from throat swabs. Methods. Cross-sectional study of children ≥3 months to <16 years presenting with acute cough and RTI, with subset follow-up. Associations and area under receiver operating curve (AUROC) statistics sought between clinical presentation and baseline microbe detection. Microbe prevalence compared between baseline (symptomatic) and follow-up (asymptomatic) visits. Results. At baseline, ≥1 bacteria was detected in 1257/2113 (59.5%) children and ≥1 virus in 894/2127 (42%) children. Clinical presentation was not associated with detection of ≥1 bacteria [AUROC 0.54 (95% CI 0.52–0.56)] or ≥1 virus [0.64 (95% CI 0.61–0.66)]. Individually, only respiratory syncytial virus (RSV) was associated with clinical presentation [AUROC 0.80 (0.77–0.84)]. Prevalence fell between baseline and follow-up; more so in viruses (68% versus 26%, P < 0.001) than bacteria (56% versus 40%, P = 0.01); greatest reductions seen in RSV, influenza B and Haemophilus influenzae. Conclusion. Findings demonstrate that clinical presentation cannot distinguish the presence of bacteria or viruses in the upper respiratory tract. However, individual and overall microbe prevalence was greater when children were unwell than when well, providing some evidence that upper respiratory tract microbes may be the cause or consequence of the illness. If causal, selective microbial point-of-care testing could be beneficial.

Post-consultation illness trajectories in children with acute cough and respiratory tract infection: prospective cohort study

Abstract Background Little is known about respiratory tract infection (RTI) severity in children following consultation. Objectives To investigate post-consultation symptom trajectories in children with acute cough and RTI and whether baseline characteristics predict trajectory group. Methods Prospective cohort study of 2296 children (3 months–16 years) whose parents were invited to report cough severity and duration using a 7-point Likert scale. Longitudinal latent class analysis (LLCA) was used to identify post-consultation symptom trajectories in the first 15 days, and multinomial models to predict class membership. Results Complete data were available for 1408 children (61%). The best LLCA model identified five post-consultation symptom trajectory groups: ‘very rapid recovery’ (28.5%), ‘rapid recovery’ (37.7%), ‘intermediate recovery’ (18.2%), ‘persistent symptoms’ (9.5%) and ‘initial deterioration with persistent symptoms’ (6.0%). Compared with very rapid recovery, parent-reported severe cough in the 24 hours prior to consultation increased the likelihood of rapid recovery (OR 1.79 [95% CI 1.23, 2.60]), intermediate recovery (OR 2.13 [1.38, 3.30] and initial deterioration with persistent symptoms (OR 2.29 [1.26, 4.16]). Initial deterioration was also associated with ‘severe barking cough’ (OR 3.64 [1.50, 8.82]), ‘severely reduced energy in the 24 hours prior to consultation’ (OR 3.80 [1.62, 8.87] and higher parent-assessed illness severity at consultation (OR 2.21 [1.17, 4.18]). Conclusion We identified five distinct symptom trajectory groups showing the majority of children improved post-consultation, with only one group experiencing illness deterioration. The few characteristics associated with group membership did not fall into a pattern that seemed clinically useful.