Faecal carriage of antibiotic resistant Escherichia coli in asymptomatic children and associations with primary care antibiotic prescribing:a systematic review and meta-analysis

Chloramphenicol resistance in faecal E. coli isolates from asymptomatic children, by OECD status. (DOCX 152 kb

Antibiotic prescribing in primary care and antimicrobial resistance in patients admitted to hospital with urinary tract infection: a controlled observational pilot study

There is growing evidence that primary care prescribed antibiotics lead to antibiotic resistance in bacteria causing minor infections or being carried by asymptomatic adults, but little research to date has investigated links between primary care prescribed antibiotics and resistance among more serious infections requiring hospital care. Knowledge of these effects is likely to have a major influence on public expectations for, and primary care use of, antibiotics. This study aimed to assess the feasibility of recruiting symptomatic adult patients admitted to hospital with urinary infections and to link primary and secondary data information to investigate the relationship between primary care prescribed antibiotics and antimicrobial resistance in these patients. A microbiology database search of in patients who had submitted a urine sample identified 740 patients who were potentially eligible to take part in the study. Of these, 262 patients did not meet the eligibility criteria, mainly due to use of a urinary catheter (40%). Two-hundred and forty three patients could not be recruited as the nurse was unable to visit the patients prior to discharge, as they were too unwell. Eighty patients provided complete information. Results indicate that there is evidence that prior antibiotic use is associated with resistant infections in hospital patients. A fully powered study, conducted using routinely collected data is proposed to fully clarify the precision of the association

Comparison of risk factors for, and prevalence of, antibiotic resistance in contaminating and pathogenic urinary Escherichia coli in children in primary care: prospective cohort study

Background All-cause antibiotic prescribing affects bowel flora antimicrobial susceptibility, and may increase risk of urinary autoinoculation with antibiotic-resistant microbes. However, little is known about relative prevalence of, or risk factors for, antimicrobial resistance among potentially pathogenic microbes thought to be contaminating and infecting urine. Methods Secondary analysis of 824 children under 5 years of age consulting in primary care for an acute illness and their Escherichia coli isolates cultured at ≥103 cfu/mL fromthe Diagnosis of Urinary Tract infection in Young children (DUTY) study. Multivariable logistic regression investigating risk factors for resistance to amoxicillin, co-amoxiclav, cefalexin, ciprofloxacin, trimethoprim, nitrofurantoin and cefpodoxime in microbes meeting the laboratory criteria for urinary tract infection: ‘pathogens’ (>105 cfu/mL, n=79) and ‘contaminants’ (103 to 105 cfu/mL, n=745). Results Forty-three percent of E. coli were resistant to at least one tested antibiotic, with resistance highest to amoxicillin (49.37% pathogenic versus 37.32% contaminant, P=0.04), trimethoprim (27.85% versus 16.52%, P=0.01) and co-amoxiclav (16.46% versus 21.48%, P=0.30). Multidrug resistance (to ≥3 antibiotic groups) was present in 17.07% of pathogens and 30.13% of contaminants (P=0.04). No isolates were resistant to nitrofurantoin. Recent (0–3months) exposure to antibiotics was associated with resistance in both pathogens (aOR: 1.10, 95% CI: 1.01–4.39) and contaminants (1.69, 1.09–2.67). Conclusions Prevalence of resistance (including multidrug) was high, but there was no consistent relationship between isolate pathogen/contamination status and resistance. Recent all-cause antibiotic prescribing increased the probability of antimicrobial resistance in both pathogenic and contaminating urinary E. coli in children in primary care.</p

Global prevalence of antibiotic resistance in paediatric urinary tract infections caused by <i>Escherichia coli</i> and association with routine use of antibiotics in primary care:a 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

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

Objective To estimate the cost to the NHS and to parents and carers of treating febrile preschool children with paracetamol, ibuprofen, or both, and to compare these costs with the benefits of each treatment regimen

Pilot study of a randomised trial of a guided e-learning health promotion intervention for managers based on management standards for the improvement of employee well-being and reduction of sickness absence: the GEM (Guided E-learning for Managers) study

Background: Psychosocial work environments influence employee well-being. There is a need for an evaluation of organisational-level interventions to modify psychosocial working conditions and hence employee well-being. Objective: To test the acceptability of the trial and the intervention, the feasibility of recruitment and adherence to and likely effectiveness of the intervention within separate clusters of an organisation. Design: Mixed methods: pilot cluster randomised controlled trial and qualitative study (in-depth interviews, focus group and observation). Participants: Employees and managers of a NHS trust. Inclusion criteria were the availability of sickness absence data and work internet access. Employees on long-term sick leave and short-term contracts and those with a notified pregnancy were excluded. Intervention: E-learning program for managers based on management standards over 10 weeks, guided by a facilitator and accompanied by face-to-face meetings. Three clusters were randomly allocated to receive the guided e-learning intervention; a fourth cluster acted as a control. Main outcome measures: Recruitment and participation of employees and managers; acceptability of the intervention and trial; employee subjective well-being using the Warwick–Edinburgh Mental Wellbeing Scale (WEMWBS); and feasibility of collecting sickness absence data. Results: In total, 424 employees out of 649 approached were recruited and 41 managers out of 49 were recruited from the three intervention clusters. Of those consenting, 350 [83%, 95% confidence interval (CI) 79% to 86%] employees completed the baseline assessment and 291 (69%, 95% CI 64% to 73%) completed the follow-up questionnaires. Sickness absence data were available from human resources for 393 (93%, 95% CI 90% to 95%) consenting employees. In total, 21 managers adhered to the intervention, completing at least three of the six modules. WEMWBS scores fell slightly in all groups, from 50.4 to 49.0 in the control group and from 51.0 to 49.9 in the intervention group. The overall intervention effect was 0.5 (95% CI –3.2 to 4.2). The fall in WEMWBS score was significantly less among employees whose managers adhered to the intervention than among those employees whose managers did not (–0.7 vs. 1.6, with an adjusted difference of 1.6, 95% CI 0.1 to 3.2). The intervention and trial were acceptable to managers, although our study raises questions about the widely used concept of ‘acceptability’. Managers reported insufficient time to engage with the intervention and lack of senior management ‘buy-in’. It was thought that the intervention needed better integration into organisational processes and practice. Conclusions: The mixed-methods approach proved valuable in illuminating reasons for the trial findings, for unpacking processes of implementation and for understanding the influence of study context. We conclude from the results of our pilot study that further mixed-methods research evaluating the intervention and study design is needed. We found that it is feasible to carry out an economic evaluation of the intervention. We plan a further mixed-methods study to re-evaluate the intervention boosted with additional elements to encourage manager engagement and behaviour change in private and public sector organisations with greater organisational commitment

Validating a prediction tool to determine the risk of nosocomial multidrug-resistant Gram-negative bacilli infection in critically ill patients: A retrospective case–control study

BACKGROUND:The Singapore GSDCS score was developed to enable clinicians predict the risk of nosocomial multidrug-resistant Gram-negative bacilli (RGNB) infection in critically ill patients. We aimed to validate this score in a UK setting. METHOD:A retrospective case-control study was conducted including patients who stayed for more than 24h in intensive care units (ICUs) across two tertiary National Health Service hospitals in London, UK (April 2011-April 2016). Cases with RGNB and controls with sensitive Gram-negative bacilli (SGNB) infection were identified. RESULTS:The derived GSDCS score was calculated from when there was a step change in antimicrobial therapy in response to clinical suspicion of infection as follows: prior Gram-negative organism, Surgery, Dialysis with end-stage renal disease, prior Carbapenem use and intensive care Stay of more than 5 days. A total of 110 patients with RGNB infection (cases) were matched 1:1 to 110 geotemporally chosen patients with SGNB infection (controls). The discriminatory ability of the prediction tool by receiver operating characteristic curve analysis in our validation cohort was 0.75 (95% confidence interval 0.65-0.81), which is comparable with the area under the curve of the derivation cohort (0.77). The GSDCS score differentiated between low- (0-1.3), medium- (1.4-2.3) and high-risk (2.4-4.3) patients for RGNB infection (P<0.001) in a UK setting. CONCLUSION:A simple bedside clinical prediction tool may be used to identify and differentiate patients at low, medium and high risk of RGNB infection prior to initiation of prompt empirical antimicrobial therapy in the intensive care setting