Does locally relevant, real-time infection epidemiological data improve clinician management and antimicrobial prescribing in primary care? A systematic review.

Purpose: Antimicrobial resistance is a significant threat to public health. Diagnostic uncertainty is a key driver of antimicrobial prescribing. We sought to determine whether locally relevant, real-time syndromic or microbiological infection epidemiology can improve prescribing by reducing diagnostic uncertainty. Methods: Eligible studies investigated effects on primary care prescribing for common infections in Organisation For Economic Co-Operation And Development countries. We searched Medline, Embase, Cumulative index to nursing and allied health literature, Web of Science, grey literature sources, thesis databases and trial registries. Results: We identified 9548 reports, of which 17 were eligible, reporting 12 studies, of which 3 reported relevant outcomes. The first (observational) showed antibacterial prescribing for upper respiratory infections reduced from 26.4% to 8.6% (P = 0.01). The second (observational) showed antibacterial prescribing reduced during influenza pandemic compared with seasonal influenza periods [odds ratio (OR) 0.72 (95% CI, 0.68 to 0.77), P < 0.001], while antiviral prescribing increased [OR 6.43 (95% CI, 5.02 to 8.25), P < 0.001]. The likelihood of prescribing also decreased as the number of infection cases a physician saw increased in the previous week [OR 0.57 (95% CI, 0.51 to 0.63), P < 0.001 for ≥12 versus ≤1 patient). The third (randomized-controlled trial) showed an absolute reduction in antibacterial prescribing of 5.1% during a period of moderate influenza activity (P < 0.05). We did not find measures of diagnostic certainty, harms or costs. Conclusion: There is promising evidence that epidemiological syndromic and microbiological data can reduce primary care antimicrobial prescribing. Future research should use randomized designs of behaviourally informed interventions, investigate costs and harms, and establish mechanisms of behaviour change. PROSPERO registration: CRD42016038871.

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 from the 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 (0-3 months) 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.

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

BACKGROUND: The faecal reservoir provides optimal conditions for the transmission of resistance genes within and between bacterial species. As key transmitters of infection within communities, children are likely important contributors to endemic community resistance. We sought to determine the prevalence of antibiotic-resistant faecal Escherichia coli from asymptomatic children aged between 0 and 17 years worldwide, and investigate the impact of routinely prescribed primary care antibiotics to that resistance. METHODS: A systematic search of Medline, Embase, Cochrane and Web of Knowledge databases from 1940 to 2015. Pooled resistance prevalence for common primary care antibiotics, stratified by study country OECD status. Random-effects meta-analysis to explore the association between antibiotic exposure and resistance. RESULTS: Thirty-four studies were included. In OECD countries, the pooled resistance prevalence to tetracycline was 37.7 % (95 % CI: 25.9-49.7 %); ampicillin 37.6 % (24.9-54.3 %); and trimethoprim 28.6 % (2.2-71.0 %). Resistance in non-OECD countries was uniformly higher: tetracycline 80.0 % (59.7-95.3 %); ampicillin 67.2 % (45.8-84.9 %); and trimethoprim 81.3 % (40.4-100 %). We found evidence of an association between primary care prescribed antibiotics and resistance lasting for up to 3 months post-prescribing (pooled OR: 1.65, 1.36-2.0). CONCLUSIONS: Resistance to many primary care prescribed antibiotics is common among faecal E. coli carried by asymptomatic children, with higher resistance rates in non-OECD countries. Despite tetracycline being contra-indicated in children, tetracycline resistance rates were high suggesting children could be important recipients and transmitters of resistant bacteria, or that use of other antibiotics is leading to tetracycline resistance via inter-bacteria resistance transmission.

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.