Prevalence of, and risk factors for, antimicrobial resistance in paediatric urinary bacteria - a systematic review and meta-analysis

The problem

Bacterial resistance to antibiotics is placing a significant burden on both primary and secondary health care, with many first-line antibiotics now powerless against once easily treated infections. In primary care, this puts pressure on clinicians and nurses to prescribe stronger second or third-line antibiotics to patients, exposing bacteria to an array of further antibiotics to which they can acquire resistance. Children tend to have high primary care consultation rates and therefore receive high numbers of antibiotics compared to the adult population. Numerous studies have sought to better understand the prevalence of antibiotic resistance and the association between antibiotic use and resistance; however these are often limited to adult populations. Relatively little is known about the true burden of antibiotic resistance in children, and even less about the relationship between primary care antibiotic use and the isolation of resistant bacteria.

The approach

This review describes the epidemiology of bacterial resistance in Escherichia coli urinary isolates from children. Specific objectives were to investigate resistance patterns, stratified by Organisation for Economic Co-operation and Development (OECD) status. The relationship between antibiotic exposure and bacterial resistance was also explored. Studies were eligible if participants were aged 0-17 years presenting to primary care with acute illness and provided a urine sample. All urinary isolates were community-acquired. Medline and Embase searches identified 4146 papers. Two independent reviewers assessed eligibility and extracted data from 57 papers.Data regarding resistance to antibiotics was extracted. A random-effects meta-analysis was conducted exploring the association between antibiotic exposure on the isolation of a resistant urinary isolate, stratified by time of exposure.

Findings

Of the 57 included studies, 33 were from OECD countries and 24 from non-OECD countries. All studies were observational. In total, 72,988 children's E. coli urinary isolates were investigated; 68,766 from OECD countries and 4222 from non-OECD countries.OECD countries: pooled prevalence of resistance to antibiotics were: ampicillin 51.4% (95% confidence interval: 51-51.8%), co-amoxiclav 5.8% (5.6-6%), co-trimoxazole 23.5% (23.1-23.8%), trimethoprim 29.5% (28.8-30.1%), nitrofurantoin 0.8% (0.8-0.9%), ciprofloxacin 1.8% (1.7-1.9%) and ceftazidime 1.1% (1-1.3%).Non-OECD countries: pooled prevalence of resistance to antibiotics were: ampicillin 78.6% (76.9-80.2%), co-amoxiclav 54.8% (52.4-57.3%), co-trimoxazole 64.4% (62.7-66.1%), nitrofurantoin 9.9% (8.8-10.9%), ciprofloxacin 22.2% (20.5-23.9%) and ceftazidime 13.8% (11.9-15.7%).Temporal association: in six studies of children's urinary bacteria, the pooled odds ratio (OR) for resistance was 3.66 (95% CI: 1.65-8.10) for up to 1 month; and 2.18 (1.76-2.71) for up to 12 months post-antibiotic treatment.

Consequences

Resistance to many commonly prescribed antibiotics in children is high, particularly in non-OECD countries where antibiotics are available over-the-counter. There was strong evidence of an association between antibiotic prescribing and resistance, which can persist for at least 12 months. Surveillance systems could help clinicians minimise treatment failures due to bacterial resistance.

Credits

• Ashley Bryce, Queen Mary University of London, London, UK
• Alastair Hay, Queen Mary University of London, London, UK
• Ceire Costelloe