Antibiotic Resistance Continues to be a Problem in Children

Lara C. Pullen, PhD

March 23, 2016

As many as half of the children in economically developed countries who have a urinary tract infection caused by Escherichia coli have infections that are resistant to antibiotics commonly prescribed in primary care. Even more concerning is the fact that the antimicrobial resistance in children appears to persist for up to 6 months after treatment.

In addition, the percentage of antibiotic-resistant isolates jumps as high as 80% in children who live outside of the Organisation for Economic Co-operation and Development (OECD). Such non-OECD countries include Brazil, China, and Malaysia.

Ashley Bryce, from the University of Bristol in the United Kingdom, and colleagues published their systematic review and meta-analysis online March 15 in the BMJ. The authors identified 58 observational studies from OECD and non-OECD countries and used their results to calculate the rates of bacterial resistance in E coli isolates from children with urinary tract infection.

In OECD countries, the pooled prevalence of resistance was 53.4% (95% confidence interval [CI], 46.0% - 60.8%) for ampicillin, 23.6% (95% CI, 13.9% - 32.3%) for trimethoprim, 8.2% (95% CI, 7.9% - 9.6%) for co-amoxiclav, and 2.1% (95% CI, 0.8% - 4.4%) for ciprofloxacin.

Non-OECD countries had much higher rates of resistance, at 79.8% (95% CI, 73.0% - 87.7%) for ampicillin, 60.3% (95% CI, 40.9% - 79.0%) for co-amoxiclav, 26.8% (95% CI, 11.1% - 43.0%) for ciprofloxacin, and 17.0% (95% CI, 9.8% - 24.2%) for nitrofurantoin.

The results are similar to those published in a 2010 meta-analysis that examined the association between exposure to antibiotics in the previous 6 months and the presence of resistant urinary isolates. The current study expands on these data, however, by characterizing global patterns of resistance.

"To our knowledge, this is the first systematic review and meta-analysis to explore and report global evidence regarding the prevalence of bacterial resistance in children's urinary tract infection and associations with the routine use of antibiotics in primary care. [The World Health Organization] recently published their 'global action plan' on antimicrobial resistance, which described data relating to the prevalence of resistance, including geographical patterns, as a key gap in our current knowledge, which this systematic review in part fills," the authors write.

In most countries, children who present to primary care with a suspected urinary tract infection are treated empirically with an antibiotic. Because antibiotics are available over the counter in many non-OECD countries, however, antibiotics are used differently in different countries. This makes it difficult to quantify antibiotic exposure in non-OECD countries.

Only five studies documented an association between previous antibiotic exposure and resistance that occurred in overlapping periods. Data from these studies indicate that antibiotic resistance can persist for 6 months after exposure to antibiotics.

Although the timing of exposure to antibiotics was difficult to quantify, the authors had more confidence in their antimicrobial resistance data, which were consistent with other analyses of US and European Union rates of antibiotic resistance.

Policy Implications

"Our findings detail global high level resistance to some of the most commonly prescribed antibiotics for children [in] primary care, which could result in several drugs becoming ineffective first line treatments in many countries," the authors emphasize.

The persistence of antibiotic resistance for up to 6 months is particularly troubling, and the authors call for more studies to include incident antibiotic use so that data on the persistence of resistance can continue to be documented.

In an accompanying editorial, Grant Russell, MD, PhD, from Monash University in Melbourne, Australia, called for global policy changes, "Bryce and colleagues' systematic review joins a host of recent studies, reports, and calls to action on this issue. Each adds evidence to justify change in how we protect a precious global resource. While I have no doubt that clinical practice guidelines will quickly be able to accommodate the findings, I am less confident that there is the will and commitment to deal with what the [World Health Organization] has called 'the post-antibiotic era.' "

The authors and Dr Russell have disclosed no relevant financial relationships.

BMJ. Published online March 15, 2016. Article full text, Editorial full text

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