Wednesday March 16 2016
Ampicillin is used to treat urinary tract infections in children
"Antibiotics used to treat common infections in children could soon be rendered useless," the Daily Mail reports.
A major review of existing data found worryingly high levels of resistance to widely used antibiotics such as ampicillin, which is used to treat urinary tract infections (UTIs) in children. Researchers specifically looked at UTIs caused by E. coli, a very common bacteria.
In the UK and other developed countries, around a quarter to half of E. coli infections were resistant to the common antibiotics trimethoprim and ampicillin (or amoxicillin), though resistance was lower against other drugs. Researchers say prescribing guidelines need to be updated to take account of their findings.
The researchers also found bacteria carried by individual children were more likely to be antibiotic resistant for up to six months after the child had taken antibiotics.
An editorial published alongside the study suggests doctors should avoid prescribing a child the same antibiotic more than once in six months.
The study found antibiotic resistance was much more common in less developed countries, where antibiotics are more often available over the counter, rather than by prescription.
This research is a stark reminder of the importance of using antibiotics only when necessary, and to take the full course when they are used, to avoid giving bacteria the chance to develop resistance to a drug.
Read more about how to combat antibiotic resistance.
Where did the story come from?
The study was carried out by researchers from the University of Bristol, University Hospital of Wales, and Imperial College London.
It was funded by the National Institute of Health Research.
The study was published in the peer-reviewed British Medical Journal (BMJ) on an open access basis, so it is free to read online.
The Guardian seems to place the blame on family doctors, saying the researchers "blame GPs for prescribing antibiotics to children too often".
However, the study authors pointed out that children with urine infections are prone to serious complications and "require prompt appropriate treatment".
They point to the unregulated use of antibiotics without prescription as one reason for higher antibiotic resistance in less developed countries.
The Daily Telegraph, confusingly, reported: "Half of children are now resistant to some of the most common antibiotics". It's not children that are resistant, but bacteria.
This is an important distinction – drug resistance changes over time, and antibiotics that don't work for a child with one infection may work for another.
What kind of research was this?
Researchers carried out a systematic review of observational studies from all over the world, which calculated the proportion of antibiotic-resistant E. coli urinary infections in children under 18.
They also carried out a meta-analysis of studies that calculated how likely children were to carry antibiotic-resistant bacteria in their urine after being prescribed antibiotics.
Systematic reviews and meta-analyses are good ways to summarise and pool information about a topic. However, they're only as good as the studies they include.
What did the research involve?
Researchers searched for studies that measured antibiotic resistance to a selection of commonly used antibiotics among E. coli urine infections in children.
They divided the studies into those carried out in Organisation for Economic Co-operation and Development countries (OECD) – countries such as the UK and France are regarded as developed – and non-OECD (less developed) countries.
They then pooled the data to come up with estimates of what proportion of E. coli were resistant to different antibiotics.
The data collected was used to see if children were more likely to harbour antibiotic-resistant E. coli if they'd been prescribed antibiotics in the previous six months.
The researchers included 58 studies, of which 33 were from developed countries. Only five studies, all from developed countries, included information about whether children had previously been prescribed antibiotics.
Some, but not all, of the studies included information about how the urine samples were collected and tested, or which guidelines had been used. The researchers looked to see if these factors affected the results, or whether the results were affected by the children's age or sex.
What were the basic results?
More than half the infections were resistant to ampicillin, one of the most commonly used antibiotics for urinary tract infections worldwide.
Resistance to ampicillin – or its derivative, amoxicillin – was found in 53.4% of cases in developed countries and 79.8% of cases in less developed countries.
Ampicillin is one of the drugs recommended by NICE for use in childhood urine infections in the UK. Another recommended drug, trimethoprim, was ineffective in 23.6% of cases in developed countries.
Other commonly used antibiotics with resistance rates above 20% – the recommended level above which a drug should not be routinely used – included co-trimoxazole, and co-amoxiclav in less developed countries.
None of the routinely used antibiotics in less developed countries had resistance rates below 20%. The drug with lowest resistance in developed countries was nitrofurantoin (1.3%), which was only recorded in one study from less developed countries.
Children were more than eight times more likely to have bacteria in their urine resistant to an antibiotic if they'd been prescribed that antibiotic one month earlier (odds ratio 8.38, 95% confidence interval 2.84 to 24.77).
Because studies looked at overlapping time periods, it wasn't possible to do an overall summary of all time periods up to six months.
But a study that measured antibiotic-resistant bacteria in children who'd been prescribed an antibiotic at regular intervals showed it declined over time, with no increased chance of antibiotic resistance a year or more after taking a drug.
How did the researchers interpret the results?
The researchers said their findings show that guidelines need to be updated: "Our review suggests ampicillin, co-trimoxazole and trimethoprim are no longer suitable first line options for urinary tract infection in many OECD countries."
They suggest that nitrofurantoin "might be the most appropriate first line treatment for lower urinary tract infection" and suggest that doctors should take a child's previous antibiotic use into account when choosing antibiotics for further infections.
They said antibiotic resistance in less developed countries might be tackled by better primary care facilities, better access to medical help, and regulation of the supply of antibiotics.
This is an important study that may mean doctors need to change the way they treat one of the most common childhood illnesses.
Because urine infections can be painful and can damage the kidneys in young children, it's important they are treated quickly and effectively.
Current guidelines for doctors, which were published nine years ago, say children over three months of age with urine infections should be treated for three days with an antibiotic "directed by locally developed guidance", which might include trimethoprim, nitrofurantoin, cephalosporin or amoxicillin.
Only if the antibiotic does not work does the guidance recommend sending a urine sample for analysis. Infants with a suspected urine infection below three months of age require immediate referral and investigation.
There are some uncertainties about the study results. For example, there are too few studies looking at bacteria resistance to antibiotics over time to be sure about how long resistance lasts. As these are observational studies, we don't know whether other factors might have influenced the results.
Also, the studies covered age ranges from infants up to young people aged 17 years. As highlighted in the accompanying editorial, there is quite a difference between a young adult presenting to the doctor with clear symptoms of a urine infection and a young child with more non-specific symptoms, such as a temperature and abdominal pain. There may be more uncertainty about diagnosis in younger children.
Nevertheless, the review is large and the overall results seem compelling enough that it should be taken seriously. The results suggest doctors should use a different antibiotic as a first choice, and also check which antibiotics the child has taken in the previous six months and avoid using those.
The study highlights the growing importance of resistance to antibiotics by bacteria. Everyone has a part to play in preventing this spread. Bacteria become resistant because they mutate and adapt, so certain antibiotics no longer kill them.
We need to avoid using antibiotics for illnesses that don't need them – for example, colds and flu, which are not caused by bacteria – and use them properly when they are necessary.
That means finishing a course of antibiotics, even if you feel better before they're finished. Leaving a course unfinished means some bacteria survive and can mutate and develop resistance.
Authorities such as the National Institute for Health and Care Excellence (NICE) will need to take account of this research when updating guidelines on how antibiotics should be used to treat urine infections in children.