“I think part of the problem with childhood antibiotic resistance is it's invisible,” she said.
But while resistance to Access antibiotics declined in most inpatient settings over the study period, it increased for Watch and Reserve antibiotics.
In ICUs, resistance to Watch antibiotics increased from 15% to 33%, and resistance to Reserve antibiotics rose from 9% to 32%.
Resistance to Watch and Reserve antibiotics was highest in children aged 0 to 2 years, children with sepsis, and those with respiratory infections.
In Africa and Southeast Asia, resistance to Reserve antibiotics in Klebsiella species rose to 33% and 43%, respectively.
New research indicates that antimicrobial resistance (AMR) rates have increased significantly in children over the last two decades, rendering many first-line treatment options ineffective and now increasingly threatening second-line and last-resort options.
In an analysis of more than 100,000 bacterial isolates collected from children in hospitals wards, intensive care units (ICUs), and outpatient settings around the world, researchers found that more than a third were resistant to at least one first-line antibiotic, and roughly one in five were resistant to second-line antibiotics.
AMR is especially high in ICUs, in the youngest children with the most severe infections, and in resource-limited settings, the study found. But it’s a problem everywhere, and projections indicate it’s likely to get worse in the coming years.
The authors of the study, published earlier this week in JAMA Pediatrics, say the findings should be a “wake-up call.”
“There’s really no area of the world that isn’t seeing an increase” in resistance, Penelope Bryant, PhD, MBBCh, corresponding author and research clinician at Murdoch Children’s Research Institute in Australia, told CIDRAP News. “And it’s going to continue to increase unless we turn it around.”
An ‘invisible’ problem
Bryant, who collaborated with researchers from the University of Sydney, Brown University, and the Clinton Health Access Initiative (CHAI), said the idea behind the study was not to be alarmist but to alert people to a growing problem that doesn’t get much attention.
While there has been increasing attention to drug-resistant infections in newborns in low- and middle-income countries (LMICs), there’s not much data on AMR in children beyond that vulnerable population.
“I think part of the problem with childhood antibiotic resistance is it's invisible,” she said. “People don't really see it as a problem partly because children have stronger immune systems once they get beyond the neonatal period.”
To fill part of the data gap, the researchers analyzed data from the Antimicrobial Testing Leadership and Surveillance (ATLAS) database, which includes pediatric bacterial isolates collected from children aged 0 to 18 in 82 countries from 2004 to 2022. They focused on “priority pathogens” identified by the World Health Organization (WHO) and assessed resistance trends using the WHO’s Access, Watch, and Reserve (AWaRE) antibiotic classification system.
Antibiotics in the Access group are first-line, narrow-spectrum drugs recommended for most common bacterial infections. The Watch and Reserve categories are for broader-spectrum antibiotics that should be limited to treatment of more serious infections to preserve their effectiveness.
There’s really no area of the world that isn’t seeing an increase...and it’s going to continue to increase unless we turn it around.
Of the 106,581 isolates included in the study, nearly three-quarters were from hospital wards (47%) and ICUs (27%). The most frequently identified pathogens were Staphylococcus aureus (19%), Klebsiella species (11%), and Escherichia coli (10%).
Overall, resistance was highest (36%) to Access antibiotics, which are the first-line treatment option for most common bacterial infections, while 22% of the isolates were resistant to Watch antibiotics and 13% to Reserve antibiotics.
But while resistance to Access antibiotics declined in most inpatient settings over the study period, it increased for Watch and Reserve antibiotics. In ICUs, resistance to Watch antibiotics increased from 15% to 33%, and resistance to Reserve antibiotics rose from 9% to 32%. Resistance to Watch and Reserve antibiotics was highest in children aged 0 to 2 years, children with sepsis, and those with respiratory infections.
Resistance to all AWaRE categories was highest in resource-limited regions, including countries in Southeast Asia, Africa, and Central America. In Africa and Southeast Asia, resistance to Reserve antibiotics in Klebsiella species rose to 33% and 43%, respectively. And forecasting to 2035, based on current trajectories, indicates pathogens in those regions will see larger increases in resistance to Watch and Reserve antibiotics.
The higher AMR levels in LMICs isn’t a surprise, given that drug-resistance is higher in general in those settings, due to a combination of high infection burden, poor sanitation and infection control, and unfettered antibiotic access.
“In a large proportion of low-income countries you can buy antibiotics over the counter in pharmacies, and in some countries you can even buy them in markets,” Bryant said. That kind of unregulated use promotes more resistance and limits treatment options, which in some LMICs are already limited.
But high-income countries won’t be spared, Bryant added.
“Bacteria don't recognize country borders and boundaries, and we're increasingly traveling as a global community,” she said. “So this is going to become more of a problem in resource-rich settings as well.”
Clear policy and practice implications
Bryant and her colleagues say the policy and practice implications are clear. Low-resource countries need to crack down on unregulated antibiotic use and improve sanitation and infection control.
All countries need to develop antimicrobial stewardship strategies that target the most severe pediatric infections, like sepsis and pneumonia, and reduce unnecessary antibiotic use in people and animals. And more child-friendly antibiotic formulations are needed, so that children get the correct dose in a more palatable format.
“If we want a different outcome, we need to do something different,” Bryant said.
To create more visibility for the issue, they’ve also used the data from the ATLAS database to develop the AMR in Kids website, which features a dashboard that allows users to explore resistance by country, bacteria, and antibiotic class. The hope is that the site will enable researchers to identify where resistance is likely to emerge, help clinicians make better treatment decisions, and help policymakers develop intervention strategies.
“Better data is essential, but children can’t wait for perfect data. We need to use the best available evidence to guide action now,” study coauthor and CHAI Senior Clinical Director Joseph Harwell, MD, said in a press release.
