A study presented late last week at the annual congress of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) shows that antimicrobial resistance (AMR) was linked to the deaths of 3 million children in 2022.
Nearly half of the deaths from AMR-related complications were in children in Southeast Asia and Africa, and many were linked to the use of antibiotics that aren't intended for first-line treatment, according to researchers from the Clinton Health Access Initiative (CHAI) and the University of Melbourne.
Using data from Pfizer's Antimicrobial Testing Leadership and Surveillance (ATLAS) database and the Global Burden of Disease study, the researchers assessed AMR-related deaths in children in 83 countries. They focused on World Health Organization (WHO) priority pathogens and calculated the death burden using the WHO's Access, Watch and Reserve (AWaRe) antibiotic classification system.
The AWaRe system is a tool created by the WHO to monitor and evaluate global use of antibiotics and limit the spread of AMR. 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. In 2019, the WHO launched a campaign to increase the global proportion of Access antibiotic use to at least 60%.
"All countries must strike a balance between ensuring access to life-saving antibiotics and slowing drug resistance by reserving the use of some antibiotics for the hardest-to-treat infections," WHO Director-General Tedros Adhanon Ghebreyesus, PhD, said when the campaign was launched. "I urge countries to adopt AWaRe, which is a valuable and practical tool for doing just that."
But several studies in recent years have found that hitting the 60% goal has been difficult in low- and middle-income countries (LMICs), where the burden of bacterial infections and AMR rates are higher because of poor sanitation and weak infection prevention and control measures. In some cases, broader-spectrum drugs are needed because of resistance to first-line antibiotics. In addition, because diagnostic tools and antimicrobial stewardship programs are often limited in these countries, patients with bacterial infections don't always get the right antibiotic.
Rising use of Watch, Reserve antibiotics
The researchers estimated a total of 3,028,970 AMR-related deaths in children in 7 WHO regions in 2022. Of those, more 752,000 were in Southeast Asia, and more than 659,000 were in Africa. At the same time, they found that from 2019 through 2021, the use of Watch antibiotics increased by 160% in Southeast Asia and 126% percent in Africa.
The use of Reserve antibiotics, which are last-resort drugs meant for the treatment of multidrug-resistant infections, rose by 45% in Southeast Asia and 125% in Africa.
In Southeast Asia, pediatric deaths associated with the use of Watch and Reserve antibiotics accounted for 69% of all AMR-related pediatric deaths. In Africa, they accounted for 80%. Globally, more than 2 million AMR-associated pediatric deaths in 2022 were associated with Watch and Reserve antibiotics.
Analysis of more than 106,000 bacterial isolates, 47% of which were from children under 2, found that resistance patterns varied across priority pathogens, with Escherichia coli showing 30% resistance to Access antibiotics and Klebsiella pneumoniae and Enterobacter cloacae showing rising resistance to Watch and Reserve antibiotics.
Rising resistance to Watch and Reserve antibiotics will ultimately lead to higher treatment failure.
Study coauthor Joseph Harwell, MD, senior clinical director at CHAI, said that while the increasing use of Watch and Reserve antibiotics in Southeast Asia and Africa might be necessary to combat a concurrent rise in resistant infections in these regions, the dramatic rise in their use presents long-term risks, because it promotes more resistance and further limits treatment options.
"Rising resistance to Watch and Reserve antibiotics will ultimately lead to higher treatment failure," Harwell said in an ESCMID press release. "Mortality rates, which are already alarmingly high, will continue to rise significantly, particularly in low- and middle-income countries where access to alternative treatments and advanced medical interventions may be limited.”
Harwell called for "urgent and coordinated action" at the global and regional level, including increased AMR surveillance.
"On a regional level, we urge policymakers to mandate hospital-based antimicrobial stewardship programs in all pediatric healthcare facilities," Harwell said. "Improved age classifications will also enhance our understanding of important differences in resistance rates across the age categories, as well as pediatric-specific resistance mechanisms."
