Antibiotics reserved for serious pediatric infections are steadily losing their effectiveness, according to a large global study. If current trends continue, by 2035, 82% of Acinetobacter baumannii strains are projected to be resistant to carbapenems, while resistance in the Klebsiella genus could rise to 35%.

The findings, published in JAMA Pediatrics, are based on more than 106,000 bacterial isolates collected from children in 82 countries between 2004 and 2022.

Resistance Rises in Critical Care

In the World Health Organization’s (WHO’s) AWaRe classification, the Access group comprises the first-line treatments for common infections, while the Watch and Reserve groups are reserved for severe infections or those caused by multidrug-resistant bacteria. Between 2004 and 2022, it was precisely these last two categories that grew the fastest. In ICUs, Watch-level resistance jumped from 15% to 33%, while Reserve-level resistance rose from 9% to 32%. In children with sepsis, Watch-level resistance rose from 15% to 30%, and Reserve-level resistance from 3% to 26%. In South America, resistance among critical pathogens to third- and fourth-generation cephalosporins already stands at 50% and could reach 79% by 2035.

For Yanhong Jessika Hu, PhD, MD, clinical epidemiologist at The University of Sydney School of Public Health, Camperdown, Australia, and one of the study authors, the findings highlight a historical limitation. Most surveillance systems were built using data from adults. She said, “Pathogens, antibiotic exposure, clinical scenarios, and treatment options differ by age. When children are underrepresented, it becomes difficult to know whether treatment recommendations truly reflect pediatric reality.”

This oversight can lead to an inappropriate response in clinical practice. “Just because a patient is in serious condition doesn’t necessarily mean they have a multidrug-resistant bacterium,” said Marcelo Otsuka, coordinator of the Pediatric Infectology Committee of the Brazilian Society of Infectious Diseases. Meningococcal meningitis, for example, is a potentially fatal infection that remains susceptible to standard treatment regimens.

The choice of empirical treatment depends less on the severity of the condition and more on the context in which the infection was acquired and the likely pathogen, according to Marco Aurélio Sáfadi, MD, PhD, president of the Scientific Department of Infectious Diseases of the Brazilian Society of Pediatrics. In the hospital setting, the main concern is extended-spectrum beta-lactamase (ESBL)-producing and carbapenemase-producing enterobacteria, as well as multidrug-resistant A baumannii and Pseudomonas aeruginosa. In the community, the most notable pathogens are Escherichia coli, which produces ESBL in urinary tract infections, resistant pneumococci, and Staphylococcus aureus.

“Resistance doesn’t occur only within hospitals. Today, we’re also seeing an increase in community-acquired infections,” emphasized Otsuka. The challenge is compounded by the lack of structured microbiology services and pediatric antibiotic susceptibility testing in many departments, as well as the scarcity of studies in children for several of the reserve antibiotics, added Sáfadi.

Hu recommends collecting microbiological samples before starting treatment, using local resistance data to guide empirical therapy, and revising the treatment regimen as soon as the results are available. Review is the critical step. “A culture that is collected but not reviewed within 48-72 hours is of no use,” said Sáfadi. The regimen should be de-escalated when a narrower-spectrum effective option is available and discontinued if a bacterial infection is ruled out. 

In some centers, molecular tests capable of identifying bacteria and resistance genes within a few hours already allow for early treatment targeting in critically ill patients. Although still limited by cost and availability, these tests are gaining ground, particularly in ICUs and cases of severe sepsis, according to experts interviewed by Medscape Medical News.

Curbing the rise in resistance depends on measures that go beyond prescribing. In hospitals, Hu highlights the importance of strengthening antimicrobial stewardship programs, expanding access to rapid diagnostics, and incorporating local resistance data into clinical decisions. Infection prevention and control measures, such as hand hygiene and proper management of invasive devices, are also priorities, especially in neonatal and pediatric ICUs.

In the community, the researcher advocates reducing the unnecessary use of antibiotics without compromising access for those who truly need them, and points to vaccination, basic sanitation, and expanded access to diagnostic methods as strategies that reduce the need for antibiotics and the selective pressure on bacteria.

The projections for 2035 serve as a warning, not an inevitable fate. In some scenarios, antibiotic resistance in the Access group has already stabilized or decreased, a sign that the trajectory can be altered. “Coordinated efforts in surveillance, infection prevention, and the rational use of antimicrobials can substantially change this scenario before the next decade,” concluded Hu.

The study was funded by a grant from the Vivli AMR Surveillance Open Data Re-use Challenge program, from Wellcome. The data were obtained from the ATLAS database, owned by Pfizer, made available by the Vivli platform with independent review. Hu received a grant from Vivli/Wellcome related to the study. 

This story was translated from Medscape’s Portuguese edition.