A study of US pediatric hospitals found that the 2022 amoxicillin shortage resulted in an increase in broad-spectrum antibiotic use, researchers reported today in the Journal of the Pediatric Infectious Diseases Society.

For the study, a team led by researchers from Lurie Children's Hospital of Chicago evaluated changes in antibiotic use at seven US tertiary care hospitals from July 24, 2022, to April 1, 2023. They wanted to see how antibiotic use in children who presented to the emergency department (ED) with symptoms of acute otitis media (AOM; ear infection), pharyngitis, or community-acquired pneumonia (CAP) changed after the US Food and Drug Administration declared a shortage of amoxicillin powder for liquid suspension on October 8, 2022. They defined amoxicillin as narrow-spectrum and amoxicillin/clavulanic acid, cephalexin, azithromycin, clindamycin, and cefdinir as broad-spectrum.

Of the 730,400 pediatric ED encounters, one of the study antibiotics was prescribed in 141,380 (19.3%). Of these, 19,045 (13%), 53,633 (38%), and 6,418 (5%) had diagnoses of pharyngitis, AOM, and CAP, respectively. Among encounters that involved prescribing at least one antibiotic, amoxicillin suspension prescribing significantly increased in the weeks leading up to the FDA announcement, then immediately fell by 30.8%. 

While use of amoxicillin non-suspension (which was not impacted by the shortage) increased by 7.9%, the FDA declaration was also associated with increased use of amoxicillin-clavulanic acid (+13.7%), cephalexin (+3.4%), azithromycin (+0.7%), and cefdinir (+6.4%). 

Concerns about antibiotic resistance

"Our findings support the hypothesis that clinicians adapted to the antibiotic shortage by prescribing second-line, often broader-spectrum, antibiotics for common infections," the study authors wrote. "While adaptability is a crucial strategy for future drug shortages, it raises concerns about antibiotic resistance from inappropriate use of broad-spectrum antibiotics and treatment failure from resultant antibiotic selection, particularly if future shortages are longer or more frequent."

The authors add, however, that they also found a decline in overall antibiotic prescribing during the study period, suggesting there may have been a greater reliance on non-antibiotic treatment strategies. 

"These findings underscore the need for systemic strategies, such as improved manufacturing capacity, international collaboration, and centralized guidance, to manage future drug shortages while maintaining antimicrobial stewardship," they concluded.

Over the past week, 147 more cases were reported in an unexplained outbreak in a remote region of the Democratic Republic of the Congo (DRC), according to the latest data today from the Africa Centres for Disease Control and Prevention (Africa CDC).

At a weekly briefing, Africa CDC Director Jean Kaseya, MD, MPH, said cases are up from 111 reported during the previous week. "This means we have a major public health issue in the DRC," he said. Nearly 42% of the cases have been reported in children younger than 5 years old.

One more death was reported in the previous week, which involved a child younger than 5 years. So far, 32 deaths have been documented at healthcare facilities, and investigations are under way to determine if 44 deaths reported at the community level are related to the outbreak. 

Though malaria was reported in some of the initial samples, the lab investigation into the cause or causes of the outbreak is far from complete, facing difficult obstacles in getting samples to the National Institute for Biomedical Research (INRB) in Kinshasa for testing.

More samples on their way to lab in Kinshasa

An official from the lab told Africa CDC that samples it received on December 7 are poor quality, with blood and serum samples poorly preserved and some showing hemolysis. The lab didn't receive any nasopharyngeal samples.

Kaseya said a team went back to Panzi health zone to collect more samples, which took 3 days due the remote location and difficult road conditions.

Dieudonne Mwamba, MD, PhD, director-general of the National Institute of Public Health within the DRC's health ministry, said the team collected 78 more samples, which includes several types. They are on their way to the lab in Kinshasa. He said officials anticipate more definitive results sometime over the next week.

The estimated effectiveness of the monoclonal antibody drug nirsevimab was 89% against medically attended respiratory syncytial virus (RSV) infection and 93% against hospitalization among children younger than 5 years during the US 2023-24 respiratory virus season, according to a test-negative case-control study led by Centers for Disease Control and Prevention (CDC) researchers.

The researchers, who published the study in JAMA Pediatrics, compared the epidemiologic factors and burden of medically attended RSV-associated acute respiratory illness (ARI) among young children at seven pediatric medical centers in the 2023-24 RSV season with those of 2017 to 2020. 

The team also compared nirsevimab binding-site mutations, which can decrease or increase susceptibility to the drug, in circulating RSV in infants who did and didn't receive the drug. In total, 28,689 children were enrolled: 9,536 in 2023-24 and 19,153 in 2017 to 2020. The median patient age was 15 months.

In 2023-24, nirsevimab (Beyfortus) was one of two new RSV-prevention products recommended to protect infants in their first RSV season; the other was Pfizer's Abrysvo maternal RSV vaccine. 

Higher uptake may reduce RSV burden

During 2023-24, RSV cases made up 23% (2,199 of 9,490) of all medically attended episodes, a proportion similar to those from 2017 to 2020. Hospitalization rates for RSV in 2023-24 were also similar to average 2017 through 2020 seasonal rates (5.0 per 1,000), with the highest rates among children aged 0 to 2 months (26.6/1,000). 

There is a potential for substantial public health impact with increased and equitable prevention product coverage in future seasons.

Low maternal RSV vaccine coverage precluded an evaluation of effectiveness for that product. Ten of 765 case patients (1%) who had RSV and 126 of 851 control patients (15%) without RSV were given nirsevimab. 

Nirsevimab effectiveness was 89% against medically attended RSV and 93% against RSV hospitalization. Of 229 specimens that underwent whole-genome sequencing, no differences were noted in nirsevimab binding-site mutations by nirsevimab receipt status.

"This analysis documented the continued high burden of medically attended RSV-associated ARI among young children in the US," the authors wrote. "There is a potential for substantial public health impact with increased and equitable prevention product coverage in future seasons."