The Food and Drug Administration (FDA) today announced it has approved AstraZeneca's monoclonal antibody nirsevimab-alip (Beyfortus) to prevent respiratory syncytial virus (RSV) in newborns and toddlers.

In its announcement, the FDA said the drug is indicated for newborns and babies entering their first RSV season and for children up to 2 years old who remain vulnerable to severe disease in their second RSV season.

Some infants, especially with their first RSV infection, can experience lower respiratory tract symptoms such as pneumonia and bronchiolitis. The FDA said premature babies, those with lung problems, and infants with congenital heart disease are most at risk for severe RSV infection.

Today’s approval addresses the great need for products to help reduce the impact of RSV disease.

John Farley, MD, MPH, who directs the office of infectious diseases with the FDA's Center for Drug Evaluation and Research, said RSV typically results in many emergency department and doctor's office visits each year. "Today’s approval addresses the great need for products to help reduce the impact of RSV disease on children, families, and the health care system."

The drug is given as a single intramuscular injection before or during RSV season, and its safety and efficacy was established during three clinical trials. The FDA had given Beyfortus fast-track designation to expedite the review.

Adviser to weigh in next month

A Centers for Disease Control and Prevention (CDC) advisory group is expected to meet in August to recommend which patients should receive the drug, according to ABC News.

Nirsevimab-alip is the second monoclonal antibody for preventing RSV in young children. The first drug, palivizumab, is recommended by the American Academy of Pediatrics for certain high-risk infants and young children and must be given monthly during RSV season, according to the CDC.

mRNA COVID-19 vaccines induced an antibody response in both mothers and babies for at least 6 months after birth, with no adverse outcomes, according to a single-center study published late last week in JAMA Network Open.

University of California researchers evaluated the medical records of 76 COVID-naïve mothers in San Francisco who received an mRNA vaccine during pregnancy from December 2020 to December 2021, with follow-up through March 2022.

Mothers gave blood samples before vaccination and after each dose and completed an online questionnaire about adverse effects 28 days after doses. The team also measured immunoglobulin G (IgG) concentrations in umbilical cord blood at delivery and in infant blood and IgG and immunoglobulin A (IgA) levels in breast milk four times for 1 year.

Average maternal age was 35 years, 67.1% were White, 55.3% received the Pfizer/BioNTech vaccine, 44.7% received the Moderna version, and the median gestational age at first dose was 22.8 weeks.

Systemic vaccine-related symptoms tied to higher IgG

Systemic vaccine-related symptoms were more common after the second vaccine dose than after the first (71.2% vs 44.1%) and after the Moderna than the Pfizer vaccine (92.6% vs 53.1%). Systemic symptoms were tied to 65.6% higher median IgG concentrations than no symptoms after dose two, and average cord levels in participants with symptoms were 6.3-fold higher than in those with no symptoms.

Systemic symptoms after receipt of a vaccine dose may indicate a more robust immune response.

While vaccination in all trimesters triggered a robust maternal IgG response, the IgG transfer ratio was highest among those vaccinated in the second trimester. IgG was also detected in cord blood in all trimesters. IgG and IgA concentrations in breast milk remained positive for at least 5 or 6 months after birth, and infants born to women vaccinated in the second and third trimesters had positive IgG levels over the same period. No vaccine-attributed adverse outcomes occurred.

"Systemic symptoms after receipt of a vaccine dose may indicate a more robust immune response, as measured by higher antibody titers," the study authors wrote. "The association between postvaccination symptoms and magnitude of immune response warrants further study."

A new study based the body mass indexes (BMIs) of the residents of Monroe County, Indiana, shows the pandemic was tied to increased rates of severe obesity for children, with the greatest increase among those ages 5 to 11. The study is published in JAMA Network Open.

To conduct the study, researchers looked at the medical records of 27,093 participants ages 2 to 19, with an average age of 9.8 years. BMIs for 2019, 2020, and 2021 were compared. Monroe County's population in 2020 was roughly 148,000, including 22,000 children ages 2 to 19.

Overall severe obesity, defined as a BMI of 40 or high, was higher in 2020 (5.9%), and 2021 (6.3% of participants) compared to 2019 (5.1% of children). Additionally, total unhealthy BMI prevalence (overweight, obesity, and severe obesity) was also higher in 2020 (33.6%) and 2021 (32.9%) compared with 2019 (31.9%).

We observed the greatest increase in obesity prevalence among children aged 5 to 11 years.

"We observed the greatest increase in obesity prevalence among children aged 5 to 11 years (vs 2-4 and 12-19 years)," the authors write. "The findings of this cohort study suggest that childhood obesity, especially among US children aged 5 to 11 years, was significantly higher after COVID-19 restrictions were imposed."

The authors said less physical activity, more screen time, and increased consumption of unhealthy food during school closures likely contributed to the increased prevalence of obesity.

A randomized clinical trial found that direct oral penicillin challenge in patients with a low-risk penicillin allergy was non-inferior to the standard-of-care skin test, investigators reported today in JAMA Internal Medicine.

For the trial, investigators in the United States, Canada, and Australia randomly assigned patients with a PEN-FAST score lower than 3 to receive either direct oral challenge with penicillin (the intervention arm) or a skin test followed by an oral challenge (the control arm). While the skin test is the standard-of-care in most countries, it is resource-intensive, and observational data support direct oral challenge, which is the necessary final step to remove the penicillin allergy label. The primary outcome of the trial was a physician-verified positive immune-mediated oral penicillin challenge within 1 hour post-intervention in the intention-to-treat population.

A total of 377 patients (median age, 51 years; 247 [65.5%] female) were included in the analysis, with 187 in the intervention group and 190 in the control group. Most patients had a PEN-FAST score of 0 or 1. The primary outcome occurred in 1 patient (0.5%) in the intervention group and 1 patient (0.5%) in the control group, with a risk difference (RD) of 0.0084 percentage points (90% confidence interval [CI], −1.22 to 1.24 percentage points). The 1-sided 95% CI was below the non-inferiority margin of 5 pp.

Compared with skin testing, a direct oral penicillin challenge is less resource and time intensive, is less expensive, and has the potential to be performed outside of the specialist allergy setting.

In the 5 days following the oral penicillin challenge, 9 immune-mediated adverse events were recorded in the intervention group and 10 in the control group (RD, −0.45 percentage points; 95% CI, −4.87 to 3.96 percentage points). No serious adverse events occurred.

Although many patients report having penicillin allergies, only 95% are truly allergic, thus making penicillin allergy testing an important component of antibiotic stewardship.

"Compared with skin testing, a direct oral penicillin challenge is less resource and time intensive, is less expensive, and has the potential to be performed outside of the specialist allergy setting, providing a scalable approach to address low-risk, unverified penicillin allergy in diverse treatment settings internationally," the study authors wrote.

Antibiotic prescribing in UK dental practices had been slowly declining in the years before the COVID-19 pandemic, but lockdown-related changes in care delivery led to increased levels of prescribing, a team based at the UK Health Security Agency reported today in JAC-Antimicrobial Resistance.

For the study, researchers examined National Health Service databases, comparing the level of antibiotic prescribing in dental practices in the prepandemic years, January 2016 through February 2020, with prescribing levels during Britain's first lockdown, which occurred from March to May 2020. They also tracked antibiotic prescribing in the months following the lockdown. The databases allowed the investigators to examine treatment plans for both face-to-face and remote dental appointments.

For the prepandemic period, the study authors saw a decreasing trend of -0.02 per 1,000 population per month (P < 0.05). In March 2020, however, antibiotic dispensing increased of 0.98 per 1,000 population. Antibiotic prescriptions peaked in June and July 2020 (1.44 per 1,000 population) when restrictions were scaled back.

The team found that by the end of the study period, July 2021, antibiotic dispensing was declining again but had still not returned to prepandemic levels. Dental treatment plans, which had declined sharply during the lockdown period, had also not yet returned to prepandemic levels.

The researchers noted that, unlike the dentistry findings, declines in antibiotic prescribing in UK primary care practices continued, despite the pandemic strains. They noted that the reasons for the increased prescribing in dental settings are probably multifactorial, adding that swelling and pain were the most common primary reasons for antibiotic dispensing and that dentists may have felt less confident diagnosing and treating acute pain remotely.