News Scan for Dec 22, 2021

News brief

New metric aims to capture antibiotic prescribing among pediatricians

A team of pediatricians in Massachusetts has developed a new metric for capturing the range of antibiotic prescribing among pediatricians for common clinical scenarios.

The Antibiotics Likelihood Index (ALI), described in a paper last week in the Journal of the Pediatric Infectious Diseases Society, was developed using data from 2018 and 2019 for children ages 3 months to 17 years from 53 practices in a large pediatric network in Massachusetts. Based on those data, the clinicians grouped encounters into Reason for Visit categories and then analyzed the proportion of encounters with an antibiotic prescription within each category.

The ALI was defined as the proportion of encounters with an antibiotic prescribed among categories that accounted for more than 80% of encounters with an antibiotic prescribed.

Analysis of the 2018 data showed that six Reason for Visit categories—cough, ear complaints, fever, sore throat, rash, and congestion/upper respiratory infection—accounted for 82.4% of all antibiotics prescribed. Among the 222,682 encounters for the top 6 categories combined, 30.3% had an antibiotic prescribed, defined as the ALI for the entire sample. The authors repeated the analysis for the 2019 data and found similar results, with an overall ALI of 30.8%. The index among individual prescribers for 2018 ranged from 7.5% to 57.2%, and for 2019 it ranged from 9.9% to 60.2%.

The authors say the strengths of the ALI compared to other proposed metrics of antibiotic prescribing are that it varies very little according to patient demographic factors such as age, sex, and insurance type, and it allows for a fair comparison of one pediatrician's overall antibiotic prescribing to another.

"Further research to validate the ALI construct within other pediatric primary care networks would be helpful to establish the generalizability of this approach," they wrote.
Dec 18 J Pediatric Infect Dis Soc abstract

Sepsis management bundle not tied to more antibiotics or fewer deaths

An analysis of data on sepsis patients found that adherence to a federally mandated sepsis management bundle in US hospitals was not associated with a change in already increasing rates of broad-spectrum antibiotic use or with improved mortality rates, researchers reported this week in JAMA Network Open.

The retrospective study, conducted among 117,510 adults admitted to 114 hospitals with suspected sepsis from October 2013 to December 2017, aimed to analyze the impact of implementing the 2015 Centers for Medicare and Medicaid (CMS) Severe Sepsis and Septic Shock Early Management Bundle (SEP-1).

While SEP-1 has catalyzed widespread sepsis quality improvement efforts, the study authors note, concerns have been raised that the bundle, which requires clinicians to administer broad-spectrum antibiotics to suspected sepsis patients within 3 hours, would lead to inappropriate use of broad-spectrum antibiotics. There have also been concerns that the bundle has increased detection of milder sepsis cases, which may affect mortality rates.

The primary outcome of the interrupted time series and logistic regression analysis was quarterly rates of risk-adjusted short-term mortality. Secondary outcomes included administration of anti–methicillin-resistant Staphylococcus aureus (MRSA) or antipseudomonal beta-lactam antibiotics within 24 hours of hospital arrival.

While there were increases in the use of anti-MRSA antibiotics (19.8% in Quarter 4 of 2013 to 26.3% in Q4 of 2017) and antipseudomonal antibiotics (27.7% in Q4 of 2013 to 40.5% in Q4 of 2017), these trends preceded SEP-1 and did not change with SEP-1 implementation. Unadjusted short-term mortality rates were similar in the pre–SEP-1 period (Q4 of 2013 through Q3 of 2015) versus the post–SEP-1 period (Q1 of 2016 through Q4 of 2017) (20.3% vs 20.4%), and SEP-1 implementation was not associated with changes in level (OR, 0.94; 95% confidence interval [CI], 0.68 to 1.29) or trend (OR, 1.00; 95% CI, 0.97 to 1.04) for risk-adjusted short-term mortality rates.

"These findings suggest that alternate approaches to improving mortality for patients with sepsis are warranted," the authors wrote.
Dec 20 JAMA Netw Open study

WHO: Global flu continues slow rise

Overall flu activity remains low but continues to pick up, especially in parts of the Northern Hemisphere, the World Health Organization (WHO) said in its latest global flu update. It urged countries to enhance surveillance for flu alongside COVID-19 monitoring, and it recommended that countries step up their flu vaccination activities.

Both influenza A and B are circulating, with the H3N2 strain predominant in North America and Europe. East Asia's flu activity shows a rise, led mostly by influenza B. In South America, Brazil reported H3N2 activity, and it—along with several other countries—still report respiratory syncytial virus (RSV) activity.

Globally, over the 2 weeks spanning late November into early December, 58.1% of respiratory samples that tested positive for flu were influenza A, and 41.9% were influenza B. Of the subtyped influenza A samples, 90.1% were H3N2. And all characterized influenza B samples belonged to the Victoria lineage.
Dec 20 WHO global flu update

COVID-19 Scan for Dec 22, 2021

News brief

Unvaccinated at up to 4 times the risk of symptomatic COVID infection

People unvaccinated against COVID-19 were at up to four times the risk of infection, finds a JAMA Network Open study based on tests taken at US retail pharmacies, most of them after the emergence of the Delta (B1617.2) variant.

Researchers from CVS Health in Rhode Island analyzed the incidence of symptomatic COVID-19 infections diagnosed in 1,237,097 adults at 4,094 CVS pharmacies from May 1 to Aug 7, 2021. Median patient age was 37 years.

Of the 1,237,097 adults, 52.2% were unvaccinated and 47.8% were vaccinated. Of the vaccinated, 56.7% had received the Pfizer/BioNTech (BNT162b2) COVID-19 vaccine, while 35.0% received Moderna (mRNA-1273), and 8.3% received Johnson & Johnson (J&J).

Adjusted estimated vaccine effectiveness against COVID-19 infection for those who had received two doses of the Moderna or Pfizer mRNA vaccines peaked after 2 weeks (96.3% for Moderna, 92.4% for Pfizer), then declined to 86.8% and 78.6%, respectively, at 2 to 3 months and 74.2% and 66% after 6 months in multivariable analyses. Adjusted vaccine effectiveness for one dose of the J&J vaccine remained higher than 50% after 2 weeks.

Patients who received the Pfizer or Moderna vaccines had the lowest incidence of COVID-19 infection throughout the study, while the unvaccinated had the highest. The unvaccinated had 412% more infections than those who received the Moderna vaccine, 287% more than those who received the Pfizer vaccine, and 159% more than J&J recipients.

Incidence of COVID-19 infection was 24.8% among the unvaccinated, 15.6% in the J&J group, 8.6% in the Pfizer group, and 6.0% among Moderna recipients. In July and August, the risk of infection in both unvaccinated and vaccinated participants increased with the rising incidence of Delta cases.

The researchers noted that the cases included in the study were likely less severe, given that they were diagnosed at a retail pharmacy.

"Although our data indicate that vaccine effectiveness gradually wanes over time, the 2-dose mRNA vaccines remained estimated 74% (mRNA-1273) and 66% (BNT162b2) effective against symptomatic SARS-CoV-2 infections 6 months or longer after 2 doses during a period in which the Delta variant became the dominant strain," they wrote.
Dec 22 JAMA Netw Open research letter

Convalescent plasma cuts COVID hospital cases in half, clinical trial shows

Early treatment with concentrated convalescent plasma halved the need for hospitalizations for COVID-19 outpatients, according to a randomized, controlled trial published yesterday on the preprint server medRxiv.

The study, led by Johns Hopkins University researchers and not yet peer-reviewed, compared the effectiveness of concentrated (high-titer) convalescent plasma to a placebo in 1,225 symptomatic adult COVID-19 patients at 23 US sites. Convalescent plasma from blood donated by COVID-19 survivors is rich with antibodies against SARS-CoV-2 infection.

Of the 1,225 patients randomly assigned to convalescent plasma or placebo from Jun 3, 2020, to Oct 1, 2021, 1,181 received a transfusion within 9 days of COVID-19 symptom onset. Median patient age was 44 years, 7% were at least 65 years old, 35% were 50 or older, 57% were women (including 3 who were pregnant), Black and Hispanic participants each made up over 10% of the population, and 2% were American Indian or Native Pacific Islander.

Thirty-seven of 589 (6.3%) who received a placebo were hospitalized within the following 28 days, compared with 17 of 592 (2.9%) who received convalescent plasma, for a relative risk of 0.46, corresponding to a 54% risk reduction.

The trial was stopped early after enrolling over 90% of its target after fewer hospitalizations were observed among participants (5 to 6 hospitalizations among the first 1,000 enrollees, versus less than 1 per 100 enrollees thereafter).

"Early administration of high titer SARS-CoV-2 convalescent plasma reduced outpatient hospitalizations by more than 50%," the study authors wrote. "High titer convalescent plasma is an effective early outpatient COVID-19 treatment with the advantages of low cost, wide availability, and rapid resilience to variant emergence from viral genetic drift in the face of a changing pandemic."

In a Johns Hopkins news release, co-lead author Kelly Gebo, MD, MPH, said that concentrated convalescent plasma is another tool in the COVID-19 armamentarium. "We believe that the best role for COVID-19 high-titer convalescent plasma is extending its use to early outpatient treatment when other therapies, such as monoclonal antibodies or drugs, are either not readily available—as in low- and middle-income countries—or ineffective—as with SARS-CoV-2 variants that are resistant to certain monoclonal antibodies," she said.
Dec 21 medRxiv study
Dec 21 Johns Hopkins news release

Study finds COVID-19 vaccination in pregnancy passes antibodies to baby

Yesterday a study in JAMA Pediatrics suggested that COVID-19 vaccination in the second trimester of pregnancy was associated with a maternal humoral antibody response that is sustained during labor and transfers antibodies to the newborn.

The cohort study of 130 pregnant women, who completed the Pfizer-BioNTech vaccine series in the second trimester of pregnancy, were seen in Haifa, Israel, from May to July 2021. The mean gestational age at administration of the second vaccine dose was 24.9 weeks.

Antibody levels were tested in newborns within 30 minutes of delivery, with 100% of those tested showing positive results. According to the authors, neonatal IgG titers were 2.6 times higher than maternal titers (median [range], 3315.7 [350.1 to 17,643.5] AU/mL vs 1185.2 [146.6 to 32,415.1] AU/mL), and a positive correlation was seen between maternal and neonatal antibodies (r = 0.92; 95% confidence interval, 0.89 to 0.94).

"Univariable analysis demonstrated correlation of maternal and newborn SARS-CoV-2 IgG [immunoglobulin G] antibody titers at delivery with maternal age, gestational age at the second vaccine dose, and duration from the second vaccine dose to birth," the authors said.

For each 1-year increase in the maternal age, antibody levels in both mothers and babies dropped by 3.9%. For each 1-week increase in gestational age at the second vaccine dose, maternal and newborn antibody levels increased by 10.5%.

"The current study found a maternal and newborn immune response at birth associated with vaccination during the second trimester, suggesting an advantage of early vaccination during pregnancy rather than during the third trimester," the authors concluded.
Dec 21 JAMA Pediatr study