Stewardship / Resistance Scan for Apr 28, 2021

News brief

ASP network boosts stewardship activity at community hospitals

Community hospitals participating in a collaborative network focused on antibiotic stewardship program (ASP) implementation saw an increase in ASP activities and a decline in antibiotic use over 42 months, researchers reported yesterday in Clinical Infectious Diseases.

In the study, researchers with the Duke Center for Antimicrobial Stewardship and Infection Prevention analyzed ASP practices and antibiotic use at 17 community hospitals belonging to the Duke Antimicrobial Stewardship Outreach Network (DASON). Among the services that hospitals in the network receive are onsite consultation from infectious disease physicians and pharmacists, a shared database for routine feedback and benchmarking of antibiotic prescribing, and educational programs.

ASP practice was assessed using structured interviews, and monthly hospital-level antibiotic use rates were measured in days of therapy (DOT) per 1,000 patient days (PD).

Analyzed data included more than 2.5 million DOT and almost 3 million PD from January 2013 to December 2018. The participating hospitals increased their ASP activities over the study period, with significant increases in the number of hospitals implementing formulary restriction processes (initial 65% vs 94%) and prospective audit and feedback (56% vs 94%).

During the first month after entry in the network, the median rate of all antibiotic use among DASON hospitals was 925 DOT/1,000 PD, with a flat trend over the first 12 months. But after a year, the monthly antibiotic use rate trended down slowly. The relative rate (RR) comparing month 42 to month 13 showed a decline of 5% (RR, 0.95; 95% confidence interval [CI], 0.91 to 0.99). The observed median antibiotic use rate at month 42 was 867 DOT/1,000 PD.

Fluoroquinolone use dropped significantly, while other antibiotic classes demonstrated a non-significant downward trajectory after year one. Large variation was seen in hospital-specific antibiotic use.

"In summary, the DASON model provides distinct advantages for individual hospital ASPs compared to 'going it alone,' including access to stewardship expertise, educational resources, and shared data infrastructure to further optimize program activities," the study authors wrote. "Ultimately, this network served an individual hospital's priorities for program implementation but also produced larger, network-level effects."
Apr 27 Clin Infect Dis abstract

X-Biotix announces suspension of antibacterial research program

Biotechnology company X-Biotix Therapeutics of Waltham, Massachusetts, announced this week that it is suspending its current antibacterial research efforts, citing a lack of funding for early-stage antibiotic research and development (R&D).

X-Biotix was founded in 2016 and has focused on delivering small-molecule, first-in-class antibiotics that target multidrug-resistant gram-negative pathogens and defeat known antibiotic-resistance mechanisms. Among its projects, the company has been working on developing antibiotics that target the LpxA and LpxC enzymes, which play a role in constructing the tough outer membrane of gram-negative bacteria.

The company said it's now changing its strategy and will instead focus on submitting manuscripts that describe its process in identifying and developing novel small-molecule antibiotic scaffolds and on strengthening its intellectual property position. The company also said it will explore out-licensing or new funding opportunities for some of its research programs.

"This issue is driven by a critical lack of sustained sources of funding to support early-stage research in this field, combined with lack of an appropriate market infrastructure to support the successful commercialization of novel antibiotics," Stephen Isaacs, PhD, chairman of X-Biotix, said in a company press release. "Policy makers must enact market-based reforms, including reimbursement reform and commercial 'pull' incentives, in order to revitalize the antibiotics market and drive sustainable investments in antibiotics R&D."

X-Biotix is the latest in a line of companies abandoning antibiotic development because of lack of funding and the broken market for new antibiotics, which do not provide companies with a strong return on investment. According to research from the Pew Charitable Trusts' antibiotic resistance project, private investors poured $9.7 billion into R&D efforts for oncology drugs in 2019, while research into antibiotics received only $132 million.
Apr 26 X-Biotix press release

News Scan for Apr 28, 2021

News brief

COVID-related inflammatory syndrome hits poorer, minority kids harder

Multisystem inflammatory syndrome in children (MIS-C), which has been linked with pediatric COVID-19, may pose higher risks to children in lower socioeconomic statuses or who are minorities, according to a Pediatrics study today.

The study compared MIS-C patients with those who had COVID-19, those who were evaluated for MIS-C but found without, children with febrile illness, children with Kawasaki disease, and healthy children in the state. Everyone included in the cohort was under 21 years and in Massachusetts.

In total, 43 patients had MIS-C. Most (58.1%) were boys and of non-White racial or ethnic descent (44.2% Hispanic, 25.6% Black). The median age was 9.7 years at diagnosis. About two thirds (67.4%) of children with MIS-C had a positive antibody test for COVID-19, and 19 (44.2%) had preexisting comorbidities, with the most common being obesity (17) and asthma (6).

A little more than half of MIS-C patients were in the lowest socioeconomic status (SES) quartile (51.1%) or in the highest social vulnerability index (SVI) quartile (53.5%). The researchers calculated that, compared with the general Massachusetts population, both groups had more than double the risk of MIS-C (SES OR, 2.2; 95% confidence interval [CI], 1.1 to 4.4, and SVI OR, 2.8; 95% CI, 1.5 to 4.1). SES and SVI values were similar between the MIS-C and COVID-19 groups, but patients in the other groups tended to have higher household income.

Black and Hispanic children were independently associated with greater risk. The researchers report that children in the lowest SES quartile who were Black had between an 8.7- and 10.8-fold higher risk of MIS-C compared with White, non-Hisptanic children in the same neighborhood. In the same SES group, Hispanics of any race had an OR of 8.7 to 49.8.

"Steps to ameliorate risk for exposure to COVID-19 are key to limiting incidence of MIS-C," write the researchers. "Identifying neighborhoods in which children are most likely to have COVID-19 exposure can inform public health efforts and may allow for proactive protection of at-risk populations."
Apr 28 Pediatrics study

Pediatric hospitalizations for any cause fell from March to August 2020

All-cause weekly pediatric hospitalizations in the United States decreased 48.3% in the spring and 23.5% in the summer 2020 pandemic months when compared with the median volumes in 2017 to 2019, according to a JAMA research letter yesterday.

The researchers looked at 1,699,911 pediatric hospital admissions from 42 freestanding children's hospitals and found that the weekly median dropped from 12,830 in spring 2017 to 2019 to 7,033 in 2020 and from 11,697 in summer 2017 to 2019 to 9,178 in 2020. Decreases in hospitalizations occurred in all demographics and clinical subgroups.

The smallest percentage change per week was in summer 2020 among teenagers 15 to 18 years (-9.6%), and the largest was among children with low illness severity in spring 2020 (-56.4%). Regarding condition-specific hospitalizations, the largest decrease was found in patients with respiratory failure during spring 2020 (a 2017-19 median of 296, dropping down to 87 in 2020; -167.7%).

The researchers also note that the smallest percentage change per week was in summer 2020 for diabetic ketoacidosis (-0.7% from 2017-19 to 2020), though the change was statistically insignificant. Suicide/intentional injury was the only cause of hospitalization that increased in summer 2020 compared with previous years (+11.8% from 2017-19 to 2020), but that change was likewise not statistically significant.

Potential reasons for the lower hospitalization numbers could be due to social distancing and higher symptom monitoring in children, the researchers conclude.
Apr 27 JAMA study

Study finds low uptake of HPV vaccine in young US men

A research letter yesterday in JAMA shows that less than 20% of US men 18 to 21 years old have had at least one dose of the human papillomavirus (HPV) vaccine.

The study, conducted by researchers at the University of Michigan, was based on data collected during the 2010 through 2018 National Health Interview Surveys. Only 16.2% of men ages 18 to 21 during any year of the survey said they had received one or more doses of the HPV vaccine, compared with 42% of women in that age-group.

Among the young men who did receive at least one dose by the ages of 18 to 21, 29% completed the vaccination series. The percentage of young men receiving one dose increased from 2% in 2010 to 34% in 2018, while in women it increased from 32% to 55%.

The Advisory Committee on Immunization Practice (ACIP) recommends that American boys and girls ages 11 to 12 receive two doses of the vaccine, with a third catch-up dose given by the age of 26 if the vaccination series starts after the age of 15.

The Food and Drug Administration (FDA) approved HPV vaccines for females and males in 2006 and 2009, respectively. Last year the FDA expanded the indication to include protection against oropharyngeal cancer. That cancer, which can affect the throat, tonsils, or back of the tongue, has surpassed cervical cancer as the leading cancer caused by HPV, and 80% of cases are detected in men.

"I don't think that a lot of people, both providers and patients, are aware that this vaccine is actually a cancer-prevention vaccine for men as well as women," said Michelle Chen, MD, the lead author of the study and a clinical lecturer at the University of Michigan, in a university press release. "But HPV-associated oropharyngeal cancer can impact anyone—and there's no good screening for it, which makes vaccination even more important."
Apr 27 JAMA research letter
Apr 27 University of Michigan press release