Stewardship / Resistance Scan for Jan 11, 2022

News brief

Review finds too few innovative drugs in antibiotic development pipeline

A new review of the antibiotic development pipeline finds that there are relatively few clinically differentiated products in late-stage clinical development, especially against critical, multidrug-resistant pathogens, an international team of researchers reported yesterday in Antimicrobial Agents and Chemotherapy.

The review, which looked at all traditional and non-traditional antibacterial drug candidates that were being evaluated in clinical trials as of Jun 30, 2021, found a total of 76 products, 45 of which are traditional antibacterial agents and 31 of which are non-traditional. Sixty of those candidates (79%) are in phase 1 (28) or phase 2 (32) trials, with 12 in phase 3 trials and 4 under regulatory review.

Of the 76 candidates, 42 are being developed to target the pathogens deemed critical (26) and high/medium priority (16) by the World Health Organization. In addition, 16 products are being developed to treat mycobacterial infections (14 for tuberculosis and 2 for non-tuberculosis mycobacteria) and 15 to treat Clostridioides difficile infections. But only 18 of the antibacterial agents in development have new pharmacophores, which is one of the components that can determine whether an antibacterial candidate belongs to a new class or sub-class of antibiotics, and only 4 have new, overarching modes of action.

The review also found that 12 new antibacterial products have been approved globally since 2017, but only 1 (vaborbactam) belongs to a new antibiotic class.

While the review authors note that the overall number of antibacterial candidates being evaluated in clinical trials is promising, the small number of clinically differentiated agents targeting priority pathogens that are in late-stage development, and the dearth of innovative new products, remains a problem. They say there needs to be a research and development (R&D) focus on "quality over quantity" to address increasing numbers of multidrug-resistant infections.

"It is important to try and keep on identifying and developing antibacterial agents with new modes of action to try and slow down antibacterial drug resistance," they wrote. "Furthermore, we believe that future antibacterial R&D should focus on the development of innovative and clinically differentiated candidates that have clear and feasible progression pathways right through development and onto the market."
Jan 10 Antimicrob Agents Chemother abstract

Collaboration aims to boost use of diagnostics to combat resistance

Medical technology company BD (Becton, Dickinson and Company) today announced a partnership with pharmaceutical company Pfizer and global nonprofit Wellcome to explore the role diagnostics can play in advancing antimicrobial stewardship and combating antimicrobial resistance (AMR).

The collaboration will survey existing diagnostic practices in healthcare settings to highlight the benefits of diagnostic testing for stewardship, as well as the gaps. Proper use of diagnostic testing to distinguish between bacterial and viral infections can play a critical role in reducing unnecessary antibiotic and antifungal use and slowing the emergence of AMR, but diagnostics remain underused, company officials said in a press release.

"Diagnostic stewardship—meaning coordinated guidance and interventions to improve appropriate use of microbiological diagnostics to guide therapeutic decisions—promotes appropriate, timely diagnostic testing, including specimen collection and pathogen identification as well as accurate, timely reporting of results to guide patient treatment," said Brooke Story, MBA, president of Integrated Diagnostic Solutions for BD.

"Research shows us that significant barriers must be overcome to make health care workers aware of the importance and positive impact of diagnostics on AMR."

Gemma Buckland-Merrett, PhD, research lead for drug-resistant infections at Wellcome, said the collaboration will help address these challenges and contribute to better outcomes for patients and the healthcare system. "Having the right diagnostic tools for the right contexts, and ensuring their uptake is crucial to fight antimicrobial resistance and save modern medicine," she said.
Jan 11 BD press release

News Scan for Jan 11, 2022

News brief

Federally qualified centers helped address COVID vaccine gaps: report

US Federally qualified health centers (FQHCs) have been critical to providing COVID-19 vaccinations to low-income and racial minority populations, finds a study yesterday in JAMA Network Open.

Boston University researchers led the analysis of data from national COVID-19 surveys and 1,096 FQHCs that served 25.9 million US patients from Jan 8 to Jul 2, 2021. The Health Center COVID-19 Vaccine Program gave FQHCs, which provide primary care to underserved communities, large numbers of vaccines to help address vaccine disparities.

Of the 25.9 million patients, 0.7% were American Indian or Alaska Native, 2.9% were Asian, 17.5% were Black, 42.0% were Hispanic, 34.9% were White, and 2.0% were of other races. The proportion of Black and Hispanic patients who sought vaccines at FQHCs increased over time.

COVID-19 vaccines were equitably given to American Indian, Alaska Native, Asian, and Hispanic patients (statistical equity ratio, 1.0 or higher), and 61.4% of vaccines were administered to people of color, compared with 40% of those given to racial minorities in the general US population.

Disparities among Black patients persisted (statistical equity ratio, 0.94), but they were smaller than those in the rest of the US Black population.

"These populations may not otherwise have easy access to a vaccine clinic, or may not trust other types of institutions with histories of racism or that have systematically failed them," lead author Megan Cole Brahim, PhD, MPH, said in a Boston University press release.

The authors noted that addressing COVID-19 vaccine racial disparities is vital to curbing disease transmission. To that end, they said, the government should continue to fund and prioritize the use of FQHCs as vaccine providers.

"This includes direct allocation of vaccines; use of FQHC-based mobile clinics, pop-up vaccination sites, and school-based sites; and targeted outreach for Black and Hispanic patients, including pediatric populations," the researchers concluded.
Jan 10 JAMA Netw Open research letter
Jan 10 Boston University press release

Fourth COVID vaccine dose boosts immunity in kidney transplant patients

A fourth dose of an mRNA-based COVID-19 vaccine produces a good antibody response in half of kidney transplant recipients who did not respond adequately after three doses, according to a study involving 92 transplant patients yesterday in Annals of Internal Medicine.

Researchers from the University Hospital of Strasbourg, France, gave a fourth vaccine dose to patients who had low (less than 143 binding antibody units per milliliter [BAU/mL]) anti-spike immunoglobulin G (IgG) titers 1 month after a third dose. Fifty-eight received the Moderna vaccine and 34 the Pfizer-BioNTech vaccine.

The investigators then measured anti-spike IgG titers 2 to 6 weeks later. They reported that, after a median of 29 days, median anti-spike IgG levels increased from 16.4 BAU/mL (interquartile range, 5.9 to 62.3 BAU/mL) to 145 BAU/mL (interquartile range, 27.6 to 243 BAU/mL), suggesting that a fourth dose of vaccine may be warranted in these patients.

Half the patients reached the threshold of 143 BAU/mL, and those who received Moderna had higher IgG titers (median, 150 vs 122 BAU/mL). The researchers also found no safety concerns with the additional dose.

Only one patient was subsequently diagnosed with mild COVID-19, and he had an anti-spike IgG level of only 28 BAU/mL 1 month after the fourth dose.

The study authors conclude, "We recognize that an increase in antispike IgG titers does not invariably provide protection from infection and disease, which is why we encourage longitudinal studies with a sufficient duration of follow-up."
Jan 10 Ann Intern Med study