Locus Biosciences announced yesterday that it's received $23.9 million in funding from the Biomedical Advanced Research and Development Authority (BARDA) to continue developing its CRISPR-enhanced bacteriophage therapy for treating urinary tract infections (UTIs) caused by antibiotic-resistant Escherichia coli.

The funding is part of an $85 million contract between BARDA and the North Carolina-based biotechnology company and will be used to advance LBP-EC01—a bacteriophage cocktail engineered with a CRISPR-Cas3 construct that targets the E coli genome—into the second part of the ELIMINATE phase 2 trial. In the first part of the trial, LBP-EC01 in combination with trimethoprim/sulfamethoxazole demonstrated safety and tolerability in patients with uncomplicated UTIs.

Part two of the placebo-controlled trial will evaluate the efficacy of the combination in adult women with uncomplicated UTIs caused by drug-resistant E coli.

Uncomplicated UTIs, 80% of which are caused by E coli, are one of the most common reasons for outpatient antibiotic prescribing in the United States and other parts of the world, affecting more than 150 million people each year. But resistance to first-line antibiotics for uncomplicated UTIs, including trimethoprim/sulfamethoxazole, is rising, and multidrug-resistant uropathogenic E coli has become a growing problem in hospitals and the community.

"Engineered bacteriophage have emerged as one of the most promising technologies for addressing the worldwide public health crisis of multi-drug resistant (MDR) bacterial infections," Paul Garofolo, co-founder and CEO of Locus, said in a company press release. "While multiple small-scale studies have shown promise, the field urgently needs a definitive large-scale placebo-controlled study to conclusively test the efficacy of an engineered bacteriophage therapy."

Prescribers in low- and middle-income countries (LMICs) hold positive attitudes toward antimicrobial stewardship but have suboptimal knowledge, and stewardship programs in those settings face a range of barriers, according to a scoping review published yesterday in Antimicrobial Resistance & Infection Control.

To map and summarize published data on antimicrobial stewardship programs (ASPs) deployed in hospitals in LMICs, researchers in Bangladesh reviewed 182 relevant articles that looked at ASP perceptions, facilitators to ASP development, barriers to ASP implementation, and impacts of ASP interventions. The 84 studies that met the inclusion criteria represented 34 LMICs, with India, China, and Pakistan the most represented countries.

Lack of human resources, lab support, and leadership

The review found that while most prescribers (physicians and pharmacists) in LMICs showed positive attitudes towards ASPs and viewed them as beneficial for both patients and prescribers, many had a suboptimal knowledge of stewardship and its basic principles. Furthermore, many barriers to ASP implementation were identified, with human-resources shortage, lack of microbiology laboratory support, absence of leadership, and limited government support the most frequently reported issues. Facilitators for ASP development included the availability of antibiotic guidelines, ASP protocols, dedicated multidisciplinary ASP committees, and prompt laboratory support.

Most studies (79%) documented a decrease in antibiotic consumption and an improvement in rational antibiotic use after ASP implementation, while 42% reported decreases in the prevalence of multidrug-resistant strains. Fifteen studies reported decreases in hospital procurement costs, savings in antibiotic costs, and declines in hospitalization costs.

"The published data underscores the imperative need for widespread antimicrobial stewardship in LMIC hospital settings," the study authors concluded. "Substantial ASP success can be achieved through increasing human resources, context-specific interventions, the development of accessible antibiotic usage guidelines, and heightened awareness via training and education."

South Dakota's two US senators sent a letter to US Department of Agriculture (USDA) secretary Tom Vilsack and US trade representative Katherine Tai last week asking them to launch discussions on updating trade agreements to allow potential future use of avian influenza vaccines in poultry.

Currently, US trade policies, and that of many other nations, bar the import of poultry where vaccines are used in commercial settings. For example, in late September, the USDA announced restrictions on the import of poultry from France and its trading partners due to its decision to vaccinate meat ducks against highly pathogenic avian influenza (HPAI).

Some countries, including China, routinely vaccinate poultry against HPAI. But others have held back over concerns that the vaccine could mask ongoing circulation. As the current H5N1 clade continues to rack up devastating poultry losses on multiple continents, poultry producers are weighing all control options.

In late December, the World Organization for Animal Health (WOAH) posted a policy brief on poultry vaccination, which said the rapid spread of the virus requires a review of existing control strategies, given that current tools might not be enough. The group had previously endorsed the use of vaccines based on international standards and in its brief said countries can maintain trade while ensuring science-based certification measures.

Republican lawmakers Mike Rounds and John Thune said the outbreaks have impacted 5.3 million birds in South Dakota and have cost the federal government nearly $1 billion. They wrote that they're aware that the USDA's Agricultural Research Service is testing new vaccines to address the latest threat.

"We are hopeful about the benefits of the vaccines being developed, but we remain concerned that the important work of updating the trade agreements will not keep up with the scientific advancements," Rounds and Thune wrote. "As HPAI vaccine research continues, we respectfully request animal health and trade leaders give special consideration to impacted producers."

Today researchers from the University of Michigan published in Open Forum Infectious Diseases more evidence that being vaccinated against COVID-19 significantly reduces the risk of developing long COVID.

The findings come from the Immunity Associated with SARS-CoV-2 (IASO) study, an ongoing prospective cohort study of employees and students of the University of Michigan which began in October of 2020. Participants completed weekly symptom and respiratory illness testing surveys.

In the present study, 3,375 people participated in IASO from October 2020 to December 2022, and 81% of those eligible completed a long COVID survey.

At 90-days post-infection, 8% of vaccinated cases were still reporting symptoms, compared with 27% of unvaccinated cases. Any symptoms were 37% and 69% less common for vaccinated cases at 30- and 90-days post-infection (risk ratio [RR], 0.63; 95% confidence interval [CI], 0.52 to 0.76 and RR, 0.31; 95% CI, 0.22 to 0.42), respectively, the authors wrote.

Less long COVID during Omicron

Experiencing five more symptoms at 30- and 90-days post-infection was 63% and 66% less common for vaccinated participants. The effect of vaccination was stronger when the researchers looked at post-Omicron cases. Among vaccinated Omicron cases, only 6% reported symptoms at 90 days, compared with18% of vaccinated pre-Omicron variant cases.

When we compared infections in vaccinated individuals in the Omicron era to the pre-Omicron era we found a reduction in long COVID prevalence and severity for Omicron.

"When we compared infections in vaccinated individuals in the Omicron era to the pre-Omicron era we found a reduction in long COVID prevalence and severity for Omicron. Thus, the prevalence of long COVID in studies conducted prior to the introduction of Omicron likely overestimate the rates from new infections that would be seen in those populations currently," the authors wrote.

Rates of death, vision loss, and pediatric intensive care unit (PICU) admissions among diabetes patients spiked during the pandemic, finds a systematic review of 138 studies from around the world.

Researchers from the University of Massachusetts (UMass) and the University of Leicester in England analyzed data from 138 studies on the effects of COVID-related disruptions on the clinical outcomes of diabetes patients published from January 2020 to June 2023. The studies, which included more than 1 million diabetes patients, compared prepandemic with pandemic periods.

The studies were from North America (39 studies), Western Europe (39), Asia (17), Eastern Europe (14), South America (4), Egypt (1), Australia (1), and multiple regions (33). 

The review is published in The Lancet Diabetes & Endocrinology.

Increases in all-cause, diabetes-related death

The six studies that examined all-cause death and the 13 on diabetes-related death showed consistent increases in both, with six finding increases in vision loss. Adult and mixed samples indicated a rise in the frequency or severity of diabetic ketoacidosis (a potentially life-threatening complication)—some cases due to new-onset diabetes—among children and adolescents but not adults (69 studies). Data from 35 studies suggested a decline in adult hospitalization but higher rates of diabetes-related PICU admissions.

The data on pediatric ICU admissions and pediatric diabetes ketoacidosis is probably the most striking thing that comes out of this review.

Rates of new-onset type 1 diabetes were higher than expected, and children with this type of disease were much sicker during than before the pandemic. Pandemic-related effects were most evident in females, younger people, and racial minority groups. "Further studies are needed to investigate the longer-term impact of the pandemic … on potential differential impacts, which risk further exacerbating existing inequalities within people with diabetes," the authors wrote.

In a UMass press release, co-lead author Jamie Hartmann-Boyce, DPhil, assistant professor of health policy at UMass, said "The data on pediatric ICU admissions and pediatric diabetes ketoacidosis is probably the most striking thing that comes out of this review," she said. "It was very consistent across countries, and a pediatric ICU admission is a major event for kids and their families."