Stewardship / Resistance Scan for Nov 08, 2022

News brief

Trial supports shorter regimens for resistant TB

A clinical trial conducted in seven countries found that two shortened, bedaquiline-containing regimens had superior efficacy in treating rifampicin-resistant tuberculosis (TB) compared with a 9-month injectable-containing regimen, with fewer cases of hearing loss, investigators reported today in The Lancet.

The STREAM stage 2 trial randomized patients aged 15 years or older with rifampicin-resistant TB to receive one of four treatments: the long regimen (the 20-month regimen recommended by the World Health Organization from 2011 to 2018), the control regimen (a 9-month regimen with the second-line injectable kanamycin), the oral regimen (9 months with bedaquiline replacing the injectable), and the 6-month regimen (containing bedaquiline and supplemented with 8 weeks of kanamycin). The primary outcome was favorable status (negative cultures for Mycobacterium tuberculosis) at 76 weeks, with additional analysis of serious adverse events.

Of the 517 participants in the modified intention-to-treat (mITT) analysis, 133 of 187 (71%) on the control regimen had a favorable outcome, compared with 162 of 196 (83%) on the oral regimen, for a difference of 11 percentage points (95% confidence interval [CI], 2.9 to 19.0), adjusted for HIV status and randomization protocol. By 76 weeks, 108 of 202 (53%) participants in the control regimen and 106 of 211 (50%) allocated to the oral regimen had an adverse event of grade 3 or 4, with hearing loss more frequent among those who received the control regimen (18 [9%] vs 4 [2%]).

Of the 134 participants in the mITT population who were allocated to the 6-month regimen, 122 (91%) had a favorable outcome, compared with 87 of 127 (69%) assigned to the control regimen, for an adjusted difference of 22.2 percentage points. Six of 143 (4%) recipients of the 6-month regimen had grade 3 or 4 hearing loss.

"In conclusion, STREAM stage 2 has shown that two short-course, bedaquiline-containing regimens are not only non-inferior but superior to a 9-month injectable-containing regimen," the investigators wrote. "These two regimens offer promising treatment options for patients with MDR [multidrug-resistant] or rifampicin-resistant tuberculosis. However, safer and simpler alternatives are still needed."
Nov 8 Lancet study

 

Veterinary antibiotic sales continue to decline in United Kingdom

A report today from the United Kingdom's Veterinary Medicines Directorate (VMD) shows that sales of antibiotics for use in UK livestock continue to decline.

The data in the 2021 UK Veterinary Antibiotic Resistance and Sales Surveillance Report (UK-VARSS) show that sales of antibiotics for use in food-producing animals, adjusted by animal population, fell by 6% compared with 2020 and 55% compared with 2014. Sales of highest-priority critically important antibiotics (HP-CIAs), which are considered the most vital antibiotics for human medicine, fell by 18% compared with 2020 and 83% compared with 2014. They accounted for 0.4% of total antibiotic sales for livestock in 2020—a new low.

The report also showed that antibiotic usage, including use of HP-CIAs, in 2020 fell across most animal species, with some increases observed in turkeys, game birds, and salmon. Use of HP-CIAs in UK pigs has fallen by 97% since 2015, and by 96% in UK poultry since 2014.

Clinical surveillance of antimicrobial resistance (AMR) in Escherichia coli from animal species shows some encouraging trends as well. Of the HP-CIAs tested, resistance to fluoroquinolones and third-generation cephalosporins was low or not detected for any animal species tested in 2021. In addition, the number of Salmonella isolates from cattle, pigs, chickens, and turkeys that were fully susceptible to the panel of antibiotics tested increased in 2021.

But the report does note an increase in the percentage of pigs carrying extended-spectrum beta-lactamase (ESBL)/AmpC-producing E coli, which are resistant to third-generation cephalosporins.

"Surveillance of antibiotic consumption and antibiotic resistance is one of the central pillars of the work we do on AMR," VMD Head of AMR Policy and Surveillance Kitty Healy, PhD, MRCVS, wrote in the forward to the report. "It has the potential to be more valuable still as we strive to continuously enhance our own surveillance programmes, and to link them with similar programmes in people, food, the environment and beyond."
Nov 8 UK VARSS report

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News Scan for Nov 08, 2022

News brief

22% of kids with COVID-19 or MIS-C had neurologic involvement in 2020-21

A study of US patients aged 0 to 20 years hospitalized for COVID-19 or multisystem inflammatory syndrome in children (MIS-C) in 2020 and 2021 shows that 22% had a neurologic condition, including 9% with life-threatening illness.

In the study, published yesterday in JAMA Neurology, a team led by Boston Children's Hospital researchers investigated rates of neurologic disorders in 2,168 children admitted to 55 hospitals in 31 states from Dec 15, 2020, to Dec 31, 2021, for COVID-19 (34%) or MIS-C (66%). Median patient age was 10.3 years, and 58% were male.

Of all patients, 22% had neurologic involvement, 9% of whom had life-threatening conditions, including 55% who had acute central nervous system (CNS) infections or acute disseminated encephalomyelitis (ADEM; damage to the protective covering of nerve fibers in the brain). The most common of these conditions were encephalitis (infection-related swelling of the brain) and stroke. Seven of 23 (30%) of these patients experienced severe outcomes.

Life-threatening neurologic disorders were more common during the Delta variant surge than in previous waves (64% vs 36%). Ten of 42 (24%) of patients with neurologic involvement were released from the hospital with new-onset neurologic conditions, and 8 (19%) died. Among patients with non–life-threatening neurologic involvement, 4% were released from the hospital with neurologic deficits, 90% had no neurologic disorders, and 5% died.

Relative to patients with no neurologic involvement, those with such a condition were older (median age, 12 vs 10 years) and more often had underlying neurologic disorders (107 of 476 [22%] vs 240 of 1,692 [14%]).

Of the 155 COVID-19 vaccine-eligible patients with neurologic involvement and confirmed vaccination status, 95% had received no doses, including 15 of 16 patients (94%) with life-threatening illness.

"SARS-CoV-2–related neurologic involvement in US children and adolescents hospitalized for COVID-19 or MIS-C persisted in 2021, and acute CNS infection/ADEM accounted for more of the reported life-threatening cases than in 2020," the researchers wrote. "COVID-19 vaccination is effective at preventing hospitalization for acute COVID-19 and MIS-C and may decrease associated neurologic complications."
Nov 7 JAMA Neurol study

 

Study: Cholesterol drug has no significant effect on COVID-19

After showing promise in early laboratory research, the cholesterol-lowering drug fenofibrate had no significant effect on COVID-19 outcomes in a multicenter international randomized controlled trial, where use of the drug did little to curb severity of disease or deaths. The study is published in Nature Metabolism.

The large study was performed by researchers from Penn Medicine, who sponsored the FERMIN trial at 26 collaborating institutions from North America, South America, Europe, and Western Asia.

Fenofibrate is a low-cost generic drug approved for use around the world, and works to lower fatty substances such as cholesterol and triglycerides in the blood. In previous lab studies, fenofibrate reduced viral replication by changing how cells handled fat.

To conduct the study, researchers enrolled 701 participants who reported COVID-19 symptoms in the previous 2 weeks. The study team assigned 351 patients to be treated with 145 milligrams of fenofibrate and 350 with a placebo.

Those in the intervention arm had no significant reductions in symptom severity up to 30 days following the trial. There was no significant effect on death from any cause. Importantly, these outcomes were seen in all countries and trial sites, and among all participants regardless of sex, age, comorbidities, and body mass index.

According to the study authors, there were 61 (17%) adverse events in the placebo arm compared with 46 (13%) in the fenofibrate arm, with slightly higher incidence of gastrointestinal side effects in the fenofibrate group.

In a press release, Jordana B. Cohen, MD, MSCE, a professor at Penn said, "Cellular effects of drugs observed in a petri dish system may fail to translate to beneficial effects in people with COVID-19 as a result of a wide range of potential phenomena in whole organisms. Our trial reinforces the importance of not equating laboratory efficacy with clinical efficacy in the setting of COVID-19."
Nov 7 Nat Metab study
Nov 7 Penn Medicine
press release

 

USDA researchers say deer susceptible to scrapie, a relative of CWD

US Department of Agriculture (USDA) researchers in Ames, Iowa, published a new study showing white-tailed deer are susceptible to the prion that causes classical scrapie in sheep, and that differentiation from chronic wasting disease (CWD) may be difficult. The study is published in the Journal of Infectious Diseases.

To conduct the study, the researchers took five healthy white-tailed deer and inoculated them by a concurrent oral/intranasal exposure with the classical scrapie agent from sheep. Another six deer were inoculated oronasally with the classical scrapie agent from goats.

None of the animals inoculated with scrapie from goats showed signs of prion disease, but all the animals inoculated with the prion disease from sheep had clinical signs of infection, spongiform lesions, and widespread evidence of disease in neural and lymphoid tissues.

"This study suggests that potential transmission of scrapie to deer presents an ongoing risk to wild and captive white-tailed deer. Future studies will focus on whether white-tailed deer could serve as a reservoir of infectivity to scrapie susceptible sheep," the authors concluded.

While neither scrapie nor CWD have been documented in humans, another prion disease, called bovine spongiform encephalopathy (BSE, or "mad cow" disease) poses a threat to people who consume BSE-infected animals, and officials are concerned the same may happen with CWD.
Nov 8 J Infect Dis study

 

Cases and deaths rise in Uganda's Ebola outbreak

Over the past few days, Uganda has reported 5 more Ebola cases, along with 5 new deaths, according to the latest totals on the health ministry's website. The newest developments bring the number of lab-confirmed cases to 136 and the number of deaths in people with confirmed infections to 53 in the current outbreak.

The outbreak, first announced in September, involves the less common Sudan Ebola virus.

In other outbreak developments, the country's Cabinet has approved a health ministry plan to close schools early for the third-term holidays to curb the Ebola outbreak, according to the Daily Monitor.

Also, over the weekend, the government extended the 3-week lockdowns for two of the hardest hit districts, Mubende and Kassanda, according to Agence France-Presse (AFP). The lockdowns are slated to last another 3 weeks and include a night curfew, a ban on personal travel, and the closure of markets, bars, and churches.
Uganda health ministry Ebola page
Nov 8 Daily Monitor story on
school measures
Nov 5 AFP
story

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