Stewardship / Resistance Scan for May 18, 2020

News brief

CARB-X to fund development of anti-toxin for recurrent C difficile

CARB-X today announced an award of up to $1.26 million to Facile Therapeutics of Belmont, California, to develop a new oral drug for recurrent Clostridioides difficile infections.

The money will help fund preclinical development of Ebselen, a small-molecule anti-toxin that inhibits a key biochemical function of C difficile toxins A and B, which attack the lining of the intestine. Previous studies showed Ebselen provided protection against severe intestinal damage in mice after they were exposed to virulent C difficile infections. The drug has also been tested in humans in clinical trials for stroke, and although it was not approved for that indication, it was shown to be safe.

"This is a terrific example of an attempt to repurpose a compound for use in the infectious-disease arena," CARB-X chief of research and development Erin Duffy, PhD, said in a press release. "If successful and ultimately approved for use in patients, Facile's project could represent tremendous progress in the prevention of recurrent C. difficile infections, and save many lives."

C difficile infections are traditionally treated with antibiotics, which can cure the infection but also further disrupt the microbiome and clear a path for C difficile bacteria to spread, leading to recurrent infections. At least 20% of patients who get an initial C difficile infection have a recurrent infection.

Facile could receive an additional $17 million if the project achieves certain milestones.

Since its launch in 2016, CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) has awarded more than $222 million to companies developing new treatments and diagnostics for drug-resistant pathogens.
May 18 CARB-X press release

Antimicrobial therapy guide linked to reduced antibiotic use in Spain

Implementation of a rigorous antimicrobial use guide and subsequent interventions were associated with substantial reductions in antibiotic prescribing in Spanish primary care settings, researchers reported in PLOS One.

In a quasi-experimental study, researchers with the Andalusian Public Health Care Service assessed the impact of the Aljarafe Antimicrobial Therapeutic Guide, which was published in 2011 and initially implemented in the Aljarafe Primary Health Care Area before being adopted by the Andalusian Public Health Care System. Andalusia sits at the southernmost tip of Spain.

Interventions carried out following adoption of the guide included the development of electronic decision support tools, local training meetings, regional workshops, creation of targets for rates of antibiotic prescribing, and the establishment of a structured educational antimicrobial stewardship program. Using an interrupted time-series analysis, the researchers measured rates of antibiotic use from 2004 through 2018, calculated in defined daily doses per 1,000 inhabitants per day (DID).

The analysis found that overall antibiotic prescribing rates were trending upward prior to the interventions. But prescribing rates dropped by 28% in the Aljarafe Area and 22% in Andalusia from 2011 through 2018 following the interventions, at rates of -0.90 DID per year (95% confidence interval [CI], -1.05 to -0.75) in Aljarafe, and -0.78 DID (95% CI, -0.95 to -0.60) in Andalusia.

Total penicillin use declined by 33% in Aljarafe and 25% in Andalusia, with amoxicillin clavulanate plummeting by 58% in Aljarafe and 49% in Andalusia. The prescribing of quinolones, which was decreasing before the interventions, continued to decline following interventions, with more pronounced downward trends. Use of cephalosporins also continued to decline, at a lesser extent, following interventions in Andalusia. The rate of macrolide prescribing went from a downward trend to an upward trend from 2011 to 2018.

"Reductions in antibiotic prescriptions were more pronounced in the Aljarafe Area where the guide was developed, and where additional interventions included in the local implementation plan were carried out," the authors of the study wrote. "The impact of interventions in the whole region, although with less intensity than in the Aljarafe Area, was similar in terms of the decrease of prescribing rates and decreasing tendencies."
May 15 PLOS One study

News Scan for May 18, 2020

News brief

Black residents bear brunt of US COVID-19 epidemics, study finds

The nearly 22% of US counties with higher proportions of black people accounted for 52% of COVID-19 cases and 58% of related deaths, according to a study published late last week in the Annals of Epidemiology.

The researchers accessed public data on Apr 13 to compare predictors of COVID-19 infections and deaths in counties with 13% or more black people and those with lower percentages.

Nearly 97% of counties with high proportions of black residents (656 of 677) reported a case of the novel coronavirus, and 49% (330/677) reported a death, compared with 81% of all other counties reporting a case (1,987/2,465) and 28% (684/2,465) reporting a death.

As of Apr 13, officials had reported 283,750 coronavirus cases and 12,748 deaths in counties with high proportions of black residents. In contrast, 263,640 cases and 8,886 deaths had been reported in other counties.

After adjusting for county characteristics such as age, poverty level, rates of underlying illness, and epidemic duration, counties with higher proportions of black people reported more COVID-19 cases (relative risk [RR], 1.24; 95% confidence interval [CI], 1.17 to 1.33) and deaths (RR, 1.18; 95% CI, 1.00 to 1.40) than other counties.

The authors noted that about 91% of counties with high proportions of black residents are in the South and that such counties have a higher prevalence of underlying illnesses, more air pollution, fewer healthcare resources, and higher proportions of uninsured, unemployed, and senior residents than other counties.

"We will continue to fail to address longstanding inequities until we commit to eliminating structural racism and the systemic roots that maintain and even reinforce these injustices," the authors wrote.
May 14 Ann Epidemiol study

Study finds obesity, poverty, increased COVID-19 risk in UK

Today in the Lancet Infectious Diseases, British researchers identified several risk factors associated with a positive COVID-19 test, including being male, being obese, living in poverty, and having chronic kidney disease.

The observational study, based in the UK, included 3,802 people tested for SARS-CoV-2, the virus that causes COVID-19, yielding 587 positive cases identified through electronic health records from Jan 28 through Apr 4.

Men ages 40 to 64 were more likely to test positive for COVID-19 (18.5%, 243 out of 1,316 people) compared to 13.3% (291 of 2,190) of women. Among 499 children ages 0 to 17 tested, only 4.6% had positive test results. Of 207 people with chronic kidney disease, 32.9% (68) tested positive, compared with 14.4% (519/3,595) without kidney disease. While 20.9% of obese people tested positive (142/680), compared with 13.2% (171/1,296) of people of healthy weight.

People living in urban versus rural settings and those living in poverty were also more likely to test positive for the novel coronavirus.

In an accompanying commentary, Rachel E. Jordan, PhD, and Peymane Adab, MD, MPH, both from the University of Birmingham write, "…the COVID-19 pandemic exacerbates existing socioeconomic inequalities, and this needs both exploration and mitigation in the coming months and years. As the UK prepares to loosen lockdown measures, knowing who is most at risk of infection is vital. This study highlights the more susceptible subgroups among those with relevant symptoms, although we cannot be sure why they are more susceptible."
May 15 Lancet Infect Dis study
May 15 Lancet Infect Dis commentary

CDC adds 3 novel flu viruses to risk assessment list

For the first time in 2 years, the US Centers for Disease Control and Prevention (CDC) has added novel flu viruses to its Influenza Risk Assessment Tool (IRAT). The addition of 3 new viruses raises the total to 19. The overall risks for all 3 were moderate, to varying degrees.

With IRAT, the CDC uses two criteria sets to assess the risk of novel viruses, one that focuses on potential human-to-human spread and the other on the overall public health impact. The additions were first reported by Avian Flu Diary (AFD), an infectious disease news blog.

Two of the additions are North American lineage swine influenza variants, one an H3N2 strain detected in US residents in 2016 and 2017 and the other an H1N2 variant linked to 13 infections in the United States in summer 2018. The third is an H9N2 avian influenza strain from China linked to seven illnesses in 2018, mainly in people exposed to poultry.
May 11 CDC summary of IRAT results
May 17 AFD post

Last Ebola patient discharged in remaining DRC hot spot

The last Ebola patient in a recent outbreak of the disease in the Democratic Republic of the Congo (DRC) has been released from the treatment center in Beni, the World Health Organization (WHO) African regional office said late last week on Twitter.

No new cases have been reported since the end of April, following a cluster of seven cases. In a May 14 update, the WHO said one patient was still in the community in an unsecured area. As of May 12, 90 contacts were still under surveillance, including 41 who had high-risk contact with body fluids of the last confirmed case, though all have passed the high-risk 7- to 13-day period. So far, 37 of the 41 high-risk patients have been vaccinated, and since Apr 10, health workers have vaccinated 1,486 people in the area where the cluster emerged.

The outbreak total stands at 3,462 cases, 2,279 of them fatal, according to the WHO, which added that the cluster highlights the importance of heightened vigilance and that investigation will continue into the recent transmission chain.
May 15 WHO African regional office tweet
May 14 WHO update