ASP Scan (Weekly) for Sep 23, 2022

News brief

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

FDA advisers approve fecal transplant treatment for recurrent C difficile

Swiss biopharmaceutical company Ferring Pharmaceuticals announced yesterday that the Food and Drug Administration's (FDA's) Vaccine and Related Biologic Products Advisory Committee (VRBPAC) voted in favor of the company's investigational fecal microbiota transplant (FMT)-based therapy.

According to a company press release, VRBPAC voted 13 to 4 that the data from the biologics license application were adequate to support the effectiveness of RBX2660 (Rebyota) to reduce the recurrence of Clostridioides difficile infection (CDI) in adults following antibiotic treatment, and 12 to 1 that the data were adequate to support safety of the microbiota-based live therapeutic treatment, which is delivered via an enema.

FMT therapy involves transplanting beneficial bacteria into the gut of a patient with recurrent CDI, which is traditionally treated with antibiotics. FMT has been found in several studies to be an effective treatment for recurrent CDI, and the most recent treatment guidelines from the Infectious Diseases Society of America recommend it for patients who've had several bouts of recurrent CDI and have not been cured by antibiotics.

Up to 35% of CDI cases recur after initial diagnosis, and patients who have recurrent CDI have a significantly higher risk of further infection.

"Today's advisory committee vote represents an important milestone in Ferring's ongoing efforts to address the unmet need for interventions that can reduce the incidence of recurrent C. difficile infection, which represents a significant health burden for patients," Mirjam Mol-Arts, MD, executive vice president and chief medical officer of Ferring Pharmaceuticals, said in the release.

RBX2660 would be the first FMT therapy approved by the FDA.
Sep 22 Ferring Pharmaceuticals press release

 

Hemodialysis patients have fourfold higher C diff risk, study finds

A systematic review and meta-analysis found that chronic kidney disease patients who require maintenance hemodialysis (MHD) have a significantly increased risk of CDI compared to those who don't require MHD, researchers reported today in Infection Control & Hospital Epidemiology.

To evaluate the burden of and potential risk factors for CDI in MHD patients, who are known to be at increased risk for CDI because of substantial antibiotic exposure and frequent hospitalizations, Brown University researchers reviewed 240 studies published prior to March 2022; 15 of these studies provided data on CDI rates among people requiring MHD, and 8 of them also provided CDI rates among people not requiring MHD.

The pooled prevalence of CDI among persons requiring MHD was 19.14%, compared with 5.16% among persons not requiring MHD (odds ratio [OR], 4.35; 95% confidence interval [CI], 2.07 to 9.16). The linear increase in CDI over time for both groups was significant, increasing an average of 31.97% annually from 1993 to 2017 (OR, 1.32; 95% CI, 1.1 to 1.58). The linear annual increase was similar among persons requiring and not requiring MHD (OR, 1.28; 95% CI, 1.13 to 1.45).

Risk factors specific to the MHD population included being 65 years of age or older, serum albumin levels of 3 grams per deciliter or lower, higher Charlson comorbidity index scores, HIV, and bloodstream infections. Mortality associated with CDI was double among people requiring MHD, and the case-fatality rate ranged from 13.2% to 68.8%.

"The substantially higher and rising rates of CDI among persons requiring MHD and associated higher morbidity and mortality compared to persons not requiring MHD both emphasize the importance of preventing C. difficile spread and CDI in this patient population," the authors wrote.
Sep 23 Infect Control Hosp Epidemiol study

 

Spero, GSK to partner on oral carbapenem for complicated UTIs

Originally published by CIDRAP News Sep 22

Biopharmaceutical company Spero Therapeutics announced today that it has entered into a licensing agreement with GSK for the antibiotic tebipenem pivoxil hydrobromide (HBr).

Under the agreement, GSK will receive an exclusive license to develop and commercialize the novel oral carbapenem, which is being developed for treatment of complicated urinary tract infections, in all territories except Japan and certain other Asian countries.

"There is a high unmet medical need for a novel oral antibiotic as an alternative to intravenous hospital therapy for drug-resistant complicated urinary tract infections," Luke Miels, MBA, Chief Commercial Officer for GSK, said in a press release.

In April, the FDA told Spero that its review of the New Drug Application for tebipenem HBr had identified issues in the phase 3 trial results for the drug and that the data may not support approval. Following that meeting, the company announced that it was stopping all commercialization activities for tebipenem HBr and would reduce its workforce.

The FDA recently told Spero, however, that positive results from an additional phase 3 trial supported by confirmatory nonclinical evidence of efficacy could be sufficient to support approval. The company says it expects to start the trial in 2023.

"Spero's agreement with GSK provides a critical step towards fully realizing the value tebipenem HBr can potentially provide to physicians, payors, and patients," said Spero Chief Executive Officer Ankit Mahadevia, MD.
Sep 22 Spero Therapeutics press release
May 4 CIDRAP News scan

 

Scottish report shows no increase in healthcare-associated infections

Originally published by CIDRAP News Sep 21

A new report from Scotland's national health service shows that three key healthcare-associated infections remained stable or declined from 2020 to 2021.

Surveillance data compiled by Antimicrobial Resistance and Healthcare Associated Infection Scotland (ARHAIS) showed that despite an increase in the number of patients admitted to Scottish acute care hospitals in 2021 compared with 2020 and an increase in total occupied bed days, incidence of CDI and Staphylococcus aureus bacteremia (SAB) remained stable, at 20.8 and 29.1 per 100,000 population, respectively.

Incidence of healthcare-associated Escherichia coli bacteremia (ECB)—the most common cause of gram-negative bacteremia—fell by 6.4% from 2020 to 2021, to 37.1 per 100,000 bed-days.

Overall, non–COVID-19 healthcare outbreaks and incidents declined, from 136 in 2020 to 118 in 2021. The annual incidence of community-associated CDI, SAB, and ECB remained stable from 2020 to 2021.

ARHAIS also reports that it continues to review and develop guidance documents for the prevention and control of infections across all care settings. Surveillance priorities for 2022 include further investigation into the impact of the COVID-19 pandemic on healthcare-associated infections and the development of wider gram-negative bacteremia surveillance.
Sep 20 ARHAIS 2021 annual report

 

Survey finds physician empathy linked to lower antibiotic prescribing

Originally published by CIDRAP News Sep 21

A survey of general practitioners (GPs) in Denmark found that those who exhibited high levels of empathy had different antibiotic prescribing habits than low-empathy GPs, particularly when it comes to prescribing penicillins, researchers reported yesterday in BMC Primary Care.

The survey, sent to a stratified sample of 1,196 Danish GPs in 2016, included questions about demographic, professional, and antibiotic prescribing characteristics and used the Jefferson Scale of Empathy for Health Professionals to assess self-reported physician empathy. The high-empathy group was defined as GPs who had empathy scores above the 90th percentile, and the low-empathy group were those with scores below the 90th percentile. The response rate was 39%.

The results showed that 61% of GPs in the top decile of the empathy score were women. GPs in this decile reported the following person-centered factors as more important for their job satisfaction than the bottom decile: the patient-physician relationship, interaction with colleagues, and intellectual stimulation.

Overall, high-empathy scoring GPs had 19% fewer antibiotic prescriptions per year than the low-empathy group and prescribed significantly less penicillin (34% less) than the low-empathy GPs. This was true for most penicillin subcategories. The intra-profile variation index and confidence intervals showed less prescribing uncertainty among GPs with high empathy.

There were no significant differences in age, practice setting (urban vs rural), practice type (partnership vs solo), overall job satisfaction, or GP’s value of prestige and economic profit for their job satisfaction.

The authors say the findings suggest that high-empathy GPs may be more likely to spend time explaining to patients why they don't need an antibiotic rather than simply comply with the patient's request.

"Practitioners with a degree of empathy may prescribe less penicillin as they take better time to explain, meet the patient's fears and expectations, and evaluate antibiotic choice in their community with reference to local resistance patterns," the authors wrote. "A likely explanation may be that high empathy GPs better identify patient’s concerns and expectations and are able to contextualize the patient’s infection in the community."
Sep 20 BMC Prim Care study

Stewardship / Resistance Scan for Sep 23, 2022

News brief

FDA advisers approve fecal transplant treatment for recurrent C difficile

Swiss biopharmaceutical company Ferring Pharmaceuticals announced yesterday that the Food and Drug Administration's (FDA's) Vaccine and Related Biologic Products Advisory Committee (VRBPAC) voted in favor of the company's investigational fecal microbiota transplant (FMT)-based therapy.

According to a company press release, VRBPAC voted 13 to 4 that the data from the biologics license application were adequate to support the effectiveness of RBX2660 (Rebyota) to reduce the recurrence of Clostridioides difficile infection (CDI) in adults following antibiotic treatment, and 12 to 1 that the data were adequate to support safety of the microbiota-based live therapeutic treatment, which is delivered via an enema.

FMT therapy involves transplanting beneficial bacteria into the gut of a patient with recurrent CDI, which is traditionally treated with antibiotics. FMT has been found in several studies to be an effective treatment for recurrent CDI, and the most recent treatment guidelines from the Infectious Diseases Society of America recommend it for patients who've had several bouts of recurrent CDI and have not been cured by antibiotics.

Up to 35% of CDI cases recur after initial diagnosis, and patients who have recurrent CDI have a significantly higher risk of further infection.

"Today's advisory committee vote represents an important milestone in Ferring's ongoing efforts to address the unmet need for interventions that can reduce the incidence of recurrent C. difficile infection, which represents a significant health burden for patients," Mirjam Mol-Arts, MD, executive vice president and chief medical officer of Ferring Pharmaceuticals, said in the release.

RBX2660 would be the first FMT therapy approved by the FDA.
Sep 22 Ferring Pharmaceuticals press release

 

Hemodialysis patients have fourfold higher C diff risk, study finds

A systematic review and meta-analysis found that chronic kidney disease patients who require maintenance hemodialysis (MHD) have a significantly increased risk of CDI compared to those who don't require MHD, researchers reported today in Infection Control & Hospital Epidemiology.

To evaluate the burden of and potential risk factors for CDI in MHD patients, who are known to be at increased risk for CDI because of substantial antibiotic exposure and frequent hospitalizations, Brown University researchers reviewed 240 studies published prior to March 2022; 15 of these studies provided data on CDI rates among people requiring MHD, and 8 of them also provided CDI rates among people not requiring MHD.

The pooled prevalence of CDI among persons requiring MHD was 19.14%, compared with 5.16% among persons not requiring MHD (odds ratio [OR], 4.35; 95% confidence interval [CI], 2.07 to 9.16). The linear increase in CDI over time for both groups was significant, increasing an average of 31.97% annually from 1993 to 2017 (OR, 1.32; 95% CI, 1.1 to 1.58). The linear annual increase was similar among persons requiring and not requiring MHD (OR, 1.28; 95% CI, 1.13 to 1.45).

Risk factors specific to the MHD population included being 65 years of age or older, serum albumin levels of 3 grams per deciliter or lower, higher Charlson comorbidity index scores, HIV, and bloodstream infections. Mortality associated with CDI was double among people requiring MHD, and the case-fatality rate ranged from 13.2% to 68.8%.

"The substantially higher and rising rates of CDI among persons requiring MHD and associated higher morbidity and mortality compared to persons not requiring MHD both emphasize the importance of preventing C. difficile spread and CDI in this patient population," the authors wrote.
Sep 23 Infect Control Hosp Epidemiol study

News Scan for Sep 23, 2022

News brief

Risk of neurologic disorders in US veterans rose in year after COVID

The risk of a range of neurologic conditions rose significantly in the year after COVID-19 infection among a group of US veterans—regardless of whether they had required hospitalization, according to a study published yesterday in Nature Medicine.

Researchers at the Veterans Affairs St. Louis Healthcare System and Washington University used federal data to estimate the risk and incidence of new neurologic disorders in 154,068 COVID-19 survivors, 5,638,795 contemporary controls, and 5,859,621 prepandemic controls.

Most participants were White men, with an average age of 62 years. Most were unvaccinated because the study period, March 2020 to January 2021, predated wide vaccine availability. It also preceded the emergence of SARS-CoV-2 variants.

The researchers found a 42% increased risk of any neurologic condition, such as ischemic and hemorrhagic stroke (50% increase), cognitive and memory disorders (77%), epilepsy (80%), headache (35%), movement disorders (42%), and mental illness (43%).

COVID-19 patients also had 2 more cases Alzheimer's disease per 1,000 people than controls. "It's unlikely that someone who has had COVID-19 will just get Alzheimer's out of the blue," senior author Ziyad Al-Aly, MD, said in a Washington University press release. "But what we suspect is happening is that people who have a predisposition to Alzheimer's may be pushed over the edge by COVID, meaning they're on a faster track to develop the disease. It's rare but concerning."

Al-Aly said neurologic problems are developing in previously healthy COVID-19 patients and those with mild infections. "It doesn't matter if you are young or old, female or male, or what your race is," he said. "It doesn't matter if you smoked or not, or if you had other unhealthy habits or conditions."

Some neurologic conditions persist, while others resolve, in unknown proportions, Al-Aly noted. "Given the colossal scale of the pandemic, meeting these challenges requires urgent and coordinated—but, so far, absent—global, national and regional response strategies," he said.
Sep 22 Nat Med study
Sep 22 Washington University
press release

 

H1N2v flu infects Georgia swine handler and fairgoer

The US Centers for Disease Control and Prevention (CDC) today reported another variant H1N2 (H1N2v) flu infection, this time in a Georgia child. Like most of the other similar cases, the child had contact with pigs and had attended agricultural fairs before symptoms began.

Investigators found that the patient was not hospitalized and has since recovered. No respiratory illnesses had occurred in any household contacts, and no person-to-person H1N2v transmission was reported.

The illness raises the season's number of variant flu infections to eight from six states. Six involved H1N2v, and two were linked to H3N2v. In August, the CDC issued a health advisory that urged healthcare providers to monitor for variant flu infections and it said it expected more cases to surface during the ongoing agricultural fair season.
Sep 23 CDC FluView report

 

WHO experts advise 1 switch for next Southern Hemisphere flu vaccine

The World Health Organization (WHO) flu strain selection advisory group today announced the recommended strains for the Southern Hemisphere's 2023 flu season, which swaps out the H1N1 strain for both the egg- and cell-based vaccine versions.

For the upcoming year, the group recommended switching a virus similar to influenza A/Sydney/5/2021. The strain is different than the H1N1 strains included in the current Northern Hemisphere vaccines, which are A/Victoria/2570/2019 for egg-based vaccines and A/Wisconsin/588/2019 for cell-culture or recombinant vaccines.

In an accompanying Q and A, the WHO said flu virus detections, except for the influenza B Yamagata lineage, this year have returned to pre-COVID levels in many countries in the Southern Hemisphere, which provided the advisory group with enough viruses to support updated vaccine strain recommendations.
Sep 23 WHO recommendations
Sep 23 WHO Q and A

 

COVID-like virus in bats resistant to SARS-CoV-2 antibodies

A sarbecovirus found in Russian bats evades SARS-CoV-2 antibodies in people who have been vaccinated against COVID-19, according to a study yesterday in PLOS Pathogens.

The virus, Khosta-2, belongs to the same category of coronaviruses as the virus that causes COVID-19. It was identified in bats sampled near Sochi National Park in October 2020.

Researchers at the University of Washington, who conducted the study, said Khosta-2 would likely be able to infect humans, based on experiments using human cells from people vaccinated against SARS-CoV-2.

To conduct the study, the authors used sera from six vaccinated people (three Pfizer and three Moderna), four uninfected donors, and three vaccinated individuals with breakthrough infections through January of 2022. The authors infected the sera with Khosta-2 cells, and the virus was able to evade all antibodies to SARS-CoV-2. The virus was also able to evade monoclonal antibodies to SARS-CoV-2.

The primary mechanism of evasion was Khosta-2's spike protein, which attached to a receptor protein, called angiotensin converting enzyme 2 (ACE2.) The authors of the study said this should compel vaccine developers to consider making broader vaccines.

"Our research further demonstrates that sarbecoviruses circulating in wildlife outside of Asia—seven in places like western Russia where the Khosta-2 virus was found—also pose a threat to global health and ongoing vaccine campaigns against SARS-CoV-2," said Michael Letko, PhD a virologist and corresponding author of the study, in a University of Washington press release.
Sep 22 PLoS Pathog study
Sep 22 University of Washington press release

 

Six countries report new polio cases this week

According to the latest update from the Global Polio Eradication Initiative (GPEI), six countries have new polio cases this week.

Afghanistan, Pakistan, and Mozambique all have new wild poliovirus type 1 cases. This is Afghanistan's second case in 2022; last year the country reported 4 cases. In Pakistan, 2 polio cases were recorded, bringing the 2022 total to 19. In Mozambique, intensified surveillance has tracked 1 new polio case, bringing the yearly total to 6 in that country.

Benin and the Democratic Republic of the Congo reported cases of circulating vaccine-derived poliovirus type 2 (cVDPV2). Benin has 2 cases, with 6 total reported this year. The DRC has 1 case, but its 2022 total is 111, up from 28 cases in 2021.

Malawi has two circulating vaccine-derived poliovirus type 1 (cVDPV1) cases. These are the first reported in the country; last year one wild-type case was reported.
Sep 21 GPEI update

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