Stewardship / Resistance Scan for Apr 20, 2021

News brief

Rapid diagnostic for neonatal sepsis receives CARB-X funding

CARB-X announced today that it is awarding Durham, North Carolina, biotech company Baebies Inc. up to $3.9 million to develop a rapid, easy-to-use diagnostic test for sepsis in newborns.

The diagnostic platform the company is developing uses digital microfluidics technology to test a small blood sample for bacterial infection and return results within 15 minutes. The test will also be able to determine the pathogen causing the infection and its antibiotic susceptibility, and measure host response markers unique to neonatal populations.

The project is currently in the feasibility phase of development, and if it meets project milestones, Baebies will be eligible for an additional $7.7 million from CARB-X (the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator).

Sepsis is the body's overwhelming and often life-threatening response to an infection caused by bacteria. Neonatal sepsis kills up to 1.4 million infants worldwide each year, many in low- and middle-income nations with poor sanitation and limited healthcare resources.

"There is a critical need for a rapid and easy-to-use diagnostic platform for bacteremia—especially for the newborn population given the low circulating blood volume available for testing," Baebies Inc. co-founder and President Vamsee Pamula, PhD, said in a CARB-X press release. "Through this CARB-X partnership, the development of blood culture and identification of bacteria on our FINDER platform not only enables clinicians to receive results fast, but also conserves the limited blood volume by maximizing the diagnostic yield."
Apr 20 CARB-X press release

Studies show drop in fluoroquinolone use following FDA warning

Two new studies show that US use of oral fluoroquinolones dropped significantly after the Food and Drug Administration's (FDA's) 2016 safety warnings and label change.

Following a review of evidence linking fluoroquinolones to disabling and potentially permanent adverse effects involving tendons, muscles, joints, and the central nervous system, the FDA in May 2016 announced that it would remove indications for oral fluoroquinolones in acute, uncomplicate urinary tract infection (uUTI), acute sinusitis (AS), and acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). The impact to date of this label change on fluoroquinolone prescribing has been unclear.

To see whether the label change resulted in decreases in oral fluoroquinolone use, researchers from the University of Florida analyzed data from a nationally representative sample of privately insured patients before and after the label change.

In results published yesterday in JAMA Internal Medicine, the researchers found that, prior to the label change, fluoroquinolones were used in 41.6% of uUTI episodes, 31.9% of AE-COPD episodes, and 8.3% AS episodes, and trends in monthly fluoroquinolone prevalence were nearly flat. The month of the label changes (July 2016), they observed an immediate significant reduction for uUTI (-7.2%), and a smaller reduction for AS (-1.2%) and AE-COPD (-2.6%). Monthly declines continued thereafter.

At the end of the study period, fluoroquinolones were used in 19.2% of uUTI episodes, 14.6% of AE-COPD episodes, and 2.9% of AS episodes—pointing to some opportunities for improvement, the researchers concluded.
Apr 19 JAMA Internal Med abstract

In the other study, published yesterday in Antimicrobial Agents and Chemotherapy, researchers with the University of Pittsburgh School of Medicine and the VA Pittsburgh Healthcare System examined national prescription audit databases from August 2014 through February 2020 to explore the same issue.

They found that, from 2015 through 2019, fluoroquinolone fills decreased from 35,616,786 (111.1 per 1,000 persons) to 21,100,050 (64.3/1,000 persons) annually, with an annual decline of 10.8%. Ciprofloxacin, levofloxacin, and moxifloxacin fills fell annually by 10.4%, 11.2%, and 17.7%, respectively. Fills dropped significantly in May 2016 and continued to decrease significantly through June 2018. During the baseline period (August 2014 through April 2016), there was no significant change in monthly fluoroquinolone fills.

"Taken together, our data demonstrate national progress toward achieving stewardship goals for outpatient fluoroquinolones, and attest to the impact of FDA safety warnings in limiting use of these drugs," the authors wrote.
Apr 19 Antimicrob Agents Chemother abstract

News Scan for Apr 20, 2021

News brief

Study: ICU ECMO experience a factor in COVID-19 patient survival

An analysis of extracorporeal membrane oxygenation (ECMO) use at 17 intensive care units (ICUs) in the greater Paris area during France's first COVID-19 wave reveal that 90-day survival was strongly linked to a hospital's earlier experience with the procedure. Investigators from France detailed their findings yesterday in The Lancet Respiratory Medicine.

During France's first surge, clinicians in Paris organized ECMO indications and pooled resources, which consisted of six mobile ECMO teams to cover the region. For the study, the group looked at the outcomes of all 302 COVID-19 patients who received ECMO from Mar 8 through Jun 3, 2020, finding a survival rate of 46%.

The most common causes of death were multiorgan failure and septic shock. Factors independently associated with increased 90-day survival included treatment in centers that managed at least 30 ECMO cases a year. Others were shorter time between intubation and ECMO, younger age, and patients' higher pre-ECMO renal score. Investigators didn't see a difference between patients who had mobile or on-site ECMO.

In a related commentary, experts from the Netherlands and Germany wrote that the low survival rate in relative young people without severe underlying conditions is sobering and suggests that lung failure from SARS-CoV-2 is worse compared with other acute respiratory diseases. They also noted that ECMO complications in COVID-19 patients, especially intracranial hemorrhage and ventilator-associated pneumonia, was striking compared with other ECMO populations.

They conclude that regional cooperation like what occurred in Paris will continue to be needed, along with continued analysis of how to improve critical care treatment of the sickest patients. "Selection of appropriate patients remains highly important, especially in times of crisis when equipment might become scarce. Younger age, shorter time from intubation to ECMO, and absence of renal failure can improve outcomes."
Apr 19 Lancet Respir Med abstract
Apr 19 Lancet Respir Med commentary

More evidence that overweight, obesity is tied to severe COVID-19

Overweight and obese people are more likely to suffer severe symptoms of COVID-19 and require supplementary oxygen and invasive mechanical ventilation than healthy-weight peers, according to a new study in Diabetes Care that further spotlights these key risk factors.

But according to the study—based on 7,244 COVID-19 patients from 18 hospitals in 11 countries—being overweight or obese was not associated with an increased risk of death.

Among the patients, 34.8% were overweight and 30.8% were obese. The 65.6% patients who were obese and overweight were more likely to require oxygen or noninvasive ventilatory support (adjusted odds ratio [aOR], 1.44; 95% confidence interval [CI], 1.15 to 1.80) and invasive mechanical ventilatory support (aOR, 1.22; 95% CI, 1.03–1.46) than patients with normal body mass indexes (BMIs).

There was no association between overweight and in-hospital mortality (aOR, 0.88; 95% CI, 0.74–1.04), the authors said.

The results were similar to patients who had diabetes. The authors said about 90% of patients with type 2 diabetes are overweight or obese. The authors suggested that obese and overweight patients may experience higher levels of inflammation and more shortness of breath.

"Our findings highlight the importance of maintaining a healthy BMI, because patients with either overweight or obesity are at risk for severe COVID-19. Although reducing the current levels of overweight and obesity is unlikely in the short term to have an impact on the COVID-19 pandemic, doing so may contribute to reducing disease burden in future viral pandemics," the authors concluded.
Apr 15 Diabetes Care study

University of Minnesota researchers deploy novel field test for CWD

Researchers with the University of Minnesota have successfully deployed a novel, nanotechnology-based approach to field testing chronic wasting disease (CWD), according to a university press release.

The approach developed by the Minnesota Center for Prion Research (MNPRO) uses a technique known as RT-QuIC (real-time quaking-induced conversion) to identify CWD prions in deer tissue samples. The test, named MN-QuIC, generates a color change of red for positive CWD result and blue for negative, and uses field deployable equipment to garner results within 24 hours.

In a field test conducted in southeast Minnesota the week of Mar 8, the researchers obtained confirmation of misfolded prion proteins in tissue samples from CWD-positive white-tailed deer in just 9 hours with the test.

MNPRO researchers say the goal is a test that could be set up at individual testing stations statewide.

"This would help prevent CWD prions from entering our food supply and would be an important step forward in the fight against CWD," said Peter Larsen, PhD, co-director of MNPRO and an assistant professor at the University of Minnesota College of Veterinary Medicine.

CWD is a transmissible neurologic disease that produces small lesions in the brains of deer, elk, and other cervids. Though it is not yet known whether the disease can spread to humans, the Centers for Disease Control and Prevention recommends against eating meat from CWD-infected animals.

Larsen said MNPRO will continue to validate MN-QuIC over the coming months and plans additional field deployments in the fall.
Apr 19 University of Minnesota press release

WHO sees promising signs in malaria vaccine pilot program

In an update on a pilot program to vaccinate children in selected African countries with the RTS,S malaria vaccine, the World Health Organization (WHO) today said 1.7 million doses have been given in Ghana, Kenya, and Malawi, helping protect more than 650,000 children.

The RTS,S vaccine was developed by GlaxoSmithKline and has been shown to partially protect against Plasmodium falciparum in young children and cut levels of severe malaria, as well as severe anemia—the most common cause of death in children with the disease. The pilot program first launched in 2019 in Malawi, followed by rollouts in Kenya and Ghana.

In a statement, the WHO said the number of children immunized in a relatively short period underscores strong community demand and the capacity of countries to deliver the vaccine, which is given on a novel schedule of four doses before age 2.

Kate O'Brien, MD, the WHO's director of immunization, vaccines, and biologicals, said, "This vaccine may be key to making malaria prevention more equitable, and to saving more lives."

The WHO said it will use results from the pilot program to guide its recommendation for broader use of the vaccine across sub-Saharan Africa.
Apr 20 WHO statement
Apr 23, 2019, CIDRAP News story, "World's first malaria vaccine program launches in Malawi"