Stewardship / Resistance Scan for Feb 03, 2021

News brief

CARB-X funds work on novel antibiotic for carbapenem-resistant pathogens

CARB-X announced today that it is awarding up to $6.4 million to French biopharmaceutical firm Mutabilis to develop a new class of antibiotics to treat infections caused by carbapenem-resistant Enterobacterales (CRE) bacteria.

The award from CARB-X (the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) will help fund the preclinical development of EBL-1463, a potential first in-class representative of the dabocin family. The compound is a non-beta-lactam inhibitor of penicillin-binding proteins that kills bacteria by interfering with cell wall synthesis. Lab testing has shown it to be impervious to any beta-lactamase-based resistance tested, which suggests it could be effective against CRE and other carbapenem-resistant bacteria.

"New treatments are urgently needed to address serious life-threatening antibiotic-resistant bacterial infections, like those caused by CRE and other Gram-negative bacteria for which there are few treatment options," CARB-X chief of research and development Erin Duffy, PhD, said in a CARB-X press release. "The novel inhibitor of penicillin-binding proteins designed and optimized by Mutabilis is an achievement in this area of antibacterial drug discovery."

Mutabilis, of Romainville, France, will be eligible for an additional $5.8 million if it meets certain project milestonest.
Feb 3 CARB-X press release

 

UK trials finds no benefit from azithromycin in hospital COVID-19 patients

New data from the United Kingdom's RECOVERY trial shows that azithromycin did not improve survival or other prespecified clinical outcomes in hospitalized COVID-19 patients, according to results published yesterday in The Lancet.

In the azithromycin arm of the randomized, controlled trial, which is being conducted in 176 UK hospitals to identify effective treatments for hospitalized COVID-19 patients, eligible patients were randomly allocated to receive either standard of care alone or standard of care plus 500 milligrams of oral or intravenous azithromycin for 10 days or until discharge. The primary outcome was 28-day all-cause mortality.

A total of 7,763 patients were included in the study from Apr 7 through Nov 27, 2020, with 2,582 in the azithromycin group and 5,181 receiving standard of care. Overall, 561 (22%) of patients treated with azithromycin and 1,162 (22%) of patients in the standard-of-care group died within 28 days (rate ratio [RR], 0.97; 95% confidence interval [CI], 0.87 to 1.07). Similar results were observed among prespecified subgroups. In addition, no significant difference was seen in the length of hospital stay (10 days versus 11 days) or the proportion of patients discharged from the hospital alive within 28 days (69% vs 68%, RR, 1.04; 95% CI, 0.98 to 1.10).

Among those not on ventilators at baseline, there was no significant difference in the proportion of patients meeting the composite end point of invasive mechanical ventilation or death (25% vs 26%, RR, 0.95; 95% CI, 0.87 to 1.03).

Although azithromycin has not been recommended for routine use in COVID-19 patients unless there is evidence of a bacterial superinfection, macrolide antibiotics like azithromycin have been proposed as a possible treatment for COVID-19 because of their immunomodulatory activity. Azithromycin has widely been used in hospitalized COVID-19 patients during the pandemic, particularly in combination with the antimalaria drug hydroxychloroquine. But this and other trials have indicated that neither drug provides a benefit.

"Azithromycin use in patients admitted to hospital with COVID-19 should be restricted to patients in whom there is a clear antimicrobial indication," the investigators wrote.
Feb 2 Lancet study

News Scan for Feb 03, 2021

News brief

Higher viral load associated with COVID-19 transmission risk

Higher viral loads of SARS-CoV-2, the virus that causes COVID-19, are associated with an increased risk of transmission, according to cohort study results from Catalonia, Spain, published yesterday in The Lancet Infectious Diseases,

Researchers found that the overall secondary attack rate was 16.6%, although they ranged from 12% when the index case had a viral load lower than 1·106 copies per milliliter (mL) to 24% when viral load was 1·1010 copies per mL or higher.

Viral loads are not a set value, but previous research has shown they peak around the time of symptom onset, notes a related commentary by Laura Cornelissen, MD, and Emmanuel André, MD, PhD, two Belgian infectious disease experts.

Ninety of the 282 index cases (31.9%) in the study had at least one transmission event. Secondary attack rates Of the transmission events, 90% occurred in clusters where the index case had a viral load of 5.1 log10 copies per mL or higher and 50% had a viral load of 8.8 log10 copies per mL or higher.

The researchers used the same population as a previous hydroxychloroquine COVID study, drawing viral loads and infection timelines from 282 non-hospitalized adults positive with COVID-19. Each adult had at least one close contact from Mar 17 to Apr 28, 2020. Increased risk was associated with household contacts (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.59 to 5.65) and contact age (per-year OR, 1.02; 95% CI, 1.01 to 1.04).

Duration between exposure and symptom onset was inversely associated with the index case's viral load, going from 7 days when infected by an initial viral load lower than 1 X 107 copies per mL to 5 days when the initial viral load was 1 X 109 copies per mL or higher. The index case's age, sex, respiratory symptoms (eg, coughing), and mask usage were not associated with risk transmission.

"Rather than questioning the usefulness of mask-wearing policies, these results underscore the necessity of a multi-layered comprehensive approach to infection prevention and control," Cornelissen and André write. They also expand on the researchers' idea of using viral load as a means for risk stratification, saying that to do so would necessitate polymerase chain reaction tests that are not only quantitative but also standardized.
Feb 2 Lancet Infect Dis study
Feb 2 Lancet Infect Dis commentary

 

Strict mitigations may have minimized COVID cases at YMCA camps

Out of 6,830 youth and staff, 19 primary COVID-19 infections (0.6%) were linked to 2 secondary infections (0.07% of 3,030 contacts) at 54 YMCA day camps over several months, reports a study today in Pediatrics.

While other summer camps have reported high transmission rates, the researchers say the YMCA's mitigations—and staff and youth adherence to them—may have helped keep COVID-19 attack rates low.

The YMCA camps were hosted across six counties in North Carolina over 133 days from March to August 2020. Mitigations included daily temperature checks, frequent hand washing, staff training, site cleaning, and mask usage indoors and whenever physical distancing wasn't possible (which, according to an internal June audit, was adhered to more than 95% of the time).

Cohorts were also used, with the average size being 20 youth and 6 staff across 5 days. Of those who got sick, 55% had fevers and 45% had coughs; hospitalization was not required.

The average age of youth and staff were 8.5 and 22 years, respectively.

While the researchers acknowledge the possibility of under-reported or undetected cases, their findings indicate that most primary cases were most likely products of community or household transmission.

"Although minority youth were more likely to attend indoor camps (where expected transmission risks may be increased)," they add, "we did not observe higher transmission rates in these settings. This finding may be particularly relevant to school and other congregate care settings where the majority of time has to be spent indoors due to weather or learning conditions."
Feb 3 Pediatrics study

 

Source unknown in E coli outbreak linked infections in 5 states

The US Centers for Disease Control and Prevention (CDC) said yesterday that an investigation is under way into the source of an Escherichia coli O157:H7 outbreak that has so far sickened 16 people in five states, 1 of them fatally.

Affected states are Washington, Oklahoma, Arkansas, Virginia, and New York. The first illness was reported on Dec 23, and the most recent symptom onset was Jan 7. Patient ages range from 10 to 95 years, and 88% are female.

Of 12 patients with available information, 9 were hospitalized. And of 11 people with more detailed status, 3 had hemolytic uremic syndrome, a potentially fatal kidney complication. The person who died was from Washington.

State and local health officials are interviewing people to see what they ate the week before they got sick. Health officials are using PulseNet, the national subtyping network, to find other illnesses that might be part of the outbreak.

Whole-genome sequencing suggests the E coli from sick people is closely related and that they were probably sickened by the same type of food. Sequencing also suggests that the outbreak strain has been linked in the past to a variety of sources, including romaine lettuce, ground beef, and recreational water.
Feb 2 CDC outbreak notice

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