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Stewardship / Resistance Scan for Feb 03, 2021
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