The good news is that the U.S. FDA’s complete response letter (CRL) for Venatorx Pharmaceuticals Inc.’s intravenous antibiotic combination, cefepime-taniborbactam, in complicated urinary tract infections (cUTIs) requested no additional clinical testing. The bad news is the inevitable delay for a drug Venatorx and partner Melinta Therapeutics Inc. are aiming to position as a much-needed option for the fight against drug-resistant gram-negative infections.
Making them an antibiotic of last resort, the U.K.’s Medicines and Healthcare Products Regulatory Agency introduced new restrictions on the use of fluoroquinolones due to the risk of potentially long-term or irreversible side effects.
Researchers have identified a new class of antibiotics that works by blocking the transportation of lipopolysaccharide (LPS) to the outer membrane of the gram-negative bacterium Acinetobacter baumannii. The most advanced member of the class, zosurabalpin (RG-6006, Roche AG), was effective against multiple A. baumannii strains, including carbapenem-resistant and multidrug-resistant strains.
Researchers have used explainable artificial intelligence (explainable AI) to find structurally new antibiotics with minimal toxicity. They reported their findings online in Nature on Dec. 20, 2023. In animal testing, compounds identified via the method showed that they had activity against drug-resistant gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), one of the most serious bacterial public health threats.
The emergence of Staphylococcus aureus strains resistant to almost all approved antibiotics in the clinic poses an urgent public health concern. Thus, new antibiotics exploiting alternative antibacterial mechanisms or molecular structures are critically needed to address the long-term threat of multidrug-resistant S. aureus, particularly methicillin-resistant S. aureus (MRSA).
A newly discovered antibiotic has been shown to block the synthesis of bacterial cell walls via immutable targets, raising the prospect of a class of drugs that will not lose effect through the development of antimicrobial resistance. Clovibactin, isolated from soil bacteria, targets the cell wall precursor molecules lipid II, lipid III and undecaprenyl phosphate (C55PP), all of which have a pyrophosphate group in common.
A different class of antibiotics could ease the increasing resistance triggered by some gram-negative bacteria. LpxC inhibitors are not new, but all attempts to develop them have failed due to cardiovascular toxicity or ineffectiveness. A modification of the structure of these compounds may have solved the problem. Duke University scientists demonstrated the preclinical safety and efficacy of an LpxC inhibitor candidate against a wide selection of these pathogens.
A chance discovery has led to a new class of antibiotics with multiple arms that interacted with the cell wall of gram-positive bacteria, inhibiting their assembly and disarming them. “It was an accidental discovery. We were using it to stain cells. We also were running evaluations of antibiotics. One of my former students came to me and said: ‘I think we have discovered something that is quite potent as an antibiotic,’” the senior author Xingyu Jiang told BioWorld.
A week ahead of its May 29 PDUFA date, the U.S. FDA has approved Xacduro (sulbactam for injection; durlobactam for injection) for treating one of the toughest and most deadly infections, carbapenem-resistant Acinetobacter baumannii, in adults.
Researchers at NYU Langone Health and Janssen Biotech Inc. have reported on mAbtyrins, bioengineered molecules composed of human monoclonal antibodies and centyrins that are a new way to fight Staphylococcus aureus infection on all fronts.In their experiments, which were published in Cell Host & Microbe on April 24, 2023, the team described mAbtyrin, as “a protein-based therapeutic that targets 10 disease-causing mechanisms employed by S. aureus,” senior author Victor Torres told BioWorld.
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