Developments in Glycopeptide Antibiotics
Year: 2018
Type: article
Abstract: Glycopeptide antibiotics (GPAs) are a key weapon in the fight against drug resistant bacteria, with vancomycin still a mainstream therapy against serious Gram-positive infections more than 50 years after it was first introduced. New, more potent semisynthetic derivatives that have entered the clinic, such as dalbavancin and oritavancin, have superior pharmacokinetic and target engagement profiles that enable successful treatment of vancomycin-resistant infections. In the face of resistance development, with multidrug resistant (MDR) S. pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA) together causing 20-fold more infections than all MDR Gram-negative infections combined, further improvements are desirable to ensure the Gram-positive armamentarium is adequately maintained for future generations. A range of modified glycopeptides has been generated in the past decade via total syntheses, semisynthetic modifications of natural products, or biological engineering. Several of these have undergone extensive characterization with demonstrated in vivo efficacy, good PK/PD profiles, and no reported preclinical toxicity; some may be suitable for formal preclinical development. The natural product monobactam, cephalosporin, and β-lactam antibiotics all spawned multiple generations of commercially and clinically successful semisynthetic derivatives. Similarly, next-generation glycopeptides are now technically well positioned to advance to the clinic, if sufficient funding and market support returns to antibiotic development.
Source: ACS Infectious Diseases
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Awards: Potent Lipoglycopeptide Antibiotics Against C. Difficile, New antibiotics and treatment methods against drug-resistant bacteria, Novel membrane-targeted antibiotics against drug-resistant Gram-positive bacterial infections, Vancomycin Derived Drugs, Membrane-targeted antibiotic for complicated skin and skin structure (cSSSI) infections caused by MRSA, VISA and VRE (methicillin and Vancomycin-resistant S. aureus and enterococci)., G5099006245, Membrane-targeted antibiotic for complicated skin and skin structure (cSSSI) infections caused by MRSA, VISA and VRE (methicillin and Vancomycin-resistant S. aureus and enterococci)., Understanding how antibiotics work in order to design better ones
OpenAlex ID: W2785104789