Although β-lactams have been the most effective class of antibacterial agents used in clinical practice for the past half century, their effectiveness on Gram-negative bacteria has been eroded due to the emergence and spread of β-lactamase enzymes that are not affected by currently marketed β-lactam/β-lactamase inhibitor combinations. Avibactam is a novel, covalent, non-β-lactam β-lactamase inh...

Antibiotic resistance being called as the ‘ticking time bomb’ of the 21 st century, as the antibiotic channel is losing sheen and is on a standstill due to lack of initiatives for new antibiotic development, and other novel solutions are required for its revival. Penicillin, the oldest among the antibiotics, obtained from the Penicillium mold, was one of the first antibiotics used to treat infe...

A series of clinical NDM-5-producing Escherichia coli isolates obtained from two surveillance networks for carbapenem-producing Enterobacterales 2018 to 2019, namely, Switzerland (NARA) and Germany (SurvCARE), were analyzed. The 33 E. highly resistant ?-lactams, including novel ?-lactam/?-lactamase inhibitor combinations (ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam), remai...

BACKGROUND The extensive use of the β-lactam antibiotics in hospitals and in the community has created major resistance problems which has led to increased morbidity, mortality and healthcare costs. The use of the β-lactamase inhibitors in combination with the β-lactam antibiotics is currently the most successful strategy used for circumventing the resistance mechanisms. OBJECTIVE To evaluate...

Most methicillin-resistant Staphylococcus aureus (MRSA) strains produce beta-lactamase. To determine whether this enzyme(s) is identical to one or more of the four beta-lactamases produced by methicillin-susceptible strains, the beta-lactamases of 50 MRSA isolates were typed by using substrate profile analysis. Forty type A, no type B, ten type C, and no type D beta-lactamase-producing strains ...

We have determined a 1.18 Å resolution X-ray crystal structure of a novel ruthenocenyle-6-aminopenicillinic acid in complex with CTX-M β-lactamase, showing unprecedented details of interactions between ruthenocene and protein. As the first product complex with an intact catalytic serine, the structure also offers insights into β-lactamase catalysis and inhibitor design.

Cefiderocol is a cephalosporin designed to treat multidrug-resistant Gram-negative infections. By forming chelated complex with ferric iron, cefiderocol transported into the periplasmic space via bacterial iron transport systems and primarily binds penicillin-binding protein 3 (PBP3) inhibit peptidoglycan synthesis. This mode of action results in having greater vitro activity against many bacil...

β-Lactamases inactivate β-lactam antibiotics by hydrolysis of their endocyclic β-lactam bond and are a major cause of antibiotic resistance in pathogenic bacteria. The zinc dependent metallo-β-lactamase enzymes are of particular concern since they are located on highly transmissible plasmids and have a broad spectrum of activity against almost all β-lactam antibiotics. We present here essential...