BL-BLI combinations are referred to as β-lactam combination drugs by the Clinical Laboratory Standards Institute (CLSI). To evade the production of β-lactamases, β-lactamase inhibitors (BLIs) were discovered, and these molecules are given in combination with a partner BL, as most BLIs do not possess significant PBP inhibition on their own. Classes A, C, and D enzymes possess a nucleophilic serine residue that is required for BL hydrolysis class B enzymes are metallo-β-lactamases that require Zn 2+ for activity.
Based on their tertiary structures, four main groups of β-lactamases (classes A, B, C, and D) are circulating around the world. The most problematic and difficult-to-treat β-lactamase-producing Gram negatives include extended-spectrum β-lactamases (ESBL)-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae (CRE) that produce KPC- or OXA-48-like carbapenemases, Pseudomonas aeruginosa, and Acinetobacter spp. The most common BL resistance mechanism in Gram-negative bacteria is the production of β-lactamases or enzymes that hydrolyze the amide bond of β-lactams inactivating the antibiotic and its ability to inhibit PBPs. There are four major classes of BLs: penicillins, cephalosporins, monobactams, and carbapenems.
Their mechanism of action is to inhibit bacterial cell-wall synthesis by forming a stable adduct with the peptidase domain of penicillin-binding proteins (PBPs), thus stalling peptide crosslinking and resulting in cell death.
Β-Lactams (BLs) are the largest class of antibiotics.