Beta-lactams are antibiotics that have a beta-lactam ring nucleus. Subclasses include
All beta-lactams bind to and inactivate enzymes required for bacterial cell wall synthesis.
Beta-lactamases are enzymes produced by bacteria that break open the beta-lactam ring, inactivating the beta-lactam antibiotic. Some beta-lactamases are encoded on mobile genetic elements (eg, plasmids); others are encoded on chromosomes.
There are numerous different types of beta-lactamases. They are not all active against all beta-lactam antibiotics and so are broadly classified into several main groups based on their affinity for particular beta-lactams:
AmpC: Cephalosporins, cephamycins, monobactams, penicillins
Extended-spectrum beta-lactamases: Extended-spectrum penicillins (eg, piperacillin), most cephalosporins, monobactams
Metallo-beta-lactamases: Carbapenems plus all other beta-lactams, except the monobactam aztreonam (note, these enzymes are not inhibited by beta-lactamase inhibitors)
Penicillinases: Narrow-spectrum penicillins
Serine carbapenemases: Carbapenems plus all other beta-lactams
AmpC beta-lactamases are generally chromosomally encoded and commonly produced by Enterobacter, Serratia, Citrobacter, Providencia, Morganella, and Pseudomonas aeruginosa. AmpC production is variable and inducible by beta-lactam exposure, so some of these organisms may appear to be falsely susceptible to 3rd-generation cephalosporins by minimum inhibitory concentration (MIC) testing.
Extended-spectrum beta-lactamases (ESBLs) refer to a variety of plasmid-carried beta-lactamases produced by some Klebsiella species, Escherichia coli, and other Enterobacteriaceae.
Metallo-beta-lactamases can be chromosomally encoded in some organisms, such as Stenotrophomonas maltophilia, or can be acquired as can occur with a variety of gram-negative organisms including Klebsiella, Pseudomonas, and Acinetobacter.
Penicillinases are narrow-spectrum enzymes produced by a variety of organisms including staphylococci such as Staphylococcus aureus.
Serine carbapenemases, such as plasmid-mediated Klebsiella pneumoniae carbapenemase (KPC), are produced most often by K. pneumoniae but have also been reported among other Enterobacteriaceae.
Beta-lactamase inhibitors are drugs that block the activity of certain beta-lactamases and are thus sometimes combined with beta-lactam antibiotics. Examples include
Clavulanate, sulbactam, tazobactam: These drugs block penicillinases but not AmpC or carbapenemases. They also block some ESBLs in vitro, but most combinations that include these drugs are not reliable against ESBL producers clinically.
Avibactam, relebactam, vaborbactam: These drugs block ESBLs, most serine carbapenemases including KPC, and AmpC but not the metallo-beta-lactamases.
Avibactam: This drug also blocks some OXA carbapenemases.
There are no currently available beta-lactamase inhibitors active against metallo-beta-lactamases (MBLs), such as NDM-1 (New Delhi MBL-1), VIMs (Verona integron–encoded MBLs), and IMP (imipenem)-types, which can inactivate all beta-lactam antibiotics except for aztreonam. However, many strains that produce MBLs also produce other beta-lactamases that can hydrolyze aztreonam.
Drugs Mentioned In This Article
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