Merck Manual

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Beta-Lactams

By

Brian J. Werth

, PharmD, University of Washington School of Pharmacy

Last full review/revision May 2020| Content last modified May 2020
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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

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.

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