BETA-LACTAMASE INHIBITORS (CLAVULANIC ACID, SULBACTAM, & TAZOBACTAM)

Introduction: These substances resemble β-lactam molecules, but they have very weak antibacterial action and therefore we are not classifying them as antibiotics in nature. They are potent inhibitors of many but not all bacterial β-lactamases and can protect hydrolyzable penicillins from inactivation by these enzymes. Beta-lactamase inhibitors are most active against Ambler class A β-lactamases (plasmid-encoded transposable element [TEM] β-lactamases in particular), such as those produced by staphylococci, H. influenzae, N. gonorrhoeae, salmonella, shigella, E. coli , and K. pneumoniae.

Spectrum of activity: They are not good inhibitors of class C β-lactamases, which typically are chromosomally encoded and inducible, produced by Enterobacter sp, Citrobacter sp, S. marcescens , and P. aeruginosa , but they do inhibit chromosomal β-lactamases of B. fragilis and M. catarrhalis . The three inhibitors differ slightly with respect to pharmacology, stability, potency, and activity, but these differences usually are of little therapeutic significance.

Formulations: Beta-lactamase inhibitors are available only in fixed combinations with specific penicillins. The antibacterial spectrum of the combination is determined by the companion penicillin, not the β-lactamase inhibitor. An inhibitor extends the spectrum of a penicillin provided that the inactivity of the penicillin is due to destruction by β-lactamase and that the inhibitor is active against the β-lactamase that is produced. Thus, ampicillin-sulbactam is active against β-lactamase-producing S. aureus and H. influenzae but not against serratia, which produces a β lactamase that is not inhibited by sulbactam.

Similarly, if a strain of P. aeruginosa is resistant to piperacillin, it is also resistant to piperacillin-tazobactam because tazobactam does not inhibit the chromosomal β-lactamase produced by P. aeruginosa. The indications for penicillin-β-lactamase inhibitor combinations are empirical therapy for infections caused by a wide range of potential pathogens in both immunocompromised and immunocompetent patients and treatment of mixed aerobic and anaerobic infections, such as intra-abdominal infections.

RELATED;

1.  PENICILLINS

2.  CEPHALOSPORINS

3.  PHARMACOLOGY AND THERAPEUTICS

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