Betalactamases

Enzyme systems which are able to hydrolytically split the betalactam ring of various antibiotics. This process causes the loss of the antimicrobial effect of the antibiotic in question. Among the betalactamases are penicillinase and cephalosporinases. ESBL (extended spectrum betalactamases) and carbopenemases have an extended spectrum of activity. The formation of the enzymes can only be induced by the antibiotic during therapy. However, this then takes place continuously and constitutively.

Among the betalactamases there is a variety of different classes and variants (>340). They are either chromosomally or plasmid-coded. Their chemical structure is different. Most betalactamases are serine betalactamases. They have a serine molecule in their active centre. Other rare betalactamases have a central zinc ion(metallobetalactamases).

Plasmid-coded betalactamases can have an extended spectrum of activity. This is especially true for the "extended spectrum betalactamases", ESBL, which by definition not only cleave aminobenzylpenicillins, ureidopenicillins and cephalosporins of the 1st and 2nd generation, but even those of the 3rd generation such as cefotaxime, ceftriaxone, ceftazidime. The carbapenems are stable compared to ESBL. ESBL formers are mainly found in Escherichia, Klebsiella and Proteus. Due to their chemical structure, > 2000 different ESBL can be distinguished (ELBL of the classes TEM, CTX-M, SHV, OXA).

Some Klebsiellen and Pseudomonaden have enzymes (carbapenemases e.g. OXA48 or NDM = New-Dehli-Metallocarbapenemase) with a further extended spectrum that exceeds the spectrum of ESBL. Some of these can cleave all betalactams.

There are clinically available inhibitors against individual beta-lactamases (beta-lactamase inhibitors = BLI). They are usually administered as a fixed combination (e.g. amoxicillin + clavulanic acid; ampicillin + sulbactam; piperacillin + tazobactam; ceftazidim + avibactam).

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