71. Carbapenems, monobactams, beta lactamase inhibitors

Page created on September 23, 2019. Last updated on January 7, 2022 at 22:48


Carbapenems have the broadest antibacterial spectrum of all beta lactam antibiotics. They are effective against many Gram-positive, Gram-negative and anaerobes, but not MRSA or enterococci. The most important ones are imipenem, meropenem and ertapenem. Imipenem is combined with cilastatin, a drug which delays its metabolism.

Due to the potentially significant side effects these drugs are considered a “last resort”.

Mechanisms of resistance:

Carbapenems are not inactivated by beta-lactamases, but carbapenemases exists.

Pharmacokinetics and dosing:

Carbapenems have low oral bioavailability, so only parenteral formulations are available.

Imipenem is metabolized by an enzyme in the kidney called dipeptidase. Cilastatin is a dipeptidase inhibitor and therefore increases the half-life of imipenem. Other carbapenems are excreted unchanged by the kidneys.

Adverse effects:

These drugs, especially imipenem, lower the seizure threshold and can cause convulsions. Due to this they should be used with care in people with decreased renal function.

Other common side effects include hypersensitivity, GI symptoms and irritation at the site of infusion.


The only important monobactam is aztreonam. It’s composed of a monocyclic beta-lactam ring, which makes it different from other beta-lactams, which have dicyclic beta-lactam rings.

Monobactams are interesting as they are effective only against Gram-negatives aerobes like pseudomonas, N. meningitidis and H. influenzae. It has no action against Gram-positives or anaerobes.

Aztreonam only exists in IV formulation. It distributes well, enters the CNS and is eliminated by the kidneys.

Side effects are similar to those of other beta-lactam antibiotics. Cross-allergy with penicillins is very rare, but hypersensitivity reactions can occur.

Beta-lactamase inhibitors

Because beta-lactamase production is the predominant cause of clinically important resistance to beta-lactam antibiotics, sensitive antibiotics can be given together with beta-lactamase inhibitors. This prevents the antibiotics from being inactivated.

We divide them into two types: those that have a beta-lactam structure and those who don’t.

  • Beta-lactam structure
    • Clavulanate
    • Sulbactam
    • Tazobactam
  • Non-beta-lactam structure
    • Avibactam
    • Vaborbactam


Beta-lactamase inhibitorsAntibiotic combined with
Beta-lactam structure







Non-beta-lactam structure





Not all beta-lactamases are the same. Some bacteria have the beta-lactamase encoded on a plasmid (a piece of DNA in the cytoplasm, separate from the chromosomes) while some bacteria have it encoded in the chromosome, as an inducible gene. Different beta-lactamases produced by different bacteria have affinity against different antibiotics.

For example, the extended-spectrum beta-lactamases (ESBL) have a very broad spectrum and can inactivate penicillins, cephalosporins and aztreonam, but not carbapenems. For bacteria who produce ESBL, carbapenems are usually the only effective option.

Beta-lactamases that can inactivate carbapenems, so-called carbapenemases, exist. There are two major types, KPC and metallo-beta-lactamases.

Beta-lactamase inhibitors with beta-lactam structure:

Clavulanate, sulbactam and tazobactam irreversibly inactivate plasmid-encoded beta-lactamases, often found in Staphylococcus, Neisseria, E. Coli, Klebsiella, Salmonella and Shigella. They can’t inactivate chromosomal beta-lactamases or metallo-beta-lactamases.

Beta-lactamase inhibitors with non-beta-lactam structure:

Avibactam and vaborbactam have broader spectrum than the previously mentioned drugs. In addition to plasmid-encoded beta-lactamases they can also inactivate chromosomal beta-lactamases. They still cannot inactivate metallo-beta-lactamases, but they can inactivate KPC.

Beta-lactamase inhibitorsDrugsPlasmid beta-lactamasesChromosomal beta-lactamasesKPCMetallo-beta-lactamases

Beta-lactam structure

Clavulanate, sulbactam, tazobactamEffectiveIneffectiveIneffectiveIneffective
Non-beta-lactam structureAvibactam, vaborbactamEffectiveEffectiveEffective


2 thoughts on “71. Carbapenems, monobactams, beta lactamase inhibitors”

  1. Hei!

    If carbapenems are not inactivated by beta lactamases, why would you give vaborbactam with meropenem?

    1. Very good question! Appearently some enterobacteriae produce a carbapenemase called KPC, against which vaborbactam is effective. Appearently the story isn’t so black and white, and there are some carbapenemases which are not metallo-beta-lactamases.

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