Pharmacology for Anaesthesia and Intensive Care

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Section IVOther important drugs

Monobactams

Aztreonam

Aztreonam is a synthetic monobactam antimicrobial that is potently active against

awide range of gram-negative bacteria only. It has no useful activity against gram-

positive or anaerobic organisms. Both Enterobacter and Pseudomonas are sensitive

although it is often combined with gentamicin when treating severe Pseudomonal

infections. It can be used in penicillin-allergic patients and has been used safely in

patients with known IgE antibodies to benzylpenicillin.

Pharmacokinetics

Aztreonam is a parenteral preparation with a plasma half-life of 1–2 hours. It only

has moderate CSF penetration and sputum penetration is poor (0.05%). Serous fluid

penetration is better with good penetration into synovial fluid and bone. It undergoes

minimal metabolism and is predominantly excreted unchanged in the urine. It can

be used in patients on CVVHDF but the dose must be decreased by 50–70% (same

dose interval.)

Side effects

Aztreonam is well tolerated but can cause an increase in bleeding time – INR and

APTT should be monitored during use. Reversible marrow suppression has been

reported as well as liver enzyme rises.

Macrolides

Macrolides have a range of activity similar to penicillin and may be used as alterna-

tive therapy in penicillin allergy. They cover most gram-positive organisms, Neisseria

and Haemophilus, with activity against gram-positive and gram-negative anaerobes.

However, they also have specific activity against Mycoplasma and Legionella for

which they are indicated.Erythromycinrepresents the parent member of this group

but more modern drugs are also now available.Clarithromycincauses less gastroin-

testinal upset and gives better cover against streptococci, Listeria and Legionella.

Azithromycinprovides better gram-negative cover (Branhamella catarrhalis,Neis-

seria andH. influenzaeMIC being up to 8 times lower), improved bioavailability and

longer half-life.

Mechanism of action

Macrolides are bactericidal or bacteriostatic depending on plasma concentration.

They halt bacterial protein synthesis by binding to the 50S ribosomal subunit after

formation of the initiation complex. Once bound the inhibition of translocation

occurs at the first step.