Pharmacology for Anaesthesia and Intensive Care

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22 Antimicrobials

Kinetics

Macrolides can be administered orally or parenterally. Erythromycin does irritate

gastric mucosa and is also rapidly degraded in an acidic environment. CSF pen-

etration is non-therapeutic even with inflamed meninges, but sputum and lung

penetration is good. Protein binding is highly variable in this group with 70–90% of

erythromycin and 12% of azithromycin being bound. Macrolides tend to be metab-

olized and excreted mainly via the liver; however, 40% of clarithromycin and 15% of

erythromycin is excreted unchanged in the urine. Doses for both erythromycin and

clarithromycin should be halved in patients on CVVHDF (protein binding of these

drugs is saturable and they are not removed by dialysis) but dose adjustment for

azithromycin is not required.

Erythromycin inhibits hepatic cytochrome P4503A, which is responsible for the

metabolism of alfentanil and midazolam so that concurrent use leads to raised serum

levels of these drugs.

Side effects


Gut–nausea, vomiting and diarrhoea occur especially following intravenous injec-

tion due to a prokinetic effect. Various hepatic dysfunctions have been reported

but are usually reversible.


Cardiovascular – a prolonged QT interval is associated with erythromycin and

clarithromycin and may precipitate ventricular tachycardia or torsades de pointes

especially when taken with terfenadine.


Interactions – the actions of theophylline, warfarin and digoxin may all be aug-

mented when given with macrolides. Erythromycin should be avoided in por-

phyria.

Aminoglycosides

The aminoglycoside group contains a large number of naturally occurring and syn-

thetic drugs includinggentamicin,netilmicinandtobramycin.They cover a wide

range of gram-negative enterobacteria and have gram-positive cover that includes

staphylococci and to a limited extent streptococci. Aminoglycosides have no anaero-

bic activity but are synergistic withβ-lactams and vancomycin. They are large polar

molecules that need active transportation to gain entry into bacterial cells. This

transportation is inhibited by divalent cations (calcium and magnesium), acidosis

and low oxygen tensions. (Antimicrobial activity dramatically improves in urine if

pH is raised.) Streptomycin is active againstMycobacterium tuberculosisand is only

used in this setting. Neomycin is too toxic for systemic administration and may be

used orally for pre-operative bowel sterilization (not absorbed).

Mechanism of action

Aminoglycosides are bactericidal antimicrobials that block protein synthesis by

binding to the bacterial 30S ribosomal RNA subunit. Bacterial ribosomal RNA