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Section IVOther important drugsSide effects
Fusidic acid is well tolerated in general with occasional reports of rash or gastroin-
testinal symptoms. Rapid intravenous administration has been reported to cause
transient hypocalcaemia (buffer effect) and parenteral use has been associated with
abnormalities of liver function including jaundice. Thrombocytopenia is rare but
has been associated with use.Nitroimidazoles
Metronidazole
Metronidazole is a potent inhibitor of obligate anaerobes and protozoa (such as
trichomonas and entamba). Clostridia, Bacteroides,T.pallidumand Campylobacter
are all sensitive whilst anaerobic streptococci and lactobacilli are resistant. In spite
of extensive use worldwide, resistance remains rare and in some countries has been
shown to be undetectable.Mechanism of action
The precise mechanism of action is still unclear but metronidazole possesses a nitro-
group that becomes reduced (and charged) in anaerobic conditions. Such condi-
tions are evident in the intracellular compartment of anaerobic organisms where
the reduced nitro group becomes trapped by virtue of its charge. Bacterial DNA is
then known to undergo strand breakage (mechanism unclear) and cell death follows.Kinetics
Metronidazole does not bind to plasma proteins but is metabolized to active com-
pounds. A third of the drug is metabolized to a hydroxy metabolite that is only elim-
inated slowly from plasma. The drug distributes widely in CSF, cerebral abscesses,
prostate and pleural fluid. Seventy-five percent is excreted in urine (the majority in
an unchanged form) and the drug is removed by dialysis. Dose adjustment while on
CVVHDF is not required.Side effects
Metronidazole is well tolerated with nausea or a metallic taste being most commonly
described. Rare side effects include rashes, pancreatitis and peripheral neuropathy.
Itshould not be combined with alcohol as a severe disulfuram-like reaction with
flushing and hypotension will ensue.Antifungal drugs
Polyenes
The majority of agents in this large group have no clinical application as they
exhibit similar toxicity to mammalian and fungal cells. However, a small number of