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9780521704632c22 CUFX213A/Peck 9780521618168 December 29, 2007 14:51
22 Antimicrobials(P.aeruginosa)tends to be sensitive but resistance is acquired rapidly if used in
isolation.Ciprofloxacinis the most commonly employed drug in this group and is
active against a wide range of gram-negative and some gram-positive bacteria (strep-
tococcus and enterococcus have moderate sensitivity).Norfloxacinis only available
as an oral preparation for uncomplicated urinary tract infections andLevofloxacin
has increased pneumococcal cover that lends itself for use in lower respiratory tract
infections.Ofloxacinis more potent against both gram-negative and gram-positive
organisms and has acquired less resistance. It is also indicated in lower respiratory
tract infection as well as urinary sepsis.
Ciprofloxacin is also used as a first line treatment for anthrax infection and must
be administered with rifampicin or clindamycin when infection is suspected. Peni-
cillins and cephalosporins are not indicated if the potential for molecular biological
manipulation of the presenting strain exists. Pneumonic plague also has bioterrorism
potential and ciprofloxacin is similarly recommended as first-line treatment. Vac-
cines are available for both these conditions.Mechanism of action
The quinolones are bactericidal antimicrobials that inhibit theαsubunit of the DNA-
gyrase enzyme. This enzyme is responsible for the negative supercoiling of bacterial
DNA and when inactivated rapidly results in cell death.Kinetics
Quinolones are well absorbed from the gut although this is reduced in the presence of
magnesium, calcium/iron salts and sucralfate. They are widely distributed and have
excellent CSF and tissue penetration. Protein binding lies between 15–40%. They
undergo limited metabolism (active metabolites), and excretion is via urine and
faeces mainly in the unchanged form (60–80% of ofloxacin is excreted in the urine).
Dose reduction is only required in severe renal impairment and ciprofloxacin dose
adjustment is unnecessary when patients are on CVVHDF.Side effects
Central nervous system – it should be used with caution in epileptic patients and
it may cause restlessness, confusion and seizures.
Gut–nausea, vomiting and abdominal pain can all occur.
Haematological – haemolytic reactions can occur in patients with defects of glucose
6-phosphate dehydrogenase.
Interactions – the half-life of concurrently administered theophylline is increased.
Itis recommended that where concurrent administration is necessary theophylline
levels are measured.
Allergic reactions and transiently altered liver function have been reported.