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Ciprofloxacin
Levofloxacin
Mechanism of action
- inhibit bacterial DNA gyrase (main target in gram -ve bacteria) and
topoisomerase IV (main target in gram +ve bacteria)
- although this major mechanism of action requires cell division quinolones
also have other mechanisms of action which result in them being active against bacteria that are not actively replicating
- cross outer membrane of gram -ve bacteria via porins
- affinity for bacterial target enzymes is 1000 times that for equivalent
human enzymes
- minimum inhibitory concentration (MIC) is increased in the presence of
magnesium and in acid environments (pH <6)
Resistance
- mutation of target enzymes
- porin impermeability
- efflux of drug
Affect all fluoroquinolones although some compounds may remain active against
resistant strains due to higher intrinsic activity
Pharmacodynamics
- concentration dependent killing
- ratio of area under the concentration-time curve to MIC is thought to
be the factor most closely related to clinical efficacy
- exert a post-antibiotic effect. Duration depends on pathogen, drug
concentration and period of exposure to drug
Adverse effects
- GI complaints: nausea, vomiting, abdominal pain
- CNS: headaches, vertigo, tremors, fits
- may exacerbate myasthenia gravis
- interferes with development of cartilage in experimental animals and
therefore not recommended in children, and pregnant and lactating women
- leucopaenia, anaemia, eosinophilia, thrombocytosis
- increased transaminases and creatinine
Drug interactions
| Drug |
Effect |
| Aluminium and magnesium containing antacids, sucralfate ±
Zn, Fe and Ca salts |
Decrease absorption of quinolones from GI tract |
| Xanthines |
Quinolones interfere with metabolism resulting in higher
blood concentrations of theophylline and
other xanthines. Effect is absent with ofloxacin and norfloxacin |
| Probenicid |
Blocks renal tubular secretion of quinolones |
| ß lactams |
Sometimes synergistic |
| Chloramphenicol, rifampicin, nitrofurantoin |
Antagonistic (except with ciprofloxacin, ofloxacin) |
| Cyclosporin |
Moderate reduction in clearance of cyclosporin |
Pharmacokinetics
- admin PO/IV. All fluoroquinolones well absorbed from GI tract except in the
critically ill, in whom studies of bioavailability have had differing results.
Therefore it seems sensible to administer ciprofloxacin intravenously in this
group.
- distribution: all have high volumes of distribution and penetrate
intracellularly (thus reach important intracellular organisms such as Legionella,
Chlamydia and Mycobacteria. Concentrated in alveolar lining fluid
- elimination: approximately 30% metabolized in the liver, 60% excreted in the
urine (20% as metabolites) and 15% in bile
Spectrum of activity
Sensitive micro-organisms include:
- enterobacteria
- Pseudomonas aeruginosa
- Acinetobacter
- Haemophilus spp.
- methicillin-sensitive Staph. aureus
- Neisseria spp.
- Legionella
- Brucella spp.
- Bordatella spp.
- Corynebacterium spp.
Bacteria with intermediate sensitivity include:
- Streptococcus spp.
- Mycoplasma spp.
- Chlamydia spp.
- Rickettsia spp.
- M. tuberculosis
Resistant bacteria include:
S-enantisomer of ofloxacin
Pharmacokinetics
- administration: PO or IV. There are currently no published data on
levofloxacin absorption in the critically ill. Absorption in healthy
volunteers is good but is reduced by concomitant adminstration of antacids,
divalent cations (may be in NG feed) and sucralfate (if administered within
2 hours)
- elimination: 80% excreted by kidneys unchanged. Dosage should be decreased
in patients with significant renal dysfunction
- Cmax and AUC are at least as high following IV adminstration to critically
ill patients as they are in healthy volunteers suggesting that no change in
dosing is necessary.
Spectrum of activity
Similar to ciprofloxacin but greater activity against pneumococcus and
methicillin sensitive Staph. aureus. Whether levofloxacin is less active
than ciprofloxacin against Pseudomonas aeruginosa is controversial.
Further reading
Rovold KA, Neuhauser M. Pharmacokinetics and pharmacodynamics
of fluoroquinolones. Pharmacotherapy 2001;21:233S-252S
Van Bambeke F. Mechanisms of action. In Armstrong D, Cohen J.
Infectious diseases. Mosby, London, 1999, pp7/1.1-7/1.14
Potential conflict of interest
The Dept of Anaesthesia & Intensive Care, The Chinese
University of Hong Kong received funding for research on levofloxacin from
Daiichi Pharmaceuticals in 2002 and 2003
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