Concentration-dependent killing with a post-antibiotic effect, allowing once daily dosing
Expansion
Pharmacodynamics
- Concentration dependent killing: the higher the peak relative to the MIC, the better the effect
- Post-antibiotic effect: suppression persists after levels fall
- Toxicity is trough dependent, from accumulation in renal tubular and cochlear cells
These properties justify once daily (extended interval) dosing: a high peak maximises killing while a long interval allows the trough to fall, minimising accumulation.
Toxicity
- Nephrotoxicity: usually reversible, non-oliguric
- Ototoxicity: cochlear and vestibular, and often irreversible
- Neuromuscular blockade, dangerous in myasthenia gravis
Monitoring: trough level before the next dose, with renal function, and audiometry for prolonged courses. Avoid concurrent nephrotoxins including NSAIDs, contrast, vancomycin and loop diuretics.
Avoid or adjust in renal impairment, the elderly, pregnancy and myasthenia gravis. They are typically used for short courses in Gram negative sepsis, and synergistically with a beta-lactam in endocarditis.
They are inactive against anaerobes because uptake requires oxygen-dependent transport.