Gentamicin/Tobramycin
Class
Aminoglycoside
Dose
7mg/kg (sepsis)
4-6mg/kg (age/kidney fn as step down)
Mechanism
Bactericidal & Bacterostatic
Most Pr Synth Inhibitors are static, this one is both
MoA
- Enters bac via O2 dependant process
- Binds 30S ribosome
- Interferes w protein assembly (bacteriostatic)
- Disrupts cell memb (bactericidal)
Time v Conc
Concentration
Post Dose Effect
Long. Daily dosing. Even when no drug is detectable, exhibits strong inhibition of bacterial growth 2 strong irrev rib binding
SPectrum
Covers
Doesnt
- G- (most) including Pseudomonas, Enterobacter, Serratia, Morganella
- Anaerobic
- Gram +ves
- Atypicals
(limited synergistic role in some G+ve endocarditis Staph/Strep, although it results in quicker killing there is higher risk of renal impairment and no long term benefit)
Indications
- Sepsis
- Pseudomonas (Tobramycin preferred 1st line)
PK
A
Poor
D
Weak PPB, 0.3Lkg, Wide. Poor CNS/eye/CSF penetration
M
Not metabolised
E
Excreted in urine by glomerular filtration
AE
- Nephrotoxicity
- Exacerbated neuromuscular blockade & Myasethenia gravis
- Ototoxicity
- Auditory – idiosyncratic but profound
- Vestibular – delayed
Resistance
- Don’t fn well in anaerobic enviro (ie abscess)
- Poor chest penetrance
Monitoring
Peak levels correlate w efficacy
Trough levels indicate toxicity
Renal fn