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