aminoglycoside antibiotics

see also;

• antibiotics

• bactericidal group originally obtained from Streptomyces species
• ototoxic & nephrotoxic if high dose or prolonged use
• active mainly against enteric Gram -ve bacteria
• uses: septicaemia, endocarditis
  • eg. gentamicin, tobramycin, netilmicin
• topical agents (these also active against Gram +ves but not Strept)
  • eg. neomycin, framycetin, kanamycin
• anti-tuberculous:
  • eg. streptomycin

• Gentamicin:
  • wide Gram -ve spectrum incl. Pseudomonas aeruginosa
  • aminoglyc. of choice for most hosp. acquired aerobic Gram -ve sepsis
• Tobramycin:
  • marginally more antipseudomonal than gentamicin
  • restricted use & ? if suspected pseudomonal sepsis;
• Netilmicin:
  • more resistant to enzymatic degradation than genta/tobramycin
• Amikacin:
  • most resistant to enzymatic degradation - 20x more costly than gentamicin
  • reserved for resistant cases only
• Streptomycin:
  • available under SAS for Rx of TB.

• Recent studies seem to indicate benefit in single daily doses for following reasons:
  1. higher conc. result in more rapid & extensive killing
  2. selection of resistant mutants during Rx less likely with higher conc.
  3. produce signif. post-antibiotic growth suppression effects even after brief exposure
  4. efficacy determined by area-under-curve of drug exposure, not time conc.>MIC
  5. nephrotoxicity & renal accumulation reduced with higher doses administered daily.
• However, few studies using gentamicin or tobramycin & limited experience with pts with severe renal impairment (CRN > 300umol/L), febrile neutropenic sepsis, endocarditis or in paediatric pts. In addition, insufficient evidence for risks of ototoxicity.
• Thus, may be reasonable to use the following single daily doses in adult pts <80yrs old with normal & stable renal function who are likely to be Rx for short periods (<7days):
  • gentamicin 4-5mg/kg
  • netilmicin 4.5mg/kg
  • amikacin 15mg/kg
  • These doses should be given as a 30min infusion.
  • No need for peak levels but check trough levels at least once:
  • Troughs should be less than 0.5mg/L gentamicin & netilmicin, & <5mg/L amikacin.