Therapeutic Drug Monitoring of Aminoglycosides

- May 25, 2022

Aminoglycosides (gentamicin, tobramycin and amikacin) are bactericidal antibiotics used to treat infections caused by Gram-negative organisms. Therapeutic drug monitoring is recommended to ensure adequate dosing and prevent adverse effects such as nephrotoxicity and ototoxicity. Aminoglycosides demonstrate concentration-dependent bactericidal activity, which is optimal when the maximum concentration (Cmax) is ≥ 10 times the minimum inhibitory concentration (MIC) of the organism. A MIC of 1 mg/L can be assumed for most organisms; however, higher MICs (e.g. ≥ 2 mg/L) are common with Pseudomonas aeruginosa. These peak concentrations correspond to an area under the concentration-time curve (AUC24) of 70-100 mg/L.h for gentamicin and tobramycin. Prolonged high AUC24 and minimum concentrations (Cmin) are more likely to cause toxicity.

Pharmacokinetic/Pharmacodynamic Targets*
Gentamicin or tobramycin
AUC24: 70-100 mg/L.h
Cmax: 15-30 mg/L
Cmin: < 1 mg/L
Amikacin
AUC24: 160-200 mg/L.h
Cmax: 30-60 mg/L
Cmin: < 2 mg/L
*For adult patients receiving once daily dosing, and excluding those with endocarditis
  • Aim for a Cmax at the higher end of the range for infections caused by Pseudomonas aeruginosa, given that its MIC is likely > 1 mg/L.
  • Aminoglycosides concentrate in the urine at higher concentrations than in the plasma, so an AUC24 at the lower end of the range (e.g. 70 mg/L.h) is usually sufficient for a urinary tract infection.
  • Aim for a higher AUC24 (e.g. 80-100 mg/L.h) for more serious infections.
  • Giving a higher dose and extending the dose interval (e.g. to 48 hours) is sometimes needed to attain both the optimal Cmax and Cmin

For a comprehensive guide on therapeutic drug monitoring for both aminoglycosides and vancomycin see Training workbook for therapeutic drug monitoring of aminoglycosides and vancomycin 6th edition.pdf

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