A nomogram for determining the appropriate dosing interval for the pulse dosing of aminoglycosides. The dashed curves depict the exponential decay of the aminoglycoside level following a 5 mg/kg dose (of gentamicin, netilmicin, or tobramycin) infused over one hour. The solid lines represent the corresponding linear regressions. The upper set is based on a creatinine clearance of 40 mL/min and the lower set is based on a creatinine clearance of 60 mL/min. A volume of distribution of 0.25 L/kg was assumed in both cases. The main objectives of the pulse dosing strategy are to: - achieve a high aminoglycoside peak (>10 x MIC) to maximize efficacy.
- allow a drug-free interval of 3 - 5 hours to minimize toxicity and permit the reversal of the adaptive post-exposure resistance.
If a dosing interval longer than 48 hours would be necessary to achieve the 2nd objective, then an alternative antimicrobial agent should be considered. Also, in patients with high clearance (e.g., young adults, cystic fibrosis, burns, etc) dosing intervals shorter than 24 hrs may be more appropriate. |