Evaluation of four once-daily aminoglycoside dosing nomograms

Study Objective. To evaluate the accuracy of four once-daily aminoglycoside dosing nomograms in producing the desired gentamicin peak concentration (C-max) target of 20 mug/ml in patients with varying degrees of renal function. Design. Retrospective analysis using prospectively collected pharmacokinetic data. Setting. Rural teaching hospital. Patients. Ninety patients receiving intravenous gentamicin divided into three groups (30 patients each) determined by estimated renal function: group 1, creatinine clearance (Cl-cr) 60 ml/minute or greater; group 2, Cl-cr 40-59 ml/minute; group 3, Cl-cr 20-39 ml/minute. Intervention. Serum gentamicin concentrations were collected for a 2-point (two consecutive infusions and one predose and one postdose concentration sampled during steady state) or 3-point (single infusion and one predose and two postdose concentrations at least 1.5 estimated half-lives apart) pharmacokinetic study for determination of patient-specific pharmacokinetic parameters (elimination rate constant, volume of distribution at steady state, and clearance) after 30-minute infusions of gentamicin 2.8 +/- 1.6 mg/kg. Measurements and Results. The four nomograms evaluated were from Hartford Hospital, Barnes-Jewish Hospital, University of Rochester, and the Sanford Guide. With a pharmacokinetic analysis program and the patient-specific pharmacokinetic parameters, C-max and minimum concentration (C-min) were determined with use of the recommended doses and dosing intervals of the four nomograms. Also, the gentamicin dose and interval needed to achieve a C-max and C-min of 20 mug/ml and 0.2 mug/ml, respectively, were determined. Dosing was based on total body weight unless that weight was more than 25% of ideal body weight, in which case, an adjusted body weight was used. In general, the recommended dosages and resultant C-max produced by the nomograms were significantly less (p<0.05) than the dosage and C-max actually needed to achieve a C-max:minimum inhibitory concentration (MIC) ratio of 10 or greater for bacteria with an MIC of 2 μg/ml. Conclusion. Once-daily aminoglycoside dosing using the four nomograms resulted in inaccurate dosing, and because of the large variability in human pharmacokinetics, dosing nomograms such as these should be abandoned in favor of individualizing dosages with therapeutic drug monitoring.