Exploration of Once‐Daily Dosing of Aminoglycosides Through Bayesian Simulation

Study Objectives . To simulate peak and trough concentrations, using Bayesian forecasting, achieved with a variety of once‐daily dosing (ODD) regimens; to evaluate dosing regimens required to produce target peak and trough concentrations; to compare the peak‐to‐MIC (minimum inhibitory concentration) ratios and time above MIC for various dosing regimens and MICs; to stratify the information based on renal function estimates; and to use the results from these simulations to make recommendations regarding optimum ODD of aminoglycosides. Design . Simulation of ODD using a Bayesian technique and existing patient data. Setting . A tertiary referral, community teaching hospital. Patients . One hundred consecutive adults from the author's data base, with a wide variety of infections and underlying illnesses, who met strict inclusion criteria. Interventions . Two methods of dosing, weight‐based (4–7 mg/kg) and target concentration‐based (peak 10, 15, or 20 μg/ml, trough ≤ 0.3 μg/ml), were evaluated. Each patient had a known dosing‐sampling history, stable renal function, and at least two measured serum concentrations, and were being treated with either gentamicin or tobramycin. Measurements and Main Results . A wide range of peak and trough serum concentrations are achieved when dosages are chosen based on patient weight. Even with large dosages, some patients had very low peak‐to‐MIC ratios and time above the MIC, and vice versa. Variations in MIC had a much greater effect on dosing target values than did variations in dosage. A large degree of variability was also noted in doses and dosing intervals when using a target serum concentration approach. For both methods, an inverse relationship existed between calculated creatinine clearance and time above MIC, although there was little change over the range of 60–119 ml/minute. Conclusions . Bayesian simulation showed that weight‐based ODD of aminoglycosides did not produce clinically acceptable serum concentrations or target values in many patients. Young and elderly patients, and any patient with a creatinine clearance below 60 or above 119 ml/minute, are especially likely not to achieve an optimum serum concentration profile. Aminoglycoside ODD should be individualized by evaluating the peak‐to‐MIC ratio, time above MIC, and patient response.