Aminoglycoside dosing in renal transplant patients. Comparison of nomogram and individualized pharmacokinetic methods in patients with shifting renal function.

Serum amikacin concentrations were compared in infected renal transplant recipients that were compared in infected renal transplant recipients that were dosed using a creatinine-based nomogram (group I) or an individual computer-assisted pharmacokinetic dosing method (group II). A total of 30 treatment courses were administered. Mean postinfusion peak levels were 22 microgram/ml in group I and 23.4 microgram/ml in group II. Mean serum trough levels were 8.8 microgram/ml and 5.5 microgram/ml in groups I and II, respectively. Both peak and trough serum levels were significantly more often in the acceptable therapeutic (peak 20-32 microgram/ml) and nontoxic (through less than 10 microgram/ml) ranges in group 11 patients. Seventy-seven per cent of group II and 38% of group I peak levels were in the therapeutic range, while 87% of group II and 70% of group I trough levels were less than 10 microgram/ml. Ototoxicity developed with similar frequency in both groups and occurred significantly more often with a peak level greater than 32 microgram/ml. Declining renal function, usually as a result of allograft rejection, occurred in seven (44%) group I and only three (25%) group II patients but could not be exclusively related to amikacin in any patient. A serum trough level of greater than 10 microgram/ml was associated with an increased risk of declining renal function independent of other risk factors. Failures of aminoglycoside therapy are frequently associated with inadequate serum levels. Conversely, ototoxicity and nephrotoxicity may be related to elevated serum aminoglycoside concentrations. For these reasons, the computer-assisted pharmacokinetic dosing method should be used in septic surgical patients whose renal function is subject to sudden and unexpected changes.