Therapeutic aminoglycoside monitoring in renal failure patients

In patients with normal renal function, defined peak (5-10 mg/L) and trough levels (less than 2 mg/L) for gentamicin, tobramicin, and netilmicin are considered therapeutic. Netilmicin peak and trough levels were investigated in 50 patients requiring hemodialysis due to acute (70%) or permanent (30%) renal failure. Netilmicin was given at a dosage interval of 24 h, with a loading dose on the first day (1.5 mg/kg) and a reduced daily maintenance dose (0.5 mg/kg) supplemented to the posthemodialysis dosage (1.3 mg/kg) after each hemodialysis. As compared with studies on patients not requiring hemodialysis, mortality (44%) was higher, mainly due to uncontrolled infection, whereas ototoxicity (17%) was not. Peak (5.9 +/- 1.7 mg/L) and trough plasma levels (3.0 +/- 0.9 mg/L) were significantly lower in patients who did not respond and died than were peak (8.2 +/- 2.5 mg/L) and trough (3.8 +/- 1.2 mg/L) levels in patients responding to aminoglycoside treatment. In renal failure patients, there is obviously not only the risk of overdosing and toxic side effects but also the risk of insufficient bactericidal effect as a result of underdosing. Consequently, by use of an aminoglycoside dosage similar to the present schedule, peak levels (5-10 mg/L) as desired in normal subjects but trough levels (2.5-5 mg/L) that are considerably higher than in normal subjects should be the target concentrations for patients with advanced renal failure.