Clinical use and toxicity of high-dose tobramycin in patients with pseudomonal endocarditis.

The effects and toxicity of tobramycin were assessed in 26 patients receiving high-dose (approximately 8 mg/kg/d) therapy for pseudomonal endocarditis or conventional-dose (approximately 3 mg/kg/d) therapy for various systemic Gram-negative infections. Patients in the high-dose group received an average of 29.5 g of drug over 49 days and the dosage was adjusted to maintain peak serum concentrations of 15-20 mg/l. In the conventional-dose group, patients received an average of 8.6 g of tobramycin over 26.7 days and the dosage was adjusted to achieve peak concentrations of 4-10 mg/l. Clinical evidence of acute renal failure was not apparent in any patient. Five of seven patients in the high-dose group, for whom audiologic data was available, exhibited loss of hearing sensitivity in the high frequency range, but no patients sustained significant reduction in hearing in the conversational frequency range. Patients receiving high-dose tobramycin do not appear to be at greater risk for development of nephrotoxicity than do patients receiving conventional-dose therapy.