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Clinical use and toxicity of high-dose tobramycin in patients with pseudomonal endocarditis
Abstract:
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.
Insights
High-dose tobramycin for pseudomonal endocarditis showed no increased risk of kidney toxicity compared to conventional doses. Some high-frequency hearing loss occurred, but conversational hearing remained unaffected.
Area of Science:
- Pharmacology
- Nephrology
- Ototoxicology
Background:
- Tobramycin is an aminoglycoside antibiotic used for Gram-negative infections.
- Pseudomonal endocarditis requires aggressive treatment regimens.
Purpose of the Study:
- To evaluate the safety and toxicity of high-dose tobramycin therapy.
- Compare nephrotoxicity and ototoxicity between high-dose and conventional-dose tobramycin.
Main Methods:
- Retrospective analysis of 26 patients with pseudomonal endocarditis or Gram-negative infections.
- Dosage adjusted to achieve specific peak serum concentrations (15-20 mg/l for high-dose, 4-10 mg/l for conventional-dose).
- Assessment of renal function and audiologic data.
Main Results:
- No clinical evidence of acute renal failure in either group.
- Five of seven patients on high-dose tobramycin experienced high-frequency hearing loss.
- No significant reduction in conversational hearing range was observed.
Conclusions:
- High-dose tobramycin therapy does not appear to increase nephrotoxicity risk compared to conventional doses.
- High-dose tobramycin may cause high-frequency hearing sensitivity loss.
- Careful monitoring is advised for patients on high-dose tobramycin therapy.