Cumulative and acute toxicity of repeated high-dose tobramycin treatment in cystic fibrosis.
Forty-six patients with cystic fibrosis and chronic bronchopulmonary Pseudomonas aeruginosa infection entered a study of tobramycin-related chronic and acute nephro- and acousticovestibular toxicity. The patients (mean age, 15.7 years) had previously received 2-week courses of tobramycin therapy, for a mean cumulative total of 279 days each. The cumulative tobramycin dose ranged from 632 to 7,644 mg/kg. The patients were studied before and at the end of a 2-week course of treatment with tobramycin (10 to 20 mg/kg per day) to discriminate between acute and chronic toxicity. In patients studied at the beginning of the present course of treatment, the glomerular filtration rate, measured as 24-h creatinine clearance, did not correlate with the cumulative dose of tobramycin received during previous courses. Eighteen patients (39%) had a reduced glomerular filtration rate compared with normal values (mean, 12.5% reduction) but normal serum creatinine values. Two patients (5%) had a high-frequency hearing deficit (above 8 kHz), but only one deficit was possibly related to tobramycin. No chronic vestibular toxicity was observed. During the course of treatment, no patients developed acute nephrotoxicity. After 2 weeks of treatment 32% had a slightly reduced hearing threshold (15 to 30 dB) in two or more high frequencies, and 28% had a fall in vestibular response greater than 25% of the initial value but remained within normal limits. Thus, the acute and chronic toxicity of repeated high-dose tobramycin treatment in cystic fibrosis patients seems to be very mild.
D000293:Adolescent; D000328:Adult; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced*; D007759:Labyrinth Diseases / Q000139:chemically induced*; D008297:Male; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000209:etiology; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000209:etiology; D014031:Tobramycin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
D014031:Tobramycin