Double-Blind Comparison of the Nephrotoxicity and Auditory Toxicity of Gentamicin and Tobramycin

Two hundred fifty-eight patients with suspected sepsis were treated with tobramycin or gentamicin in a prospective, randomized, double-blind trial. One hundred forty-six patients received nine or more doses, had serial determinations of serum creatinine, and were evaluated for nephrotoxicity; 91 were able to cooperate with audiometry and were evaluated for auditory toxicity. Auditory toxicity developed in five of 47 (10 per cent) given gentamicin and five of 44 (11 per cent) given tobramycin. Nephrotoxicity developed in 19 of 72 (26 per cent) given gentamicin and nine of 74 (12 per cent) given tobramycin (P<0.025). The severity of the nephrotoxicity was not different; the mean increase in creatinine was 1.3 mg per 100 ml (114.9 μmol per liter) in both groups. Both the tobramycin and gentamicin groups had a similar mean age, initial serum creatinine level, total dose, serum aminoglycoside level, and duration of therapy. We conclude that tobramycin causes nephrotoxicity less frequently than does gentamicin. NEPHROTOXICITY and ototoxicity are major factors limiting the clinical utility of aminoglycoside antibiotics. In laboratory animals, tobramycin is less nephrotoxic and less ototoxic than gentamicin.¹-⁶ Clinical studies have also suggested that tobramycin is less toxic than gentamicin.⁷-¹⁰ However, these studies have not conformed with methodologic standards for comparative drug trials.¹¹ For example, none has been randomized or double-blind, which means that bias may have influenced the results; in addition, most have included small numbers of patients. Because these clinical studies were inconclusive, we conducted a clinical trial to determine whether tobramycin causes less nephrotoxicity or less auditory toxicity.