Comparison of the nephrotoxicity and auditory toxicity of tobramycin and amikacin

Abstract

A total of 157 patients were treated with tobramycin or amikacin in a controlled prospective randomized trial. Dosages were adjusted to renal function according to a nomogram. Trough and peak aminoglycoside levels were available at the end of the trial. Of the above total, 113 recipients of nine or more doses of tobramycin or six or more doses of amikacin, without other apparent cause of renal failure, were evaluated for nephrotoxicity. Thirty-six patients were evaluated for auditory toxicity. The patients in groups evaluated for either nephrotoxicity or auditory toxicity were similar with respect to intensity and etiology of bacterial disease, concurrent exposure to other antimicrobial drugs, a,ge and sex distribution, initial serum creatinine level, and total dose and duration of antimicrobial therapy. Nephrotoxicity of similar severity developed in 4 of 59 (6.8%) recipients of tobramycin and in 7 of 54 (13.1%o) recipients of amikacin (P > 0.05). Mild auditory toxicity developed in 3 of 19 (15.7%) recipients of tobramycin and in 2 of 17 (11.7%) recipients of amikacin (P > 0.05). When patients with abnormally high mean trough or peak aminoglycoside levels were excluded from comparison, nephrotoxicity was 6.12 and 5.12% (P > 0.05) and auditory toxicity was 17.6 and 7.69%6 (P > 0.05) in the groups given tobramycin and amikacin, respectively, We conclude that the nephrotoxicity and auditory toxicity of amniacin and tobramycin are not significantly different and that such toxicities are indeed infrequent events when the dosages of these drugs are adjusted to hold blood levels within the safe boundaries suggested by the studies of others.

Univariate and multivariate analyses of risk factors predisposing to auditory toxicity in patients receiving aminoglycosides

“…The aminoglycoside trials were designed to compare the toxicity of tobramycin and amikacin (trial 1) and tobramycin and netilmicin (trials 2 and 3). The details of trials 1 and 2 have been published (10,11). The design of trials 2 and 3 was exactly the same.…”

“…Low grades of a reversible glomerular nephrotoxicity and auditory toxicity are the major adverse effects associated with the administration of aminoglycosides (11,12,18,19,34,36). The frequency of auditory toxicity ranges from 2 to 44% (22,26,33,39), and although the auditory decrease most often is not very intense, in at least 50% of the cases, it is irreversible (24).…”

“…At least 5 to 15% of patients receiving netilmicin, tobramycin, or amikacin will develop an impairment in the glomerular function (11,12,18,19,34,36), most often reversible, and the percentage may be even higher among those receiving gentamicin (36). Ototoxicity, frequently irreversible, is the other major adverse effect of aminoglycosides (11,12,18,19,34,36). In the only published clinical study using a multivariate statistical approach (24), the overall rate of auditory toxicity in patients treated with gentamicin, tobramycin, or amikacin was 22.3%.…”

Basal Cochlear Lesions Result in Increased Amplitude of Otoacoustic Emissions

“…It is important to identify these effects at an early stage to prevent severe, long-term damage. Nephrotoxicity and ototoxicity are correlated with the increasing drug levels [1, 2, 3]and serum concentration of aminoglycoside [2, 4, 5, 6]. Ototoxicity is typically revealed by subjective symptoms such as dizziness, tinnitus, and hearing loss or by using objective measures of change to the auditory system such as electrocochleography and evoked response audiometry [7, 8].…”

Tobramycin and Amikacin Nephrotoxicity

“…Until recently, the clinical nephrotoxicity of amino glycosides has been compared using markers which ref lect the glomerular filtration rate [3,4,7,13,15,[22][23][24]33,34,43,44,46], Among them, serum creatinine is the simplest and most widely used [15,22,24,33,43,44]. Tubular markers such as beta-2-microglobulin (P2m) [5,14,21,36,[38][39][40] and other low molecular weight proteins [2,18,21,29,48], and brush border [9,10,28,48] and lysosomal enzymes [9,31,48] of the renal epithelial tubu lar cells are earlier and more sensitive [5,9,17,18,21,31,39,40], Their clinical usefulness, however, is not fully established [2,34,...…”