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

Abstract

Risk factors predisposing to auditory toxicity of aminoglycosides were analyzed from records of 187 patients enrolled in three prospective randomized trials comparing the toxicity of netilmicin, tobramycin, and amikacin. Patients were eligible if they received three or more days of therapy and at least two serial audiograms were available. The overall auditory toxicity rate was 9.6% (18 of 187). Auditory toxicity was detected in 4.4, 10.8, and 23.5% of patients given netilmicin, tobramycin, and amikacin, respectively (P = 0.05). In the univariate analysis, patients who developed auditory toxicity were significantly older (P = 0.01) and had a significantly higher (P = 0.04) percentage of trough levels of netilmicin or tobramycin above 2 mg/liter or amikacin above 5 mg/liter. In the final logistic regression model, only age was retained as independently influencing the development of auditory toxicity (P < 0.00001). Conversely, factors that did not add significantly to the prediction of auditory toxicity were aminoglycoside serum levels, total aminoglycoside dose, duration of therapy, sex, peak temperature, presence of bacteremia, shock, liver cirrhosis, dehydration, previous otic pathology or renal failure, and development of renal toxicity. At least in certain populations, age is the most important predisposing factor for the development of auditory toxicity in patients receiving aminoglycosides.

Detecção precoce de ototoxicidade usando emissões otoacústicas produtivas de distorção

“…O critério usado para determinar alteração auditiva por ototoxicidade foi um incremento igual ou maior que 15 dB NA no limiar audiométrico, em uma ou mais freqüências. Este é um critério para ototoxicidade aceito por vários autores na literatura revisada 3,5,17,21 . Previamente às testagem das EOA-PD, os pacientes foram interrogados em relação à presença de hipoacusia, acúfenos e vertigem como manifestações de ototoxicidade, e foi realizada otoscopia na investigação de alterações sugestivas de patologia de ouvido médio.…”

“…Durante o tratamento, os testes foram feitos nos últimos quatro dias da administração da droga, no vale (antes da dose seguinte) e no pico sérico da amicacina (uma hora após administração) 5,12,17 . Finalmente, os pacientes foram testados 15 dias depois de terminado o tratamento.…”

Clinical Issues Surrounding Once‐Daily Aminoglycoside Dosing in Children

“…43 Data were collected on peak and trough serum drug concentrations, total dose, duration of therapy, age, and other factors. After logistic regression, only older age was a significant risk factor for this side effect.…”

Aminoglycoside-induced hearing loss in humans

“…Most studies consider ototoxicity to have occurred if at any time after a base-line audiogram has been obtained an increase occurs in the auditory threshold of 15 dB or more at any two frequencies (38,45,52,53,55,58,61,72) or 20 dB at one or more frequencies (5, 21,25,27). Some investigators consider a 15-dB or greater change at any frequency to represent ototoxicity (4, 29,40,50,76,[80][81][82][83]94), and others use some combination of criteria (10,32,33,66). The basis for accepting a 15-dB change in threshold as a meaningful change is that it is standard procedure to use 5-dB steps in sound intensity when obtaining auditory thresholds.…”