Gatell J M, Ferran F, Araujo V, Bonet M, Soriano E, Traserra J, SanMiguel J G
Infectious Diseases and Otorhinolaryngology Units, Hospital Clinic, Faculty of Medicine, Barcelona, Spain.
Antimicrob Agents Chemother. 1987 Sep;31(9):1383-7. doi: 10.1128/AAC.31.9.1383.
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 less than 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.
对参与三项前瞻性随机试验的187例患者的记录进行分析,以确定易导致氨基糖苷类药物耳毒性的危险因素。这三项试验比较了奈替米星、妥布霉素和阿米卡星的毒性。如果患者接受了三天或更长时间的治疗且至少有两次连续听力图,则符合入选标准。总体耳毒性发生率为9.6%(187例中有18例)。接受奈替米星、妥布霉素和阿米卡星治疗的患者中,耳毒性发生率分别为4.4%、10.8%和23.5%(P = 0.05)。单因素分析显示,发生耳毒性的患者年龄显著更大(P = 0.01),且奈替米星或妥布霉素谷浓度高于2毫克/升或阿米卡星谷浓度高于5毫克/升的百分比显著更高(P = 0.04)。在最终的逻辑回归模型中,只有年龄被保留为独立影响耳毒性发生的因素(P小于0.00001)。相反,对耳毒性预测没有显著增加作用的因素包括氨基糖苷类药物血清水平、氨基糖苷类药物总剂量、治疗持续时间、性别、最高体温、菌血症、休克、肝硬化、脱水、既往耳部病变或肾衰竭以及肾毒性的发生。至少在某些人群中,年龄是接受氨基糖苷类药物治疗的患者发生耳毒性的最重要易感因素。