Department of Paediatrics, University of Luebeck, University Hospital of Schleswig-Holstein, Luebeck, Germany.
Institute of Medical Biometry and Statistics, University of Luebeck, Luebeck, Germany.
J Antimicrob Chemother. 2020 Aug 1;75(8):2291-2298. doi: 10.1093/jac/dkaa156.
Vancomycin is an extensively used anti-infective drug in neonatal ICUs. However, exposure-toxicity relationships have not been clearly defined.
To evaluate the risk profile for hearing deficits in vancomycin-exposed very-low-birthweight infants (VLBWI).
In a large cohort study of the German Neonatal Network (GNN; n = 16 967 VLBWI) we assessed the association of vancomycin treatment and pathological hearing tests at discharge and at 5 year follow-up. We performed audits on vancomycin exposure, drug levels, dose adjustments and exposure to other ototoxic drugs in a subgroup of 1042 vancomycin-treated VLBWI.
In the GNN cohort, 28% (n = 4739) were exposed to IV vancomycin therapy. In multivariable logistic regression analysis, vancomycin exposure proved to be independently associated with pathological hearing test at discharge (OR 1.18, 95% CI 1.03-1.34, P = 0.016). Among vancomycin-treated infants, a cumulative vancomycin dose above the upper quartile (>314 mg/kg bodyweight) was associated with pathological hearing test at discharge (OR 2.1, 95% CI 1.21-3.64, P = 0.009), whereas a vancomycin cumulative dose below the upper quartile was associated with a reduced risk of pathological tone audiometry results at 5 years of age (OR 0.29, 95% CI 0.1-0.8, P = 0.02, n = 147).
Vancomycin exposure in VLBWI is associated with an increased, dose-dependent risk of pathological hearing test results at discharge and at 5 years of age. Prospective studies on long-term hearing impairment are needed.
万古霉素是新生儿 ICU 中广泛使用的抗感染药物。然而，暴露-毒性关系尚未明确界定。
评估接触万古霉素的极低出生体重儿（VLBWI）发生听力缺陷的风险特征。
在德国新生儿网络（GNN；n=16967 例 VLBWI）的一项大型队列研究中，我们评估了万古霉素治疗与出院时和 5 年随访时病理性听力测试之间的关联。我们对 1042 例接受万古霉素治疗的 VLBWI 进行了万古霉素暴露、药物水平、剂量调整和接触其他耳毒性药物的审核。
在 GNN 队列中，28%（n=4739）接受了 IV 万古霉素治疗。在多变量逻辑回归分析中，万古霉素暴露与出院时病理性听力测试独立相关（OR 1.18，95%CI 1.03-1.34，P=0.016）。在接受万古霉素治疗的婴儿中，累积万古霉素剂量高于四分位上限（>314mg/kg 体重）与出院时病理性听力测试相关（OR 2.1，95%CI 1.21-3.64，P=0.009），而累积万古霉素剂量低于四分位上限与 5 岁时病理性听阈结果的风险降低相关（OR 0.29，95%CI 0.1-0.8，P=0.02，n=147）。
VLBWI 接触万古霉素与出院时和 5 岁时病理性听力测试结果的增加、剂量依赖性风险相关。需要进行前瞻性研究以评估长期听力损伤。
