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一项关于新生儿万古霉素相关性肾毒性的倾向匹配队列研究。

A propensity-matched cohort study of vancomycin-associated nephrotoxicity in neonates.

作者信息

Constance Jonathan E, Balch Alfred H, Stockmann Chris, Linakis Matthew W, Korgenski E Kent, Roberts Jessica K, Ward Robert M, Sherwin Catherine M T, Spigarelli Michael G

机构信息

Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.

Pediatric Clinical Program, Intermountain Healthcare, Salt Lake City, Utah, USA.

出版信息

Arch Dis Child Fetal Neonatal Ed. 2016 May;101(3):F236-43. doi: 10.1136/archdischild-2015-308459. Epub 2015 Sep 23.

Abstract

BACKGROUND

The incidence of nephrotoxicity among vancomycin-treated neonates has been reported to range from 2% to 20%. These widely varying estimates have led to confusion and controversy regarding the safety of vancomycin among neonates.

OBJECTIVE

Evaluate the incidence of nephrotoxicity among neonates receiving vancomycin concomitantly with gentamicin.

DESIGN

Retrospective observational cohort study using propensity score matching to provide covariate balance between neonates who did or did not receive vancomycin based on factors known to be related to the development of renal dysfunction.

SETTING

Hospitals (n=22) throughout the Intermountain West, including a quaternary care children's hospital.

PATIENTS

Neonates ≤44 postmenstrual weeks (median gestational age: 31 (IQR 28-36) weeks) receiving intravenous gentamicin with or without exposure to vancomycin from January 2006 to December 2012.

MAIN OUTCOME MEASURES

Nephrotoxicity based on the modified Acute Kidney Injury Network criteria for acute kidney injury (AKI) or serum creatinine concentration ≥1.5 mg/dL persisting for ≥48 h.

RESULTS

The final cohort was comprised of 1066 neonates (533 receiving vancomycin and gentamicin vs 533 receiving gentamicin). In a propensity score-matched cohort that was well balanced across 16 covariates, AKI was not associated with vancomycin use (16 neonates receiving vancomycin vs 7 controls experienced AKI; OR 1.5; 95% CI 0.6 to 4.0). However, the presence of a patent ductus arteriosus, concomitant non-steroidal anti-inflammatory drug use, ≥1 positive blood cultures, low birth weight and higher severity of illness and risk of mortality scores were associated with an increased risk of nephrotoxicity.

CONCLUSIONS

These results corroborate several earlier reports and much anecdotal evidence describing the infrequent occurrence of nephrotoxicity in neonates receiving concomitant vancomycin and gentamicin.

摘要

背景

据报道,接受万古霉素治疗的新生儿中肾毒性的发生率在2%至20%之间。这些差异很大的估计导致了关于万古霉素在新生儿中安全性的困惑和争议。

目的

评估同时接受万古霉素和庆大霉素治疗的新生儿中肾毒性的发生率。

设计

回顾性观察队列研究,使用倾向评分匹配法,根据已知与肾功能障碍发展相关的因素,在接受或未接受万古霉素治疗的新生儿之间实现协变量平衡。

地点

整个美国西部山间地区的医院(共22家),包括一家四级护理儿童医院。

患者

2006年1月至2012年12月期间,胎龄≤44周(中位胎龄:31(四分位间距28 - 36)周)的新生儿,接受静脉注射庆大霉素,无论是否接触过万古霉素。

主要观察指标

根据改良的急性肾损伤网络(Acute Kidney Injury Network,AKI)急性肾损伤标准或血清肌酐浓度≥1.5 mg/dL持续≥48小时来判定肾毒性。

结果

最终队列包括1066名新生儿(533名接受万古霉素和庆大霉素治疗,533名仅接受庆大霉素治疗)。在一个在16个协变量上平衡良好的倾向评分匹配队列中,急性肾损伤与万古霉素的使用无关(16名接受万古霉素治疗的新生儿发生急性肾损伤,7名对照新生儿发生急性肾损伤;比值比1.5;95%置信区间0.6至4.0)。然而,动脉导管未闭、同时使用非甾体抗炎药、≥1次血培养阳性、低出生体重以及更高的疾病严重程度和死亡风险评分与肾毒性风险增加相关。

结论

这些结果证实了几份早期报告以及许多轶事证据,这些报告和证据描述了接受万古霉素和庆大霉素联合治疗的新生儿中肾毒性发生率较低的情况。

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