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静脉注射妥布霉素与多种抗假单胞菌抗生素联合用于囊性纤维化儿童的安全性。

Safety of intravenous tobramycin in combination with a variety of anti-pseudomonal antibiotics in children with cystic fibrosis.

作者信息

Deschamp Ashley R, Pettit Rebecca S, Donaldson Jennifer A, Slaven James E, Davis Stephanie D

机构信息

Pediatric Pulmonology, University of Nebraska Medical Center and Children's Hospital and Medical Center, Omaha, NE, USA.

Indiana University School of Medicine and Riley Hospital for Children at Indiana University Health, Indianapolis, IN, USA.

出版信息

SAGE Open Med. 2017 Oct 16;5:2050312117736694. doi: 10.1177/2050312117736694. eCollection 2017.

Abstract

OBJECTIVES

Previous studies have examined renal safety of once daily intravenous tobramycin in individuals with cystic fibrosis. This has been mainly in combination with ceftazidime in an adolescent or adult population. In this report, we describe our institutional experience of once daily intravenous tobramycin in combination with a variety of second anti-pseudomonal antibiotics in children with cystic fibrosis.

METHODS

We present a retrospective review including children with cystic fibrosis, who were admitted for a pulmonary exacerbation from January 2009 to December 2011, and treated using intravenous tobramycin. A literature review of once daily intravenous aminoglycoside dosing in cystic fibrosis was performed to compare our results to existing literature.

RESULTS

A total of 35 subjects were divided into once daily dosing (n = 20) versus multiple daily dosing (n = 15) groups. Mean age was 11.3 years (± 5.7) for the once daily dosing group and 13.1 years (± 4.4) for the multiple daily dosing group (p = 0.34). All subjects had normal baseline serum creatinine at admission (once daily dosing 0.49 ± 0.14 mg/dL vs multiple daily dosing 0.62 ± 0.23 mg/dL, p = 0.07). All subjects received intravenous tobramycin, and most received piperacillin-tazobactam as their second anti-pseudomonal antibiotic (once daily dosing 45% and multiple daily dosing 40%). There was no significant change in serum creatinine in either group during antibiotic treatment (once daily dosing 0.08 ± 0.12 mg/dL vs. multiple daily dosing 0.06 ± 0.10 mg/dL, p = 0.43). All subjects had significant improvement in lung function following intravenous antibiotic therapy.

CONCLUSION

We show that both once daily dosing and multiple daily dosing of intravenous tobramycin in combination with a variety of second anti-pseudomonal antibiotics were safe in terms of nephrotoxicity in children with cystic fibrosis. These findings are important given existing literature mainly examines once daily tobramycin in combination with ceftazidime, a cephalosporin, and the majority of our patients were on tobramycin with piperacillin-tazobactam, an extended spectrum penicillin plus beta-lactam. This contributes new information not previously examined in a pediatric cystic fibrosis population.

摘要

目的

既往研究已考察了每日一次静脉注射妥布霉素在囊性纤维化患者中的肾脏安全性。这主要是在青少年或成人人群中与头孢他啶联合使用。在本报告中,我们描述了我们机构在囊性纤维化儿童中每日一次静脉注射妥布霉素联合多种第二代抗假单胞菌抗生素的经验。

方法

我们进行了一项回顾性研究,纳入2009年1月至2011年12月因肺部加重住院并接受静脉注射妥布霉素治疗的囊性纤维化儿童。对囊性纤维化患者每日一次静脉注射氨基糖苷类药物的文献进行了综述,以将我们的结果与现有文献进行比较。

结果

共35名受试者被分为每日一次给药组(n = 20)和多次给药组(n = 15)。每日一次给药组的平均年龄为11.3岁(±5.7),多次给药组为13.1岁(±4.4)(p = 0.34)。所有受试者入院时基线血清肌酐均正常(每日一次给药组为0.49±0.14mg/dL,多次给药组为0.62±0.23mg/dL,p = 0.07)。所有受试者均接受静脉注射妥布霉素,大多数接受哌拉西林-他唑巴坦作为第二代抗假单胞菌抗生素(每日一次给药组为45%,多次给药组为40%)。抗生素治疗期间两组血清肌酐均无显著变化(每日一次给药组为0.08±0.12mg/dL,多次给药组为0.06±0.10mg/dL,p = 0.43)。所有受试者静脉抗生素治疗后肺功能均有显著改善。

结论

我们表明,在囊性纤维化儿童中,每日一次给药和多次给药的静脉注射妥布霉素联合多种第二代抗假单胞菌抗生素在肾毒性方面都是安全的。鉴于现有文献主要考察每日一次妥布霉素与头孢菌素头孢他啶联合使用,而我们的大多数患者使用的是妥布霉素与哌拉西林-他唑巴坦联合,后者是一种广谱青霉素加β-内酰胺,这些发现很重要。这提供了此前未在儿科囊性纤维化人群中考察过的新信息。

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本文引用的文献

1
Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: V. Aminoglycosides.
Pediatr Pulmonol. 2013 Nov;48(11):1047-61. doi: 10.1002/ppul.22813. Epub 2013 Sep 2.
2
Respiratory bacterial infections in cystic fibrosis.
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Once-daily versus multiple-daily dosing with intravenous aminoglycosides for cystic fibrosis.
Cochrane Database Syst Rev. 2012 Feb 15(2):CD002009. doi: 10.1002/14651858.CD002009.pub4.
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Curr Opin Pulm Med. 2010 Nov;16(6):604-10. doi: 10.1097/MCP.0b013e32833eebfd.
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