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目标更高的万古霉素谷浓度对匹配患者队列的临床结局和成本的影响。

Effects of targeting higher vancomycin trough levels on clinical outcomes and costs in a matched patient cohort.

机构信息

Anti-Infective Research Laboratory, Wayne State University, Detroit, Michigan 48201, USA.

出版信息

Pharmacotherapy. 2012 Mar;32(3):195-201. doi: 10.1002/j.1875-9114.2011.01017.x.

Abstract

STUDY OBJECTIVE

To compare clinical outcomes and costs in patients treated with the new vancomycin guidelines recommending goal serum trough concentrations of 15-20 mg/L versus patients treated with vancomycin doses targeting trough concentrations 5-20 mg/L prior to the new guidelines.

DESIGN

Retrospective quasi-experimental study.

SETTING

Urban level I trauma center.

PATIENTS

A total of 200 patients treated with vancomycin for at least 72 hours for confirmed, complicated methicillin-resistant Staphylococcus aureus (MRSA) bacteremia during one of two study phases relative to the implementation of the vancomycin dosing guidelines targeting serum trough concentrations of 15-20 mg/L: 2005-2007 (preperiod phase) and 2008-2010 (postperiod phase). One hundred patients in each phase were matched in a 1:1 ratio according to diagnosis, any concomitant nephrotoxic agents (e.g., aminoglycosides, colistin, acyclovir), and age ± 5 years.

MEASUREMENTS AND MAIN RESULTS

Patients in the preperiod had significantly lower success rates with vancomycin than those in the postperiod (45% vs 60%, p=0.034). Median length of stay (LOS) was not significantly higher in patients in the preperiod versus postperiod (15 days vs 13.5 days; p=0.28), and patients in the preperiod received a longer median duration of vancomycin versus those in the postperiod (13 days vs 8.5 days; p<0.001). No statistically significant difference was noted in total hospital costs for patients treated with vancomycin during the preperiod versus the postperiod ($32,754 vs $27,709, p=0.147). However, total drug and monitoring costs of vancomycin were significantly higher for patients in the postperiod. Initial vancomycin trough levels were significantly lower in patients in the preperiod versus postperiod (12.3 mg/L vs 15.8 mg/L, p=0.02). Patients in the preperiod had lower rates of nephrotoxicity than those in the postperiod, although this difference was not statistically significant (15% vs 18%; p=0.85). Median (interquartile range) LOS was significantly longer in patients who developed nephrotoxicity compared with patients who did not develop nephrotoxicity (17 days [11.5-36.5 days] vs 14 days [9-24 days], p=0.017). Costs associated with measurement of serum creatinine concentrations and vancomycin trough levels as well as labor were significantly higher in patients who developed nephrotoxicity.

CONCLUSION

Higher vancomycin trough concentrations improved outcomes in patients with complicated MRSA bacteremia. In addition, more aggressive dosing was shown to significantly decrease overall duration of vancomycin therapy, which may affect total hospital LOS and cost. Patients who experienced nephrotoxicity had a significantly longer hospital LOS. Additional studies evaluating optimal therapy for MRSA bacteremia in a larger cohort of matched patients are warranted.

摘要

研究目的

比较接受新万古霉素指南治疗的患者(目标血清谷浓度为 15-20mg/L)与接受新指南之前治疗的万古霉素剂量靶向谷浓度为 5-20mg/L 的患者的临床结局和成本。

设计

回顾性准实验研究。

地点

城市一级创伤中心。

患者

在两个研究阶段之一期间接受万古霉素治疗至少 72 小时的确诊、合并耐甲氧西林金黄色葡萄球菌(MRSA)菌血症的共 200 例患者,相对于万古霉素剂量靶向血清谷浓度为 15-20mg/L 的指南的实施:2005-2007 年(前期阶段)和 2008-2010 年(后期阶段)。每个阶段的 100 例患者按照诊断、任何伴随的肾毒性药物(例如氨基糖苷类、粘菌素、阿昔洛韦)和年龄±5 岁进行 1:1 匹配。

测量和主要结果

前期患者的万古霉素治疗成功率明显低于后期患者(45%比 60%,p=0.034)。前期患者的中位住院时间(LOS)与后期患者相比没有显著增加(15 天比 13.5 天;p=0.28),前期患者接受的万古霉素中位治疗时间明显长于后期患者(13 天比 8.5 天;p<0.001)。前期和后期接受万古霉素治疗的患者的总住院费用无统计学差异(32754 美元比 27709 美元,p=0.147)。然而,后期患者的万古霉素总药物和监测费用明显更高。前期患者的初始万古霉素谷浓度明显低于后期患者(12.3mg/L 比 15.8mg/L,p=0.02)。前期患者的肾毒性发生率低于后期患者,尽管这一差异无统计学意义(15%比 18%;p=0.85)。与未发生肾毒性的患者相比,发生肾毒性的患者的 LOS 中位数(四分位距)明显更长(17 天[11.5-36.5 天]比 14 天[9-24 天],p=0.017)。发生肾毒性的患者测量血清肌酐浓度和万古霉素谷浓度以及劳动力的相关成本明显更高。

结论

较高的万古霉素谷浓度可改善合并 MRSA 菌血症患者的结局。此外,更积极的剂量给药可显著缩短万古霉素治疗的总持续时间,这可能影响总住院 LOS 和成本。发生肾毒性的患者的住院时间明显更长。需要进一步研究评估更大队列匹配患者中治疗 MRSA 菌血症的最佳治疗方法。

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