High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections -: Efficacy and toxicity
High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections -: Efficacy and toxicity
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DOI：
10.1001/archinte.166.19.2138
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发表时间：
2006-10-23
影响因子：
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通讯作者：
Wong-Beringer, Annie
中科院分区：
文献类型：
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作者：
Hidayat, Levita K.;Hsu, Donald I.;Wong-Beringer, Annie
背景：最低抑菌浓度(MIC)较高的耐甲氧西林金黄色葡萄球菌(MRSA)耐药株感染的万古霉素治疗失败，最近的指南建议较高的万古霉素靶向浓度为15~20微克/毫升。方法：对感染MRSA的成人患者进行前瞻性队列研究，以确定万古霉素MIC的分布和以至少4倍MIC为目标的万古霉素剂量的治疗效果。微生物学实验室计算机记录被用来识别从2004年8月1日至2005年6月30日期间分离出MRSA的所有患者。主要观察指标为临床反应、死亡率和肾毒性。结果：95例患者中，51例(54%)感染高MIC菌株，合并肺炎(77%)和/或菌血症。无论MIC如何，如果达到目标低谷，初步应答率为74%。然而，尽管达到了目标低谷，与低MIC组相比，高MIC组的治疗结束反应(24/39[62%]比34/40[85%]；P=.02)和感染相关死亡率(11/51[24%]比4/44[10%]；P=.16)更高。在多因素分析中，高MIC(P=.03)和急性生理学和慢性健康评估II评分(P=.009)是不良反应的独立预测因素。肾毒性仅发生在高谷组(11/63[12%])，与其他肾毒性药物联合治疗可显著预测肾毒性。结论：临床MRSA菌株中万古霉素MIC升高(2µg/m L)的高流行率要求积极的经验性万古霉素剂量以达到大于15 m u g/m L的低谷。对于由这些菌株引起的侵袭性感染，应考虑联合或替代治疗。
Background: Vancomycin hydrochloride treatment failure for infections caused by susceptible methicillin-resistant Staphylococcus aureus (MRSA) strains with high minimum inhibitory concentration (MIC) has prompted recent guidelines to recommend a higher vancomycin target trough of 15 to 20 mu g/mL.Methods: A prospective cohort study of adult patients infected with MRSA was performed to determine the distribution of vancomycin MIC and treatment outcomes with vancomycin doses targeting an unbound trough of at least 4 times the MIC. The microbiology laboratory computer records were used to identify all patients from whom MRSA was isolated from August 1, 2004, through June 30, 2005. Primary outcome measures were clinical response, mortality, and nephrotoxicity. Patients were placed into subgroups based on target trough attainment and high vs low vancomycin MIC (>= 2 vs < 2 mu g/mL) for efficacy and high vs low trough (>= 15 vs < 15 mu g/mL) for nephrotoxicity analyses.Results: Of the 95 patients in the study, 51 (54%) were infected with high-MIC strains and had pneumonia (77%) and/or bacteremia. An initial response rate of 74% was achieved if the target trough was attained irrespective of MIC. However, despite achieving the target trough, the high-MIC group had lower end-of-treatment responses (24/39 [62%] vs 34/40 [85%]; P=.02) and higher infection-related mortality (11/51 [24%] vs 4/44 [10%]; P=.16) compared with the low-MIC group. High MIC (P=.03) and Acute Physiology and Chronic Health Evaluation II score (P=.009) were independent predictors of poor response in multivariate analysis. Nephrotoxicity occurred only in the high-trough group (11/63 [12%]), significantly predicted by concomitant therapy with other nephrotoxic agents.Conclusions: High prevalence of clinical MRSA strains with elevated vancomycin MIC (2 mu g/mL) requires aggressive empirical vancomycin dosing to achieve a trough greater than 15 mu g/mL. Combination or alternative therapy should be considered for invasive infections caused by these strains.