University of Southern California, School of Pharmacy, Los Angeles, CA, USA.
Clin Ther. 2013 Jul;35(7):995-1004. doi: 10.1016/j.clinthera.2013.05.018. Epub 2013 Jul 2.
A subset of vancomycin-treated patients with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) developed persistent positive blood cultures. Treatment eventually failed.
A retrospective study was conducted to determine whether early response on day 3 after initiation of vancomycin therapy for MRSA BSI was associated with reduced rates of persistent bacteremia, end-of-treatment failure, and infection-related mortality. Patients' medical charts were reviewed. Susceptibility testing and molecular characterization of bacterial isolates were performed.
In this elderly cohort (n = 111; median age 70 years, interquartile range: 57-80 years), early response was observed in 62% of patients and was significantly (P < 0.0001) associated with lower rates of end-of-treatment failure (19% vs 57%) and infection-related death (1% vs 29%), but not with persistent bacteremia (17% vs 29%, P = 0.23). Nearly half (46%; 46 of 100 patients) remained on vancomycin therapy for the entire treatment course; those who continued despite lack of early response had a trend toward a higher risk of death than those who were switched to alternative therapy (38% vs 10%, P = NS). Most (68%) isolates had vancomycin MIC of >1 µg/mL, whereas 10% showed heterogeneous glycopeptide-intermediate Staph aureus (hGISA) phenotype. Nearly half (47%) were typed with staphylococcal cassette chromosome mec IV or V. In a multivariate logistic regression model, lack of response at day 3 was the strongest predictor for end-of-treatment failure, after adjustment for confounders such as age, Acute Physiology And Chronic Health Evaluation II score, intensive care unit admission, vancomycin MIC >1 µg/mL, unbound trough concentration <4 to 5× MIC, and continued vancomycin therapy without change.
Early response assessment after initiation of vancomycin therapy appeared to be useful for considering further diagnostic workup or a switch to alternative therapy to affect a positive outcome in patients with MRSA BSI.
在万古霉素治疗的耐甲氧西林金黄色葡萄球菌（MRSA）血流感染（BSI）患者亚群中，一些患者出现持续的血培养阳性。最终治疗失败。
进行了一项回顾性研究，以确定万古霉素治疗 MRSA BSI 后第 3 天的早期反应是否与降低持续性菌血症、治疗结束时失败和感染相关死亡率的发生率有关。回顾了患者的病历。进行了细菌分离株的药敏试验和分子特征分析。
在这个老年队列（n=111；中位年龄 70 岁，四分位距：57-80 岁）中，62%的患者观察到早期反应，且与较低的治疗结束时失败（19% vs 57%）和感染相关死亡率（1% vs 29%）发生率显著相关（P＜0.0001），但与持续性菌血症无关（17% vs 29%，P=0.23）。近一半（46%；100 名患者中的 46 名）在整个治疗过程中继续接受万古霉素治疗；那些尽管缺乏早期反应但仍继续治疗的患者比那些被转为替代治疗的患者死亡风险更高（38% vs 10%，P=NS）。大多数（68%）分离株的万古霉素 MIC＞1µg/mL，而 10%表现出异质性糖肽中介金黄色葡萄球菌（hGISA）表型。近一半（47%）的菌株类型为葡萄球菌盒染色体 mec IV 或 V。在多变量逻辑回归模型中，调整年龄、急性生理学和慢性健康评估 II 评分、入住重症监护病房、万古霉素 MIC＞1µg/mL、未结合谷浓度＜4 至 5×MIC 和未改变万古霉素治疗等混杂因素后，第 3 天无反应是治疗结束时失败的最强预测因素。
在万古霉素治疗开始后进行早期反应评估似乎可用于考虑进一步的诊断检查或转换为替代治疗，以影响 MRSA BSI 患者的阳性结果。
