Department of Pharmacy, Nationwide Children's Hospital, Columbus, Ohio, USA.
Clin Ther. 2013 Jun;35(6):772-9. doi: 10.1016/j.clinthera.2013.05.008.
Current guidelines for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia recommend targeting a vancomycin AUC24/MIC ≥400. Data on the association between AUC24/MIC and microbiological clearance in patients with concomitant MRSA bacteremia and MRSA osteomyelitis are limited.
The objective of this study is to evaluate the association between the vancomycin AUC24/MIC and time to microbiological clearance in patients with concomitant MRSA bacteremia and MRSA osteomyelitis.
Adult inpatients with concomitant MRSA bacteremia and MRSA osteomyelitis treated with vancomycin from January 1, 2007, through December 31, 2011, were evaluated. Classification and regression tree analysis was used to identify the AUC24/MIC associated with time to microbiological clearance.
Fifty-nine patients had complete data available for review and were included in the analysis. Classification and regression tree analysis identified an AUC/MIC of 293 as the breakpoint that provides the greatest difference in time to microbiological clearance. On univariate analysis, mean (SD) time to clearance was 2 days shorter when the AUC/MIC was >293 (4 [2] days vs 6 [3] days, P = 0.01). Mean (SD) infection-related length of stay was 13 (6) versus 18 (14) days in patients with an AUC24/MIC ratio >293 or ≤293, respectively (P = 0.25). In patients with an AUC24/MIC ≤293, 39% versus 17% (P = 0.09) had recurrent bacteremia and were readmitted compared with patients with an AUC/MIC >293. Only 9% were able to achieve an AUC24/MIC >293 when the vancomycin MIC was >1 μg/mL.
We observed a >2.5-fold increase in time to microbiological clearance in patients with concomitant MRSA bacteremia and MRSA osteomyelitis unable to achieve a vancomycin AUC24/MIC >293. A 5-day increase in hospital and infection-related length of stay was observed when this target was not achieved. Recurrence of bacteremia and hospital readmissions were higher in the cohort who did not achieve an AUC24/MIC >293. Only 9% of patients were able to achieve an AUC24/MIC >293 if the isolate MIC was >1 μg/mL. Trough concentration did not correlate with AUC24/MIC. In patients with concomitant MRSA bacteremia and MRSA osteomyelitis treated with vancomycin, stewardship programs should optimize pharmacodynamic parameters, specifically AUC24/MIC, or alternative therapies should be considered.
目前治疗耐甲氧西林金黄色葡萄球菌（MRSA）菌血症的指南建议目标是使万古霉素 AUC24/MIC 达到≥400。同时患有 MRSA 菌血症和 MRSA 骨髓炎的患者中 AUC24/MIC 与微生物清除率之间的相关性数据有限。
本研究旨在评估同时患有 MRSA 菌血症和 MRSA 骨髓炎的患者中万古霉素 AUC24/MIC 与微生物清除时间之间的关系。
评估了 2007 年 1 月 1 日至 2011 年 12 月 31 日期间接受万古霉素治疗的同时患有 MRSA 菌血症和 MRSA 骨髓炎的成年住院患者。采用分类回归树分析来确定 AUC24/MIC 与微生物清除时间之间的关系。
59 例患者有完整的数据可供回顾分析。分类回归树分析确定 AUC/MIC 为 293 是微生物清除时间差异最大的分界点。单变量分析显示，当 AUC/MIC 大于 293 时，清除时间平均缩短 2 天（4 [2] 天 vs 6 [3] 天，P=0.01）。AUC24/MIC 比值大于 293 或等于 293 的患者的感染相关住院时间分别为 13（6）天和 18（14）天（P=0.25）。在 AUC24/MIC 比值小于 293 的患者中，39%的患者与 AUC24/MIC 比值大于 293 的患者相比（P=0.09）出现复发性菌血症和再入院。当万古霉素 MIC 大于 1μg/ml 时，仅有 9%的患者能够达到 AUC24/MIC 大于 293。
我们观察到同时患有 MRSA 菌血症和 MRSA 骨髓炎且无法达到万古霉素 AUC24/MIC 大于 293 的患者，其微生物清除时间延长了 2.5 倍以上。如果未达到此目标，则观察到住院时间和感染相关住院时间增加了 5 天。未达到 AUC24/MIC 大于 293 的患者中，复发性菌血症和住院再入院的发生率更高。如果分离株 MIC 大于 1μg/ml，则仅有 9%的患者能够达到 AUC24/MIC 大于 293。AUC24/MIC 与谷浓度不相关。接受万古霉素治疗的同时患有 MRSA 菌血症和 MRSA 骨髓炎的患者，应优化药物动力学参数，特别是 AUC24/MIC，或考虑替代治疗。
