Barlow Ashley, Heil Emily L, Claeys Kimberly C
University of Maryland Medical Center, Baltimore, MD, USA.
University of Maryland School of Pharmacy, Baltimore, MD, USA.
Infect Dis Ther. 2021 Mar;10(1):605-612. doi: 10.1007/s40121-021-00401-1. Epub 2021 Jan 23.
Vancomycin remains first-line therapy for methicillin-resistant Staphylococcus aureus (MRSA) blood stream infections (BSI); however, its toxicity and reported clinical failures are well established. Binary efficacy endpoints evaluating alternative anti-MRSA therapies leave clinicians deciphering between segregated clinical and safety outcomes and do not provide a comprehensive patient-centered picture of comparative therapies. This study aimed to apply a novel methodology, desirability of outcomes ranking (DOOR), to compare anti-MRSA therapies.
This was a single-centered, retrospective, cohort of adult patients with MRSA BSI that received vancomycin, daptomycin, or ceftaroline. A previously developed DOOR for S. aureus BSI was adjusted and applied to this cohort to compare vancomycin-treated versus daptomycin/ceftaroline-treated patients. The DOOR had five mutually exclusive ranks: (1) alive without treatment failure, infectious complications, or grade 4 adverse events (AEs); (2) alive with any one of treatment failure, infectious complications, or grade 4 AE; (3) alive with two of treatment failure, infectious complications, or grade 4 AE; (4) alive with all three treatment failure, infectious complications, or grade 4 AE; or (5) deceased.
A total of 43 vancomycin-treated and 13 daptomycin/ceftaroline-treated patients were included. Baseline clinical characteristics were similar, except for higher median serum creatinine in the daptomycin/ceftaroline cohort (0.76 [IQR 0.57, 1.11] vs 1.36 [IQR 1.09, 1.91] mg/dL, P = 0.03). Patients in the daptomycin/ceftaroline cohort had a 92% probability of better outcome using DOOR methodology. Patients treated with daptomycin/ceftaroline experienced less MRSA BSI persistence (0% vs 13.9%), MRSA BSI recurrence (7.8% vs 25.6%), grade 4 AEs (23.1% vs 46.5%), and in-hospital mortality (0% vs 9.3%).
Although limited by sample size, this study demonstrates the potential of DOOR to produce valuable, patient-centered results. Clinicians are encouraged to become familiar with appropriate use and interpretation of DOOR methodology as it will become an increasingly common endpoint in clinical trials.
万古霉素仍然是耐甲氧西林金黄色葡萄球菌（MRSA）血流感染（BSI）的一线治疗药物；然而，其毒性以及报道的临床治疗失败情况已得到充分证实。评估替代抗MRSA治疗方法的二元疗效终点使临床医生难以区分分离的临床和安全性结果，并且无法提供以患者为中心的全面的比较治疗情况。本研究旨在应用一种新方法，即结局期望排名（DOOR），来比较抗MRSA治疗方法。
这是一项单中心、回顾性队列研究，纳入了患有MRSA BSI的成年患者，这些患者接受了万古霉素、达托霉素或头孢洛林治疗。对先前开发的用于金黄色葡萄球菌BSI的DOOR进行调整，并应用于该队列，以比较万古霉素治疗组和达托霉素/头孢洛林治疗组的患者。DOOR有五个相互排斥的等级：（1）存活且无治疗失败、感染并发症或4级不良事件（AE）；（2）存活且有治疗失败、感染并发症或4级AE中的任何一项；（3）存活且有治疗失败、感染并发症或4级AE中的两项；（4）存活且有治疗失败、感染并发症或4级AE全部三项；或（5）死亡。
共纳入43例接受万古霉素治疗的患者和13例接受达托霉素/头孢洛林治疗的患者。除达托霉素/头孢洛林队列中的血清肌酐中位数较高外（0.76 [IQR 0.57, 1.11] 对比 1.36 [IQR 1.09, 1.91] mg/dL，P = 0.03），基线临床特征相似。使用DOOR方法，达托霉素/头孢洛林队列中的患者有92%的概率获得更好的结局。接受达托霉素/头孢洛林治疗的患者出现MRSA BSI持续存在（0%对比13.9%）、MRSA BSI复发（7.8%对比25.6%）、4级AE（23.1%对比46.5%）和院内死亡率（0%对比9.3%）的情况较少。
尽管受样本量限制，但本研究证明了DOOR产生有价值的、以患者为中心的结果的潜力。鼓励临床医生熟悉DOOR方法的正确使用和解读，因为它将在临床试验中成为越来越常见的终点。
