Reply to Kalil et al., "Is Daptomycin plus Ceftaroline Associated with Better Clinical Outcomes than Standard of Care Monotherapy for Staphylococcus aureus Bacteremia?".
Reply to Kalil et al., "Is Daptomycin plus Ceftaroline Associated with Better Clinical Outcomes than Standard of Care Monotherapy for Staphylococcus aureus Bacteremia?".
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回复 Kalil 等人，“达托霉素加头孢洛林与金黄色葡萄球菌菌血症的标准护理单一疗法相比是否具有更好的临床结果？”。
DOI：
10.1128/aac.01347-19
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发表时间：
2019
影响因子：
4.9
通讯作者：
Nizet,Victor
中科院分区：
文献类型：
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作者：
Sakoulas,George;Geriak,Matthew;Haddad,Fadi;Rose,Warren;LaPlante,Kerry;Zervos,Marcus;Kullar,Ravina;Nizet,Victor
我们感谢Kalil等人对Geriak等人研究结果的评论。（一）.我们意识到所提到的方法上的局限性，正如我们的文件中所讨论的那样。因此，我们承认，我们的研究福尔斯没有达到被认为是“改变实践”的临床试验的强烈期望。鉴于这些限制对实践的潜在影响，我们赞赏对这些限制的批判性评论。Kalil等人的信暗示，标准治疗单药治疗患者组的死亡率高于联合治疗患者组，因为合并症对他们不利。他们强调了单药治疗患者的“缺点”，而没有提到联合治疗组的“缺点”，所有这些都是数值差异，而不是统计学差异。虽然较高的降钙素原和C-反应蛋白浓度表明单药治疗组“炎症状态更严重”，但重要的是要注意联合治疗组的白色血细胞计数、白细胞介素-10浓度和心内膜炎患者数量更高。在以前的研究中，只有年龄、血管内来源和肾功能不全是金黄色葡萄球菌菌血症死亡率的一致预测因素（2）。在Geriak研究中，标准护理患者人群的住院/30天死亡率为26%，完全在耐甲氧西林链球菌死亡率的预期范围内。金黄色葡萄球菌（MRSA）菌血症（2）。本研究的差异是联合治疗组的死亡率为0%，尽管Charlson合并症和Pitt菌血症评分与单药治疗组相似。Kalil等人指出，本试验中的随机化是“有缺陷的”。我们指出，单药治疗组（23例患者）比联合治疗组（17例患者）有更多的患者，这是一个偶然事件。每组患者的百分比（57.5%/42.5%）与Juul等人最近报告的粪便微生物群移植的小型随机试验（55%/45%）中的患者分配相似。（三）、由于偶然性，这可能发生在早期入组期间，但随着时间的推移，随着继续随机化，这通常会发生，由于提前终止，这在我们的研究中不会发生。Kalil等人认为，由于患者数量较少，任何一种方式的患者都会使结果偏离统计学显著性，这是正确的，但由于研究不是以设盲方式进行的，因此继续进行本研究会带来伦理困境，为了统计学的完美性，不允许继续进行。一个数据安全监测委员会，虽然理想，没有资助，和一个非盲研究，
We appreciate the comments by Kalil et al. regarding the results of the study by Geriak et al.(1). We are aware of the methodological limitations mentioned, as they are discussed in our paper. As a result, we acknowledge that our study falls short of the robust expectations of what would be considered a “practice-changing” clinical trial. We applaud a critical commentary on these limitations given the potential implications on practice.The letter by Kalil et al. implies that the standard of care monotherapy patient group had a higher mortality than the combination therapy patients because the deck was stacked against them with respect to comorbidities. They highlight the “disadvantages” of the monotherapy patients without mentioning the “disadvantages” of the combination group, all of which are numerical rather than statistical differences. While the higher procalcitonin and C-reactive protein concentrations suggest “a more inflammatory state” in the monotherapy group, it is important to note that white blood cell count, interleukin-10 concentrations, and number of endocarditis patients were higher in the combination patient group. In previous studies, only age, endovascular source, and renal insufficiency are consistent predictors of mortality in Staphylococcus aureus bacteremia (2). The 26% in-hospital/30-day mortality seen with standard of care patient population in the Geriak study is well within expectations of mortality for methicillinresistant S. aureus (MRSA) bacteremia (2). The difference in this study was the 0% mortality in the combination group, despite having Charlson comorbidity and Pitt bacteremia scores that were similar to those of the monotherapy group. Kalil et al. state that the randomization in this trial was “flawed.” We point out that a matter of chance brought more patients in the monotherapy arm (23 patients) than the combination arm (17 patients). The percentage of patients in each group (57.5%/42.5%) was similar to the allocation of patients in a recent small randomized trial of fecal microbiota transplant (55%/45%) reported by Juul et al.(3). This can occur during early enrollment due to chance but will often even out over time with continued randomization, which could not occur in our study due to early termination. Kalil et al. are correct that one patient either way would sway results away from statistical significance due to the small number of patients, but as the study was not carried out in a blinded manner, continuation of this study posed an ethical dilemma that could not allow continuation for the sake of statistical perfection. A data safety monitoring board, while ideal, was not funded for, and an nonblinded study such as