Cefazolin for Methicillin-Susceptible Staphylococcus aureus Bacteremia.

Whether cefazolin or an antistaphylococcal penicillin should be preferred for the treatment of methicillin-susceptible S. aureus bacteremia is unclear.

对于甲氧西林敏感的金黄色葡萄球菌菌血症，是首选使用头孢唑林还是抗葡萄球菌青霉素进行治疗尚不明确。

Methods

In an ongoing international Bayesian adaptive platform trial, we conducted an open-label, randomized comparison of cefazolin with an antistaphylococcal penicillin (flucloxacillin or cloxacillin) in adult patients with penicillin-resistant, methicillin-susceptible S. aureus bacteremia.

在一项正在进行的国际贝叶斯自适应平台试验中，我们对成人患者进行了头孢唑林与抗葡萄球菌青霉素（氟氯西林或氯唑西林）的开放标签、随机比较，这些患者患有耐青霉素、甲氧西林敏感的金黄色葡萄球菌菌血症。

The primary outcome, which was evaluated with a hierarchical Bayesian logistic-regression model, was death from any cause within 90 days after enrollment in the platform.

主要结果是通过分层贝叶斯逻辑回归模型评估的，即在加入平台后90天内因任何原因导致的死亡。

We assessed the posterior probability of the noninferiority of cefazolin to flucloxacillin or cloxacillin (with the criterion for noninferiority prespecified as an adjusted odds ratio of <1.2, which approximates an absolute difference in mortality of <2.5 percentage points if mortality in the antistaphylococcal-penicillin group is 15%), as well as the posterior probability of superiority (with the criterion of an adjusted odds ratio of <1.0).

我们评估了头孢唑林与氟氯西林或氯唑西林非劣效性的后验概率（非劣效性标准预设为调整后的比值比<1.2，这大致相当于如果抗葡萄球菌青霉素组的死亡率为15%，则死亡率的绝对差异<2.5个百分点），以及优势性的后验概率（优势性标准为调整后的比值比<1.0）。

Secondary safety outcomes included the development of acute kidney injury within 14 days.

次要安全性结果包括14天内发生急性肾损伤的情况。

Results

This domain of the ongoing trial was conducted between February 17, 2022, and August 7, 2024, by which time the criterion for noninferiority had been met.

该试验的这一部分是在2022年2月17日至2024年8月7日之间进行的，在此期间达到了非劣效性的标准。

Mortality at 90 days among adults who could be evaluated was 15.0% (97 deaths among 645 patients) in the cefazolin group and 17.0% (109 deaths among 642 patients) in the antistaphylococcal-penicillin group (adjusted odds ratio, 0.81; 95% credible interval, 0.59 to 1.12; probability of noninferiority, 99.2%; probability of superiority, 89.8%).

在可评估的成人患者中，头孢唑林组90天的死亡率为15.0%（645名患者中有97人死亡），抗葡萄球菌青霉素组为17.0%（642名患者中有109人死亡）（调整后的优势比为0.81；95%可信区间为0.59至1.12；非劣效性的概率为99.2%；优越性的概率为89.8%）。

Acute kidney injury occurred in 92 of 660 patients (13.9%) in the cefazolin group, as compared with 127 of 648 (19.6%) in the antistaphylococcal-penicillin group (adjusted odds ratio, 0.67; 95% credible interval, 0.50 to 0.89; probability of superiority, 99.7%).

在接受头孢唑林治疗的660名患者中，有92名（13.9%）发生了急性肾损伤，而在648名接受抗葡萄球菌青霉素治疗的患者中，有127名（19.6%）发生了急性肾损伤（调整后的比值比为0.67；95%可信区间为0.50至0.89；优势概率为99.7%）。

Conclusions

In patients with methicillin-susceptible S. aureus bacteremia, cefazolin was noninferior to flucloxacillin or cloxacillin with respect to 90-day mortality and was associated with a lower incidenceof acute kidney injury.

在甲氧西林敏感金黄色葡萄球菌菌血症患者中，头孢唑林在90天死亡率方面不劣于氟氯西林或氯唑西林，并且与较低的急性肾损伤发生率相关。

(Funded by the National Health and Medical Research Council and others; SNAP ClinicalTrials.gov number, NCT05137119.).

(由国家卫生和医学研究委员会等资助; SNAP ClinicalTrials.gov编号, NCT05137119.)