Background Timely antibiotic initiation is critical to sepsis management, but there are limited data on the impact of giving β-lactams first versus vancomycin first among patients prescribed both agents. Methods We retrospectively analyzed all adults admitted to 5 US hospitals from 2015–2022 with suspected sepsis (blood culture collected, antibiotics administered, and organ dysfunction) treated with vancomycin and a broad-spectrum β-lactam within 24 hours of arrival. We estimated associations between β-lactam- versus vancomycin-first strategies and in-hospital mortality using inverse probability weighting (IPW) to adjust for potential confounders. Results Among 25 391 patients with suspected sepsis, 21 449 (84.4%) received β-lactams first and 3942 (15.6%) received vancomycin first. Compared with the β-lactam-first group, patients administered vancomycin first tended to be less severely ill, had more skin/musculoskeletal infections (20.0% vs 7.8%), and received β-lactams a median of 3.5 hours later relative to emergency department arrival. On IPW analysis, the β-lactam-first strategy was associated with lower mortality (adjusted odds ratio [aOR]: .89; 95% CI: .80–.99). Point estimates were directionally similar but nonsignificant in a sensitivity analysis using propensity score matching rather than IPW (aOR: .94; 95% CI: .82–1.07) and in subgroups of patients with positive blood cultures, methicillin-resistant Staphylococcus aureus cultures, and those administered antipseudomonal β-lactams. Conclusions Among patients with suspected sepsis prescribed vancomycin and β-lactam therapy, β-lactam administration before vancomycin was associated with a modest reduction in in-hospital mortality. These findings support prioritizing β-lactam therapy in most patients with sepsis but merit confirmation in randomized trials given the risk of residual confounding in observational analyses.

中文翻译：

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β-内酰胺类药物和万古霉素给药顺序与疑似脓毒症患者死亡率的相关性


背景 及时开始使用抗生素对于脓毒症管理至关重要，但在开具两种药物的患者中，关于先给予 β-内酰胺类药物与先给予万古霉素影响的数据有限。方法 我们回顾性分析了 2015-2022 年美国 5 家医院收治的所有疑似脓毒症 （血培养采集、抗生素给药和器官功能障碍） 成人，在抵达后 24 小时内接受万古霉素和广谱 β-内酰胺类药物治疗。我们使用逆概率加权 （IPW） 估计了 β-内酰胺与万古霉素优先策略与院内死亡率之间的关联，以调整潜在的混杂因素。结果 25 391 例疑似脓毒症患者中，21 449 例 （84.4%） 首先接受β-内酰胺类药物，3942 例 （15.6%） 首先接受万古霉素治疗。与 β-内酰胺类药物优先组相比，首次接受万古霉素治疗的患者病情往往较轻，皮肤/肌肉骨骼感染更多 （20.0% 对 7.8%），并且接受 β-内酰胺类药物的中位时间晚 3.5 小时相对于急诊科到达。在 IPW 分析中，β-内酰胺类药物优先策略与较低的死亡率相关 （校正比值比 [aOR]： .89;95% CI： .80–.99）。在使用倾向评分匹配而不是 IPW （aOR： .94;95% CI： .82–1.07） 的敏感性分析中，以及在血培养阳性、耐甲氧西林金黄色葡萄球菌培养和接受抗假单胞菌 β-内酰胺类药物的患者亚组中，点估计值在方向上相似但不显著。结论 在接受万古霉素和 β-内酰胺治疗的疑似脓毒症患者中，万古霉素前给予 β-内酰胺类药物与院内死亡率的适度降低相关。 这些发现支持大多数脓毒症患者优先考虑 β-内酰胺类药物治疗，但鉴于观察性分析中存在残留混杂的风险，值得在随机试验中得到证实。