Kondo Yutaka, Klompas Michael, McKenna Caroline S, Pak Theodore R, Shappell Claire N, DelloStritto Laura, Rhee Chanu
Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA.
Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Bunkyo-Ku, Tokyo, Japan.
Clin Infect Dis. 2025 Apr 30;80(4):761-769. doi: 10.1093/cid/ciae599.
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.
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.
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.
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.
及时开始使用抗生素对脓毒症的治疗至关重要，但对于同时开具了β-内酰胺类药物和万古霉素的患者，先给予β-内酰胺类药物与先给予万古霉素的影响的数据有限。
我们回顾性分析了2015年至2022年期间入住美国5家医院的所有成年疑似脓毒症患者（采集了血培养样本、使用了抗生素并出现器官功能障碍），这些患者在到达后24小时内接受了万古霉素和广谱β-内酰胺类药物治疗。我们使用逆概率加权法（IPW）来调整潜在混杂因素，估计先使用β-内酰胺类药物与先使用万古霉素的策略与院内死亡率之间的关联。
在25391例疑似脓毒症患者中，21449例（84.4%）先接受了β-内酰胺类药物治疗，3942例（15.6%）先接受了万古霉素治疗。与先使用β-内酰胺类药物的组相比，先使用万古霉素的患者病情往往较轻，皮肤/肌肉骨骼感染更多（20.0%对7.8%），并且相对于急诊科到达时间，β-内酰胺类药物的给药时间中位数晚3.5小时。在IPW分析中，先使用β-内酰胺类药物的策略与较低的死亡率相关（调整后的优势比[aOR]：0.89；95%置信区间：0.80-0.99）。在使用倾向评分匹配而非IPW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阳性的患者亚组和接受抗假单胞菌β-内酰胺类药物治疗的患者中，点估计值在方向上相似但无统计学意义（aOR：0.94；95%置信区间：0.82-1.07）。
在同时开具了万古霉素和β-内酰胺类药物治疗的疑似脓毒症患者中，先给予β-内酰胺类药物与院内死亡率适度降低相关。这些发现支持在大多数脓毒症患者中优先使用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，需要在随机试验中得到证实。
