PDF(Pubmed)
Abstract：
UNASSIGNED: Current evidence is conflicting for associations of extended-infusion β-lactam (EI-BL) therapy with clinical outcomes.
UNASSIGNED: To investigate the association of EI-BL therapy with survival, adverse events, and emergence of antibiotic resistance in adults with gram-negative bloodstream infections (GN-BSI).
UNASSIGNED: This cohort study of consecutive adults with GN-BSI admitted to 24 United States hospitals between January 1, 2019, and December 31, 2019, receiving EI-BL were compared with adults with GN-BSI receiving the same agents as intermittent infusion β-lactam (II-BL; ≤1-hour infusions). Statistical analysis was performed from January to October 2023.
UNASSIGNED: EI-BL (ie, ≥3-hour infusion).
UNASSIGNED: EI-BL and II-BL groups underwent 1:3 nearest-neighbor propensity score matching (PSM) without replacement. Multivariable regression was applied to the PSM cohort to investigate outcomes, all censored at day 90. The primary outcome was mortality; secondary outcomes included antibiotic adverse events and emergence of resistance (≥4-fold increase in the minimum inhibitory concentration of the β-lactam used to treat the index GN-BSI).
UNASSIGNED: Among the 4861 patients included, 2547 (52.4%) were male; and the median (IQR) age was 67 (55-77) years. There were 352 patients in the EI-BL 1:3 PSM group, and 1056 patients in the II-BL 1:3 PSM group. Among 1408 PSM patients, 373 (26.5%) died by day 90. The odds of mortality were lower in the EI-BL group (adjusted odds ratio [aOR], 0.71 [95% CI, 0.52-0.97]). In a stratified analysis, a survival benefit was only identified in patients with severe illness or elevated minimum inhibitory concentrations (ie, in the intermediate range for the antibiotic administered). There were increased odds of catheter complications (aOR, 3.14 [95% CI, 1.66-5.96]) and antibiotic discontinuation because of adverse events (eg, acute kidney injury, cytopenias, seizures) in the EI-BL group (aOR, 3.66 [95% CI, 1.68-7.95]). Emergence of resistance was similar in the EI-BL and II-BL groups at 2.9% vs 7.2%, respectively (P = .35).
UNASSIGNED: In this cohort study of patients with GN-BSI, EI-BL therapy was associated with reduced mortality for patients with severe illness or those infected with nonsusceptible organisms; potential advantages in other groups remain unclear and need to be balanced with potential adverse events. The subsequent emergence of resistance warrants investigation in a larger cohort.
UNASSIGNED: To investigate the association of EI-BL therapy with survival, adverse events, and emergence of antibiotic resistance in adults with gram-negative bloodstream infections (GN-BSI).
UNASSIGNED: This cohort study of consecutive adults with GN-BSI admitted to 24 United States hospitals between January 1, 2019, and December 31, 2019, receiving EI-BL were compared with adults with GN-BSI receiving the same agents as intermittent infusion β-lactam (II-BL; ≤1-hour infusions). Statistical analysis was performed from January to October 2023.
UNASSIGNED: EI-BL (ie, ≥3-hour infusion).
UNASSIGNED: EI-BL and II-BL groups underwent 1:3 nearest-neighbor propensity score matching (PSM) without replacement. Multivariable regression was applied to the PSM cohort to investigate outcomes, all censored at day 90. The primary outcome was mortality; secondary outcomes included antibiotic adverse events and emergence of resistance (≥4-fold increase in the minimum inhibitory concentration of the β-lactam used to treat the index GN-BSI).
UNASSIGNED: Among the 4861 patients included, 2547 (52.4%) were male; and the median (IQR) age was 67 (55-77) years. There were 352 patients in the EI-BL 1:3 PSM group, and 1056 patients in the II-BL 1:3 PSM group. Among 1408 PSM patients, 373 (26.5%) died by day 90. The odds of mortality were lower in the EI-BL group (adjusted odds ratio [aOR], 0.71 [95% CI, 0.52-0.97]). In a stratified analysis, a survival benefit was only identified in patients with severe illness or elevated minimum inhibitory concentrations (ie, in the intermediate range for the antibiotic administered). There were increased odds of catheter complications (aOR, 3.14 [95% CI, 1.66-5.96]) and antibiotic discontinuation because of adverse events (eg, acute kidney injury, cytopenias, seizures) in the EI-BL group (aOR, 3.66 [95% CI, 1.68-7.95]). Emergence of resistance was similar in the EI-BL and II-BL groups at 2.9% vs 7.2%, respectively (P = .35).
UNASSIGNED: In this cohort study of patients with GN-BSI, EI-BL therapy was associated with reduced mortality for patients with severe illness or those infected with nonsusceptible organisms; potential advantages in other groups remain unclear and need to be balanced with potential adverse events. The subsequent emergence of resistance warrants investigation in a larger cohort.
摘要：
■目前的证据表明延长输注β-内酰胺（EI-BL）治疗与临床结果的关系是相互矛盾的。
■为了研究EI-BL治疗与生存率的关系，不良事件,以及革兰阴性血流感染（GN-BSI）成人中抗生素耐药性的出现。
■这项队列研究对2019年1月1日至2019年12月31日期间在美国24家医院接受EI-BL治疗的连续GN-BSI成年人与接受与间歇性输注β-内酰胺（II-BL；≤1小时输注）相同药物的GN-BSI成年人进行了比较。统计分析于2023年1月至10月进行。
■EI-BL（即，≥3小时输注)。
■EI-BL组和II-BL组进行了1：3最近邻倾向评分匹配（PSM）而无需更换。将多变量回归应用于PSM队列以调查结果，都在第90天审查。主要结果是死亡率；次要结果包括抗生素不良事件和耐药性的出现（用于治疗GN-BSI指数的β-内酰胺的最小抑制浓度增加≥4倍）。
■在4861名患者中，2547（52.4％）为男性；中位（IQR）年龄为67（55-77）岁。EI-BL1:3PSM组中有352例患者，II-BL1:3PSM组1056例患者。在1408名PSM患者中，到第90天，373人（26.5%）死亡。EI-BL组的死亡率较低(调整后的优势比[aOR]，0.71[95%CI，0.52-0.97]）。在分层分析中，仅在患有严重疾病或最低抑制浓度升高的患者中确定了生存益处（即，在施用的抗生素的中间范围内)。导管并发症的可能性增加(aOR，3.14[95%CI，1.66-5.96]）和因不良事件而停用抗生素（例如，急性肾损伤，血细胞减少,癫痫发作)在EI-BL组(aOR，3.66[95%CI，1.68-7.95]）。在EI-BL和II-BL组中，耐药性的出现相似，分别为2.9％和7.2％，分别(P=.35)。
■在这项GN-BSI患者的队列研究中，对于患有严重疾病或感染非易感生物的患者，EI-BL治疗与死亡率降低相关；其他组的潜在优势尚不清楚，需要与潜在的不良事件进行平衡。抵抗的随后出现需要在更大的队列中进行调查。
■为了研究EI-BL治疗与生存率的关系，不良事件,以及革兰阴性血流感染（GN-BSI）成人中抗生素耐药性的出现。
■这项队列研究对2019年1月1日至2019年12月31日期间在美国24家医院接受EI-BL治疗的连续GN-BSI成年人与接受与间歇性输注β-内酰胺（II-BL；≤1小时输注）相同药物的GN-BSI成年人进行了比较。统计分析于2023年1月至10月进行。
■EI-BL（即，≥3小时输注)。
■EI-BL组和II-BL组进行了1：3最近邻倾向评分匹配（PSM）而无需更换。将多变量回归应用于PSM队列以调查结果，都在第90天审查。主要结果是死亡率；次要结果包括抗生素不良事件和耐药性的出现（用于治疗GN-BSI指数的β-内酰胺的最小抑制浓度增加≥4倍）。
■在4861名患者中，2547（52.4％）为男性；中位（IQR）年龄为67（55-77）岁。EI-BL1:3PSM组中有352例患者，II-BL1:3PSM组1056例患者。在1408名PSM患者中，到第90天，373人（26.5%）死亡。EI-BL组的死亡率较低(调整后的优势比[aOR]，0.71[95%CI，0.52-0.97]）。在分层分析中，仅在患有严重疾病或最低抑制浓度升高的患者中确定了生存益处（即，在施用的抗生素的中间范围内)。导管并发症的可能性增加(aOR，3.14[95%CI，1.66-5.96]）和因不良事件而停用抗生素（例如，急性肾损伤，血细胞减少,癫痫发作)在EI-BL组(aOR，3.66[95%CI，1.68-7.95]）。在EI-BL和II-BL组中，耐药性的出现相似，分别为2.9％和7.2％，分别(P=.35)。
■在这项GN-BSI患者的队列研究中，对于患有严重疾病或感染非易感生物的患者，EI-BL治疗与死亡率降低相关；其他组的潜在优势尚不清楚，需要与潜在的不良事件进行平衡。抵抗的随后出现需要在更大的队列中进行调查。
