Am J Epidemiol. 2021 Nov 2;190(11):2395-2404. doi: 10.1093/aje/kwab158.
Delays in treating bacteremias with antibiotics to which the causative organism is susceptible are expected to adversely affect patient outcomes. Quantifying the impact of such delays to concordant treatment is important for decision-making about interventions to reduce the delays and for quantifying the burden of disease due to antimicrobial resistance. There are, however, potentially important biases to be addressed, including immortal time bias. We aimed to estimate the impact of delays in appropriate antibiotic treatment of patients with Acinetobacter species hospital-acquired bacteremia in Thailand on 30-day mortality by emulating a target trial using retrospective cohort data from Sunpasitthiprasong Hospital in 2003-2015. For each day, we defined treatment as concordant if the isolated organism was susceptible to at least 1 antibiotic given. Among 1,203 patients with Acinetobacter species hospital-acquired bacteremia, 682 had 1 or more days of delays to concordant treatment. Surprisingly, crude 30-day mortality was lower in patients with delays of ≥3 days compared with those who had 1-2 days of delays. Accounting for confounders and immortal time bias resolved this paradox. Emulating a target trial, we found that these delays were associated with an absolute increase in expected 30-day mortality of 6.6% (95% confidence interval: 0.2, 13.0), from 33.8% to 40.4%.
预计治疗对病原体敏感的菌血症时抗生素的延迟会对患者的预后产生不利影响。量化这种与一致治疗相关的延迟的影响对于减少延迟的干预措施的决策以及量化由于抗生素耐药而导致的疾病负担非常重要。然而，存在一些需要解决的潜在重要偏差，包括不朽时间偏差。我们旨在通过使用 2003 年至 2015 年 Sunpasitthiprasong 医院的回顾性队列数据模拟目标试验，估计泰国获得性医院感染不动杆菌菌血症患者适当抗生素治疗延迟对 30 天死亡率的影响。对于每一天，如果分离的病原体对至少一种给予的抗生素敏感，我们将治疗定义为一致。在 1203 例获得性医院感染不动杆菌菌血症患者中，682 例患者有 1 天或更长时间的延迟至一致治疗。令人惊讶的是，与延迟 1-2 天的患者相比，延迟≥3 天的患者的粗 30 天死亡率较低。考虑到混杂因素和不朽时间偏差，解决了这一悖论。通过模拟目标试验，我们发现这些延迟与预期 30 天死亡率绝对增加 6.6%（95%置信区间：0.2，13.0）相关，从 33.8%增加到 40.4%。
