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癌症患者菌血症中抗菌药物耐药性的流行病学及超额死亡率:一项队列研究,使用2008 - 2018年牛津和奥斯陆地区医院信托常规收集的健康数据

Epidemiology and excess mortality of antimicrobial resistance in bacteraemias among cancer patients: a cohort study using routinely collected health data from regional hospital trusts in Oxford and Oslo, 2008-2018.

作者信息

Danielsen Anders Skyrud, Lim Cherry, Yoon Chang Ho, Gran Jon Michael, Kacelnik Oliver, Eyre David W, Bjørnholt Jørgen Vildershøj

机构信息

Department of Microbiology, Oslo University Hospital, Oslo, Norway

Department of Infection Control and Preparedness, Norwegian Institute of Public Health, Oslo, Norway.

出版信息

BMJ Open. 2025 Jun 13;15(6):e092740. doi: 10.1136/bmjopen-2024-092740.

Abstract

OBJECTIVES

We investigated the epidemiology and impact on mortality of antimicrobial resistance (AMR) in cancer patients with bacteraemia at Oxford University Hospitals (OxUH), UK, and Oslo University Hospital (OsUH), Norway, during 2008-2018.

DESIGN

Historical cohort study.

SETTING

Regional hospital trusts with multiple sites in OxUH and OsUH.

METHODS

Patients with cancer and blood cultures positive for one of six pathogen groups during a hospital stay within 3 years following their first cancer diagnosis were followed for 30 days after their first bacteraemia episode. We determined the number of cases and the proportion of infections with an AMR phenotype. Excess mortality and the population-attributable fraction (PAF) due to AMR were estimated by contrasting observed mortality at the end of follow-up with an estimated counterfactual scenario where AMR was absent from all bacteraemias, using inverse probability weighting.

MAIN OUTCOME MEASURE

30-day all-cause mortality following the first bacteraemia episode.

MAIN EXPOSURE MEASURE

A resistant phenotype of the causative pathogen.

RESULTS

The study included 1929 patients at OxUH and 1640 patients at OsUH. The highest resistance proportions were found for vancomycin resistance in enterococci (85/314, 27.1%) and carbapenem-resistance in (63/260, 24.2%) at OxUH, and third-generation cephalosporin resistance in (62/743, 8.3%) and (14/223, 6.3%) at OsUH. Observed mortality for all infections was 26.4% at OxUH, with an estimated counterfactual mortality without AMR of 24.7%, yielding an excess mortality of 1.7% (95% CI: 0.8 to 2.5%). The PAF was 6.3% (95% CI: 2.9 to 9.6%), meaning an estimated 32 of 509 deaths could be attributed to AMR. Limited events at OsUH precluded a similar estimate.

CONCLUSIONS

Despite estimating modest excess mortality, the mortality attributable to resistance in these two high-income, low-prevalence settings highlights the potential for escalation if global resistance trends continue to worsen.

摘要

目的

我们调查了2008年至2018年期间英国牛津大学医院(OxUH)和挪威奥斯陆大学医院(OsUH)癌症菌血症患者的抗菌药物耐药性(AMR)的流行病学及其对死亡率的影响。

设计

历史性队列研究。

设置

OxUH和OsUH中多个地点的地区医院信托机构。

方法

在首次癌症诊断后的3年内,对住院期间六种病原体组之一血培养呈阳性的癌症患者,在首次菌血症发作后随访30天。我们确定了病例数和具有AMR表型的感染比例。通过使用逆概率加权法,将随访结束时观察到的死亡率与假设所有菌血症均无AMR的估计反事实情况进行对比,估计AMR导致的超额死亡率和人群归因分数(PAF)。

主要结局指标

首次菌血症发作后的30天全因死亡率。

主要暴露指标

致病病原体的耐药表型。

结果

该研究纳入了OxUH的1929例患者和OsUH的1640例患者。在OxUH,肠球菌对万古霉素的耐药比例最高(85/314,27.1%),对碳青霉烯类的耐药比例为(63/260,24.2%);在OsUH,对第三代头孢菌素的耐药比例在(62/743,8.3%)和(14/223,6.3%)。OxUH所有感染的观察到的死亡率为26.4%,估计无AMR时的反事实死亡率为24.7%,超额死亡率为1.7%(95%CI:0.8至2.5%)。PAF为6.3%(95%CI:2.9至9.6%),这意味着509例死亡中估计有32例可归因于AMR。OsUH的事件数量有限,无法进行类似的估计。

结论

尽管估计的超额死亡率不高,但在这两个高收入、低患病率的环境中,耐药导致的死亡率凸显了如果全球耐药趋势继续恶化可能出现的升级情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2311/12164652/3d25b22ee20f/bmjopen-15-6-g001.jpg

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