Microbiological spectrum, clinical outcomes, and risk factors for bloodstream infections during immune checkpoint inhibitor therapy: a nested case-control study

Immune checkpoint inhibitors (ICIs) modulate host immunity and may increase infection risk. The pathogen profile, outcomes, and predictors of bloodstream infections (BSIs) in ICI recipients are not well defined; we aimed to characterise these features and identify independent risk factors.
We performed a retrospective nested case–control study within a cohort of 2,584 adult cancer patients who received ICIs at a tertiary centre from January 2018 to December 2023. We identified 185 BSI cases occurring during or within 90 days after the last ICI dose and matched each case 1:2 to infection-free controls by cancer type, ICI agent, and time at risk. Demographics, comorbidities, cancer and treatment details, laboratory values, concomitant medications, and outcomes were extracted and analysed using conditional logistic regression.
Cases (median age 62 years; 65.4% male) had predominance of gram-positive organisms (54.1%), led by Staphylococcus aureus (18.4%) and Enterococcus spp. (12.4%); gram-negatives comprised 37.8% with Escherichia coli being the most frequent (15.1%), and opportunistic pathogens (Listeria, Candida) made up 8.1%. Multivariable analysis identified prior corticosteroid use ≥14 days (prednisone equivalent ≥10 mg/day for ≥14 days; adjusted odds ratio [aOR], 4.12; 95% CI, 2.58–6.59; p < 0.001), proton pump inhibitor use (aOR 2.05; 95% CI 1.31–3.22), and baseline absolute lymphocyte count <1.0 × 10^9/L (aOR 2.33; 95% CI 1.48–3.68) as independent predictors. All-cause 30-day mortality among cases was 24.9%.
BSIs in ICI-treated patients involve a broad pathogen spectrum, including opportunists and are associated with substantial mortality; corticosteroid exposure, PPI use, and lymphopenia identify high-risk patients who may benefit from targeted surveillance and preventive strategies.

免疫检查点抑制剂（Immune checkpoint inhibitors，ICIs）可调节宿主免疫功能，并可能增加感染风险。免疫检查点抑制剂使用者的血流感染（Bloodstream infections，BSIs）病原体谱、临床转归及预测因素尚未明确；本研究旨在阐明上述特征并明确独立危险因素。

本研究于2018年1月至2023年12月期间，在某三级医疗中心接受免疫检查点抑制剂治疗的2584例成年癌症患者队列中，开展了一项回顾性巢式病例对照研究。共纳入末次免疫检查点抑制剂给药期间或给药后90天内发生血流感染的185例病例，并按照癌症类型、免疫检查点抑制剂种类及暴露风险时间以1:2比例匹配无感染对照。提取研究对象的人口学特征、合并症、癌症及治疗相关细节、实验室指标、合并用药情况与临床转归，采用条件logistic回归进行分析。

病例组患者中位年龄为62岁，男性占比65.4%；血流感染病原体以革兰阳性菌为主（54.1%），前两位依次为金黄色葡萄球菌（18.4%）与肠球菌属（12.4%）；革兰阴性菌占比37.8%，以大肠埃希菌最为常见（15.1%）；机会致病菌（李斯特菌属、念珠菌属）占比8.1%。多变量分析显示，既往糖皮质激素使用≥14天（泼尼松等效剂量≥10mg/天，持续≥14天；校正比值比[adjusted odds ratio，aOR]=4.12，95%置信区间[CI]：2.58~6.59；P<0.001）、质子泵抑制剂（proton pump inhibitor，PPI）使用（aOR=2.05，95%CI：1.31~3.22）以及基线绝对淋巴细胞计数<1.0×10^9/L（aOR=2.33，95%CI：1.48~3.68）为独立预测因素。病例组患者的全因30天死亡率为24.9%。

接受免疫检查点抑制剂治疗患者的血流感染病原体谱广泛，涵盖机会致病菌，且与较高的临床死亡率相关；糖皮质激素暴露、质子泵抑制剂使用及淋巴细胞减少可识别出高危患者，此类患者或可从针对性监测与预防策略中获益。