多粘菌素相关性肾毒性的临床表型和碳青霉烯类耐药鲍曼不动杆菌感染中性粒细胞与血小板比率的表型特异性预后效用
Clinical phenotyping of polymyxin-associated nephrotoxicity and phenotype-specific prognostic utility of neutrophil-to-platelet ratio in carbapenem-resistant Acinetobacter baumannii infections.
摘要(中文译文)
背景：耐碳青霉烯类鲍曼不动杆菌（CRAB）感染在治疗上仍具有挑战性，尽管存在显著的肾毒性，往往仍须使用最后防线的多黏菌素治疗。传统的多黏菌素相关急性肾损伤（AKI）风险评估常常忽视患者的异质性。我们试图描绘多黏菌素相关AKI的临床表型，并确定中性粒细胞与血小板比值（NPR）对死亡率的预后价值是否因表型而异。方法：我们开展了一项回顾性队列研究（2020—2025年），纳入547例接受多黏菌素治疗的CRAB感染患者。采用潜在类别分析（LCA），基于基线危险因素和肾脏结局识别临床表型。采用纳入限制性立方样条（RCS）的多变量logistic回归，随后进行分段回归，评估NPR与28天死亡率之间的非线性关联，并检验表型对效应的修饰作用。结果：LCA揭示了三种不同的表型：严重肾衰竭（类别1，15.2%）、低危/稳定（类别2，62.0%）和高合并症/非RRT严重损伤（类别3，22.8%）。这些表型之间的基线特征和28天死亡率存在显著差异（9.6% vs. 4.4% vs. 8.6%；p = 0.033）。NPR的预后价值仅在类别2中显著，在该类别中发现了0.0167的临界阈值效应（断点检验p < 0.001）。低于该阈值时，死亡风险急剧上升——这种非线性关系在高严重度表型（类别1和3）中被掩盖。结论：接受多黏菌素治疗的CRAB感染患者表现出三种不同的肾毒性表型。NPR的预后效用具有表型特异性，临界阈值0.0167仅在低危/稳定亚组中识别出相对免疫不足。因此，临床表型分型是该人群中准确解读生物标志物和进行个体化风险分层的先决条件。临床试验编号：不适用。
Abstract
BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) infections remain therapeutically challenging, often necessitating last-line polymyxin therapy despite substantial nephrotoxicity. Conventional risk assessments for polymyxin-associated acute kidney injury (AKI) frequently overlook patient heterogeneity. We sought to delineate clinical phenotypes of polymyxin-associated AKI and determine whether the prognostic value of the neutrophil-to-platelet ratio (NPR) for mortality varies by phenotype. METHODS: We conducted a retrospective cohort study (2020–2025) of 547 patients with CRAB infections treated with polymyxins. Latent class analysis (LCA) identified clinical phenotypes using baseline risk factors and renal outcomes. Multivariable logistic regression incorporating restricted cubic splines (RCS), followed by piecewise regression, evaluated non-linear associations between NPR and 28-day mortality and tested effect modification by phenotype. RESULTS: LCA revealed three distinct phenotypes: Severe Renal Failure (Class 1, 15.2%), Low-risk/Stable (Class 2, 62.0%), and High-Comorbidity/Non-RRT Severe Injury (Class 3, 22.8%). Baseline characteristics and 28-day mortality varied significantly across these phenotypes (9.6% vs. 4.4% vs. 8.6%; p = 0.033). The prognostic value of NPR was exclusively significant in Class 2, where a critical threshold effect was identified at 0.0167 (breakpoint test p < 0.001). Below this threshold, mortality risk rose sharply—a non-linear relationship that was obscured in high-severity phenotypes (Class 1 and 3). CONCLUSION: Patients with CRAB infections receiving polymyxins exhibit three distinct nephrotoxicity phenotypes. The prognostic utility of NPR is phenotype-specific, with a critical threshold at 0.0167 identifying relative immune insufficiency exclusively within the Low-risk/Stable subgroup. Clinical phenotyping is therefore a prerequisite for accurate biomarker interpretation and personalized risk stratification in this population. CLINICAL TRIAL NUMBER: Not applicable.
如何引用
AMA
Haixing Zhu, Dake Shi, Guangwei Li, Lijuan Wu, Xiaoqian Ma, Jiebai Zhou, et al. Clinical phenotyping of polymyxin-associated nephrotoxicity and phenotype-specific prognostic utility of neutrophil-to-platelet ratio in carbapenem-resistant Acinetobacter baumannii infections.. BMC infectious diseases. 2026; doi:10.1186/s12879-026-12964-w.
APA
Haixing Zhu, Dake Shi, Guangwei Li, Lijuan Wu, Xiaoqian Ma, Jiebai Zhou, et al (2026). Clinical phenotyping of polymyxin-associated nephrotoxicity and phenotype-specific prognostic utility of neutrophil-to-platelet ratio in carbapenem-resistant Acinetobacter baumannii infections.. BMC infectious diseases. https://doi.org/10.1186/s12879-026-12964-w
GB/T 7714
Haixing Zhu, Dake Shi, Guangwei Li, Lijuan Wu, Xiaoqian Ma, Jiebai Zhou, et al. Clinical phenotyping of polymyxin-associated nephrotoxicity and phenotype-specific prognostic utility of neutrophil-to-platelet ratio in carbapenem-resistant Acinetobacter baumannii infections.[J]. BMC infectious diseases, 2026 doi:10.1186/s12879-026-12964-w.
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