McMahon Stephanie, Franklin Samantha, Galloway-Peña Jessica
Laboratory of Jessica Galloway-Peña, Texas A&M University, Department of Veterinary Pathobiology, Interdisciplinary Graduate Program in Genetics and Genomics, College Station, TX, United States.
Front Cell Infect Microbiol. 2025 Aug 21;15:1629422. doi: 10.3389/fcimb.2025.1629422. eCollection 2025.
Acute myeloid leukemia (AML) patients are highly susceptible to infection. Moreover, prophylactic and empirical antibiotic treatment during chemotherapy disrupts the gut microbiome, raising the risk for antibiotic-resistant (AR) opportunistic pathogens. There is limited data on risk factors for AR infections or colonization events in treated cancer patients, and no predictive models exist. This study aims to combine metagenomic and antibiotic administration data to develop a model predicting AR event outcomes.
Baseline stool microbiome, antibiotic administration, resistome, and clinical metadata from 95 patients were utilized to build a Random Forest model to predict AR infection and colonization events by serious AR threats. Additionally, sparse canonical correlation analysis assessed correlations between microbiome and resistome data, while Spearman correlation networks identified direct associations with AR event outcomes and secondary variables.
AR-events were identified in 14 of the 95 included patients, with 8 developing AR infections and 9 identified as AR colonized. A Random Forest model predicted AR event outcomes (AUC = 0.73), identifying bacterial taxa and antibiotic resistance gene (ARG) classes as key variables of importance. , and were identified as key taxa associated with reduced risk of AR events, suggesting the potential roles of commensals in maintaining gut microbial resilience during chemotherapy. ARG classes, particularly those conferring resistance to lincosamides, macrolides, and streptogramins, were negatively associated with AR events.
These results underscore the value of integrating microbiome and resistome features to reveal potential protective mechanisms and improve risk prediction for AR outcomes in vulnerable patients.
急性髓系白血病(AML)患者极易感染。此外,化疗期间的预防性和经验性抗生素治疗会破坏肠道微生物群,增加对抗生素耐药(AR)的机会性病原体的风险。关于接受治疗的癌症患者发生AR感染或定植事件的危险因素的数据有限,且尚无预测模型。本研究旨在结合宏基因组学和抗生素给药数据,建立一个预测AR事件结局的模型。
利用95例患者的基线粪便微生物群、抗生素给药、耐药基因组和临床元数据,构建随机森林模型,以预测严重AR威胁导致的AR感染和定植事件。此外,稀疏典型相关分析评估了微生物群与耐药基因组数据之间的相关性,而斯皮尔曼相关网络确定了与AR事件结局和次要变量的直接关联。
在纳入的95例患者中,有14例发生了AR事件,其中8例发生了AR感染,9例被确定为AR定植。随机森林模型预测了AR事件结局(曲线下面积 = 0.73),确定细菌分类群和抗生素耐药基因(ARG)类别为重要的关键变量。 和 被确定为与AR事件风险降低相关的关键分类群,表明共生菌在化疗期间维持肠道微生物弹性方面的潜在作用。ARG类别,特别是那些赋予对林可酰胺类、大环内酯类和链阳菌素类耐药性的类别,与AR事件呈负相关。
这些结果强调了整合微生物群和耐药基因组特征以揭示潜在保护机制并改善对脆弱患者AR结局风险预测的价值。