Olvera Adilene, Carter Hannah, Rajan Anubama, Carlin Lily G, Yu Xiaomin, Zeng Xi-Lei, Shelburne Samuel, Bhatti Micah, Blutt Sarah E, Shroyer Noah F, Jenq Robert, Estes Mary K, Maresso Anthony, Okhuysen Pablo C
Department of Infectious Diseases, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, Houston, Texas, USA.
Clin Infect Dis. 2021 May 18;72(10):e620-e629. doi: 10.1093/cid/ciaa1394.
The role of enteropathogenic Escherichia coli (EPEC) as a cause of diarrhea in cancer and immunocompromised patients is controversial. Quantitation of fecal bacterial loads has been proposed as a method to differentiate colonized from truly infected patients.
We studied 77 adult cancer and immunosuppressed patients with diarrhea and EPEC identified in stools by FilmArray, 25 patients with pathogen-negative diarrhea, and 21 healthy adults without diarrhea. Stools were studied by quantitative polymerase chain reaction (qRT-PCR) for EPEC genes eaeA and lifA/efa-1 and strains characterized for virulence factors and adherence to human intestinal enteroids (HIEs).
Patients with EPEC were more likely to have community-acquired diarrhea (odds ratio, 3.82 [95% confidence interval, 1.5-10.0]; P = .008) compared with pathogen-negative cases. Although EPEC was identified in 3 of 21 (14%) healthy subjects by qPCR, the bacterial burden was low compared to patients with diarrhea (≤55 vs median, 6 × 104 bacteria/mg stool; P < .001). Among EPEC patients, the bacterial burden was higher in those who were immunosuppressed (median, 6.7 × 103 vs 55 bacteria/mg; P < .001) and those with fecal lifA/ifa-1 (median, 5 × 104 vs 120 bacteria/mg; P = .015). Response to antimicrobial therapy was seen in 44 of 48 (92%) patients with EPEC as the sole pathogen. Antimicrobial resistance was common and strains exhibited distinct patterns of adherence with variable cytotoxicity when studied in HIEs. Cancer care was delayed in 13% of patients.
Immunosuppressed cancer patients with EPEC-associated diarrhea carry high burden of EPEC with strains that are resistant to antibiotics, exhibit novel patterns of adherence when studied in HIEs, and interfere with cancer care.
肠致病性大肠杆菌(EPEC)作为癌症和免疫功能低下患者腹泻病因的作用存在争议。粪便细菌载量的定量分析已被提议作为区分定植患者与真正感染患者的一种方法。
我们研究了77例成年癌症和免疫抑制性腹泻患者,通过FilmArray在粪便中鉴定出EPEC,25例病原体阴性腹泻患者,以及21例无腹泻的健康成年人。通过定量聚合酶链反应(qRT-PCR)研究粪便中的EPEC基因eaeA和lifA/efa-1,并对菌株的毒力因子和对人肠道类器官(HIEs)的黏附特性进行表征。
与病原体阴性病例相比,EPEC患者更易发生社区获得性腹泻(比值比,3.82[95%置信区间,1.5 - 10.0];P = 0.008)。虽然通过qPCR在21名健康受试者中的3名(14%)中鉴定出EPEC,但与腹泻患者相比,细菌载量较低(≤55对中位数6×10⁴细菌/毫克粪便;P < 0.001)。在EPEC患者中,免疫抑制患者(中位数6.7×10³对55细菌/毫克;P < 0.001)和粪便中存在lifA/ifa-1的患者(中位数5×10⁴对120细菌/毫克;P = 0.015)的细菌载量更高。48例以EPEC为唯一病原体的患者中有44例(92%)对抗菌治疗有反应。抗菌药物耐药性很常见,菌株在HIEs中研究时表现出不同的黏附模式和可变的细胞毒性。13%的患者癌症治疗延迟。
免疫抑制的癌症患者发生EPEC相关腹泻时,EPEC载量高,菌株对抗生素耐药,在HIEs中研究时表现出新的黏附模式,并干扰癌症治疗。