van Opstal Edward, Kolling Glynis L, Moore John H, Coquery Christine M, Wade Nekeithia S, Loo William M, Bolick David T, Shin Jae Hyun, Erickson Loren D, Warren Cirle A
Department of Biology, Vanderbilt University, Nashville, Tennessee.
Department of Medicine.
J Infect Dis. 2016 Jul 1;214(1):130-9. doi: 10.1093/infdis/jiw071. Epub 2016 Feb 24.
The elderly host is highly susceptible to severe disease and treatment failure in Clostridium difficile infection (CDI). We investigated how treatment with vancomycin in the aged host influences systemic and intestinal humoral responses and select intestinal microbiota.
Young (age, 2 months) and aged (age, 18 months) C57BL/6 mice were infected with VPI 10463 after exposure to broad-spectrum antibiotics. Vancomycin was given 24 hours after infection, and treatment was continued for 5 days. At select time points, specimens of serum and intestinal tissue and contents were collected for histopathologic analysis, to measure antibody levels and the pathogen burden, and to determine the presence and levels of select intestinal microbiota and C. difficile toxin.
Levels of disease severity, relapse, and mortality were increased, and recovery from infection was slower in aged mice compared to young mice. Serum levels of immunoglobulin M, immunoglobulin A, and immunoglobulin G against C. difficile toxin A were depressed in aged mice, and vancomycin treatment reduced antibody responses in both age groups. While baseline levels of total bacterial load, Bacteroidetes, Firmicutes, and Enterobacteriaceae were mostly similar, aged mice had a significant change in the Firmicutes to Bacteroidetes ratio with vancomycin treatment.
Vancomycin treatment decreases the systemic humoral response to CDI. Increased mortality from and recurrence of CDI in the aged host are associated with an impaired humoral response and a greater susceptibility to vancomycin-induced alteration of intestinal microbiota.
老年宿主在艰难梭菌感染（CDI）中极易发生重症疾病和治疗失败。我们研究了老年宿主中万古霉素治疗如何影响全身和肠道的体液反应以及特定肠道微生物群。
将年轻（2个月龄）和老年（18个月龄）的C57BL/6小鼠在接触广谱抗生素后感染VPI 10463。感染后24小时给予万古霉素，并持续治疗5天。在选定的时间点，收集血清、肠道组织和内容物标本进行组织病理学分析，以测量抗体水平和病原体负荷，并确定特定肠道微生物群和艰难梭菌毒素的存在及水平。
与年轻小鼠相比，老年小鼠的疾病严重程度、复发率和死亡率增加，感染恢复较慢。老年小鼠中针对艰难梭菌毒素A的免疫球蛋白M、免疫球蛋白A和免疫球蛋白G的血清水平降低，万古霉素治疗降低了两个年龄组的抗体反应。虽然总细菌负荷、拟杆菌门、厚壁菌门和肠杆菌科的基线水平大多相似，但万古霉素治疗后老年小鼠的厚壁菌门与拟杆菌门比例有显著变化。
万古霉素治疗会降低对CDI的全身体液反应。老年宿主中CDI死亡率增加和复发与体液反应受损以及对万古霉素诱导的肠道微生物群改变更易感性有关。
