Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital/CSIC/University of Seville, 41013 Seville, Spain.
CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Int J Mol Sci. 2024 Sep 30;25(19):10550. doi: 10.3390/ijms251910550.
We evaluated the efficacy of the adoptive transfer of memory B, CD4+, and CD8+ T lymphocytes compared with sulbactam and tigecycline in an experimental murine pneumonia model by two multidrug-resistant strains, colistin-susceptible AbCS01 and colistin-resistant AbCR17. Pharmacodynamically optimized antimicrobial dosages were administered for 72 h, and intravenous administration of 2 × 10 of each of the memory cells in a single dose 30 min post-infection. Bacterial lung and blood counts and mortality rates were analyzed. Results showed that a single dose of memory B or CD4+ T cells was as effective as sulbactam in terms of bacterial clearance from the lungs and blood compared with the untreated mice or the tigecycline-treated mice inoculated with the AbCS01 strain. In the pneumonia model by AbCR17, a single dose of memory B or CD4+ T cells also reduced the bacterial load in the lungs compared with both antibiotic groups and was more efficacious than tigecycline in terms of blood clearance. Regarding survival, the adoptive transfer of memory B or CD4+ T cells was as effective as three days of sulbactam treatment for both strains. These data suggest that adoptive memory cell transfer could be a new effective treatment of multidrug-resistant infections.
我们评估了在实验性肺炎模型中，与舒巴坦和替加环素相比，过继转移记忆 B、CD4+和 CD8+T 淋巴细胞的疗效，该模型使用了两种多药耐药菌株，即对黏菌素敏感的 AbCS01 和对黏菌素耐药的 AbCR17。对药效学优化的抗菌剂量进行了 72 小时的治疗，并在感染后 30 分钟内单次静脉给予 2×10 个每种记忆细胞。分析了细菌肺部和血液计数以及死亡率。结果表明，与未治疗的小鼠或接种 AbCS01 株的替加环素治疗的小鼠相比，单次剂量的记忆 B 或 CD4+T 细胞在清除肺部和血液中的细菌方面与舒巴坦一样有效。在 AbCR17 引起的肺炎模型中，与两种抗生素组相比，单次剂量的记忆 B 或 CD4+T 细胞也减少了肺部的细菌负荷，并且在清除血液中的细菌方面比替加环素更有效。关于生存，过继转移记忆 B 或 CD4+T 细胞与舒巴坦治疗三天对两种菌株同样有效。这些数据表明，过继性记忆细胞转移可能是治疗多药耐药感染的一种新的有效方法。
