Sambol Susan P, Skinner Andrew M, Serna-Perez Fidel, Owen Benjamin, Gerding Dale N, Johnson Stuart
Loyola University Medical Center, Department of Medicine, Maywood, Illinois, USA.
Edward Hines Jr., VA Hospital, Research Section, Infection Diseases Section, Hines, Illinois, USA.
Microbiol Spectr. 2023 Mar 28;11(2):e0051723. doi: 10.1128/spectrum.00517-23.
Colonization with nontoxigenic Clostridioides difficile strain M3 (NTCD-M3) has been demonstrated in susceptible hamsters and humans when administered after vancomycin treatment. NTCD-M3 has also been shown to decrease risk of recurrent C. difficile infection (CDI) in patients following vancomycin treatment for CDI. As there are no data for NTCD-M3 colonization after fidaxomicin treatment, we studied the efficacy of NTCD-M3 colonization and determined fecal antibiotic levels in a well-studied hamster model of CDI. Ten of 10 hamsters became colonized with NTCD-M3 after 5 days of treatment with fidaxomicin when NTCD-M3 was administered daily for 7 days after treatment discontinuation. The findings were nearly identical to 10 vancomycin-treated hamsters also given NTCD-M3. High fecal levels of OP-1118, the major fidaxomicin metabolite, and vancomycin were noted during treatment with the respective agents and modest levels noted 3 days after treatment discontinuation at the time when most of the hamsters became colonized. These findings support the ongoing development of NTCD-M3 for the prevention of recurrent CDI. NTCD-M3 is a novel live biotherapeutic, that has been shown in a Phase 2 clinical trial to prevent recurrence of C. difficile infection (CDI) when administered shortly after antibiotic treatment of the initial CDI episode. Fidaxomicin was not, however, in widespread use at the time this study was conducted. A large multi-center Phase 3 clinical trial is now currently in the planning stage, and it is anticipated that many patients eligible for this study will be treated with fidaxomicin. Since efficacy in the hamster model of CDI has predicted success in patients with CDI, we studied the ability of NTCD-M3 to colonize hamsters after treatment with either fidaxomicin or vancomycin.
非产毒艰难梭菌菌株M3（NTCD-M3）在易感仓鼠和人类中，于万古霉素治疗后给药时已被证明可实现定植。NTCD-M3还被证明可降低万古霉素治疗艰难梭菌感染（CDI）的患者中复发性CDI的风险。由于没有关于非达霉素治疗后NTCD-M3定植的数据，我们在一个经过充分研究的CDI仓鼠模型中研究了NTCD-M3定植的疗效，并测定了粪便中的抗生素水平。在非达霉素治疗5天后，当NTCD-M3在停药后每日给药7天时，10只仓鼠中有10只被NTCD-M3定植。这些结果与10只也接受NTCD-M3治疗的万古霉素治疗仓鼠几乎相同。在用各自药物治疗期间，观察到粪便中主要的非达霉素代谢物OP-1118和万古霉素水平较高，在停药3天后，当大多数仓鼠定植时，观察到适度水平。这些发现支持了NTCD-M3在预防复发性CDI方面的持续研发。NTCD-M3是一种新型的活生物治疗剂，在2期临床试验中已显示，在初始CDI发作的抗生素治疗后不久给药时，可预防艰难梭菌感染（CDI）的复发。然而，在本研究进行时，非达霉素并未广泛使用。一项大型多中心3期临床试验目前正处于规划阶段，预计许多符合该研究条件的患者将接受非达霉素治疗。由于CDI仓鼠模型中的疗效已预测了CDI患者的成功，我们研究了NTCD-M3在接受非达霉素或万古霉素治疗后在仓鼠中定植的能力。
