Gastrointestinal localization of metronidazole by a lactobacilli-inspired tetramic acid motif improves treatment outcomes in the hamster model ofClostridium difficileinfection | Zendy

Philip Cherian | Zendy; Xiaoqian Wu | Zendy; Lei Yang | Zendy; Jerrod Scarborough | Zendy; Aman P. Singh | Zendy; Zahidul A. Alam | Zendy; Richard Lee | Zendy; Julian G. Hurdle | Zendy

Open Access

Gastrointestinal localization of metronidazole by a lactobacilli-inspired tetramic acid motif improves treatment outcomes in the hamster model ofClostridium difficileinfection

Author(s) -

Philip Cherian,

Xiaoqian Wu,

Lei Yang,

Jerrod Scarborough,

Aman P. Singh,

Zahidul A. Alam,

Richard Lee,

Julian G. Hurdle

Publication year - 2015

Publication title -

journal of antimicrobial chemotherapy

Language(s) - English

Resource type - Journals

eISSN - 1460-2091

pISSN - 0305-7453

DOI - 10.1093/jac/dkv231

Subject(s) - metronidazole , lactobacillus reuteri , clostridium difficile , microbiology and biotechnology , pharmacokinetics , antibiotics , hamster , gastrointestinal tract , medicine , lactobacillus , biology , pharmacology , bacteria , genetics

Metronidazole, a mainstay treatment for Clostridium difficile infection (CDI), is often ineffective for severe CDI. Whilst this is thought to arise from suboptimal levels of metronidazole in the colon due to rapid absorption, empirical validation is lacking. In contrast, reutericyclin, an antibacterial tetramic acid from Lactobacillus reuteri, concentrates in the gastrointestinal tract. In this study, we modified metronidazole with reutericyclin's tetramic acid motif to obtain non-absorbed compounds, enabling assessment of the impact of pharmacokinetics on treatment outcomes.

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