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Fidaxomicin Inhibits Clostridium difficile Toxin A-Mediated Enteritis in the Mouse Ileum
- Source :
- Antimicrobial agents and chemotherapy, vol 58, iss 8, Koon, HW; Ho, S; Hing, TC; Cheng, M; Chen, X; Ichikawa, Y; et al.(2014). Fidaxomicin inhibits Clostridium difficile toxin a-mediated enteritis in the mouse ileum. Antimicrobial Agents and Chemotherapy, 58(8), 4642-4650. doi: 10.1128/AAC.02783-14. UCLA: Retrieved from: http://www.escholarship.org/uc/item/7vp4b3kd
- Publication Year :
- 2014
- Publisher :
- American Society for Microbiology, 2014.
-
Abstract
- Clostridium difficile infection (CDI) is a common, debilitating infection with high morbidity and mortality. C. difficile causes diarrhea and intestinal inflammation by releasing two toxins, toxin A and toxin B. The macrolide antibiotic fidaxomicin was recently shown to be effective in treating CDI, and its beneficial effect was associated with fewer recurrent infections in CDI patients. Since other macrolides possess anti-inflammatory properties, we examined the possibility that fidaxomicin alters C. difficile toxin A-induced ileal inflammation in mice. The ileal loops of anesthetized mice were injected with fidaxomicin (5, 10, or 20 μM), and after 30 min, the loops were injected with purified C. difficile toxin A or phosphate-buffered saline alone. Four hours after toxin A administration, ileal tissues were processed for histological evaluation (epithelial cell damage, neutrophil infiltration, congestion, and edema) and cytokine measurements. C. difficile toxin A caused histologic damage, evidenced by increased mean histologic score and ileal interleukin-1β (IL-1β) protein and mRNA expression. Treatment with fidaxomicin (20 μM) or its primary metabolite, OP-1118 (120 μM), significantly inhibited toxin A-mediated histologic damage and reduced the mean histology score and ileal IL-1β protein and mRNA expression. Both fidaxomicin and OP-1118 reduced toxin A-induced cell rounding in human colonic CCD-18Co fibroblasts. Treatment of ileal loops with vancomycin (20 μM) and metronidazole (20 μM) did not alter toxin A-induced histologic damage and IL-1β protein expression. In addition to its well known antibacterial effects against C. difficile , fidaxomicin may possess anti-inflammatory activity directed against the intestinal effects of C. difficile toxins.
- Subjects :
- Male
Messenger
Interleukin-1beta
Anti-Inflammatory Agents
Gene Expression
Injections, Intralesional
Inbred C57BL
medicine.disease_cause
Mice
Enterotoxins
Intestinal mucosa
Edema
Pharmacology (medical)
Fidaxomicin
Intestinal Mucosa
Enterocolitis, Pseudomembranous
Enterocolitis
Pseudomembranous
Pharmacology and Pharmaceutical Sciences
Clostridium difficile
Anti-Bacterial Agents
Intralesional
Infectious Diseases
Neutrophil Infiltration
Medical Microbiology
Vancomycin
medicine.symptom
medicine.drug
Bacterial Toxins
Clostridium difficile toxin A
Biology
Microbiology
Injections
Ileum
Metronidazole
medicine
Animals
Experimental Therapeutics
RNA, Messenger
Pharmacology
Clostridioides difficile
Toxin
Epithelial Cells
Fibroblasts
Mice, Inbred C57BL
Aminoglycosides
RNA
Subjects
Details
- ISSN :
- 10986596 and 00664804
- Volume :
- 58
- Database :
- OpenAIRE
- Journal :
- Antimicrobial Agents and Chemotherapy
- Accession number :
- edsair.doi.dedup.....fa812d3865cd61c8d19c638a7cb36e1d