Recombinant C. difficile Toxin A

A 74-year-old male was referred to our critical care department for refractory severe watery diarrhea with advanced leukocytosis (over 70,000/ml) after multiple administrations of eradication therapy against Helicobacter pylori (HP). He was diagnosed as having fulminant colitis due to Clostridioides difficile after antimicrobial eradication therapy. He was given intravenous metronidazole and oral vancomycin. He also received supportive therapy including continuous hemodiafiltration for severe metabolic acidosis. However, despite emergency open sigmoidectomy, he died. The C. difficile isolate recovered was PCR-ribotype 002, which was positive for toxins A and B but negative for binary toxin. HP eradication therapy for prevention of chronic gastritis and stomach cancer is now in widespread use. Although such secondary severe complications are rare, we consider it to be necessary to pay sufficient attention when administering HP eradication therapy. (c) 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Purpose Existing clinical or microbiological scores are not sensitive enough to obtain prompt identification of patients at risk of complicated Clostridium difficile infection (CDI). Our aim was to use a CDI animal model to evaluate 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography ([F-18]FDG-PET) as a marker of severe course of infection. Procedures CDI was induced with cefoperazone for 10 days followed by clindamycin 1 day before C. difficile inoculation. Mice were divided into wild type (n = 6), antibiotic without infection (AC n = 4), h001-infected (n = 5, ribotype 001), and h027-infected (n = 5, ribotype 027). Two days after inoculation, [F-18]FDG-PET was acquired. Weight, general animal condition, and survival were monitored daily for 9 days. Results h001 group showed symptoms for 4 days with 0 % mortality and a similar colon uptake than control animals (h001 0.52 +/- 0.20, WT 0.42 +/- 0.07, and AC 0.36 +/- 0.06). The h027 group showed symptoms up to 7 days, with 66.7 % of mortality 4 days after infection, and significantly higher colon uptake (0.93 +/- 0.38, p < 0.05). Clinical score was associated to colon and cecum uptake (rho = 0.78, p = 0.0001) (rho = 0.73, p = 0.0003). Conclusion High toxin producer ribotype 027 induced more severe CDI infections, correlating with higher colon and cecum [F-18]FDG uptake. Colon uptake may purportedly serve as early predictor of CDI severity.