Microbial and Inflammatory Markers for Fatal Clostridium difficile Associated Diarrhea
With its rising mortality rate in C. difficile infection (CDI), understanding the microbial factors and host inflammatory response associated with fatal infection is of public health importance. We hypothesize that subjects with fatal compared with treatment-responsive CDI are different in terms of host fecal inflammatory markers and toxin type of infecting C. difficile strain.
Between June 2011 and March 2013 in a teaching hospital in Texas Medical Center, a prospective study of all consenting CDI subjects identified 34 fatal cases. Patients in a comparison group consisted of the next subjects enrolled in the study without fatality (N=34). All participates submitted a diarrheal stool that was C. difficile cytotoxin B positive. Aliquots of the original stool sample were tested for interleukin (IL)-8.
Twenty-four of 34 (71%) fatal cases died within 10 weeks of onset of CDI. The number of patients with detectable fecal IL-8 concentration for the fatal cases was 12/34 (35%) compared with the non-fatal controls that were positive for IL-8 in 8/34 (24%). The mean value of fecal IL-8 in the fatal group was 940.62±1001.66pg/mL compared with 185.24±592.39pg/Ml for the non-fatal subjects (p=0.094). Eleven of 21 patients with fatal outcome within 10 weeks of CDI had detectable fecal IL-8 with a mean concentration of 511.17±1168.38pg/mL; statistically higher than in the controls (p=0.04).
Presence of tcdC deletion in C. difficile isolates from patients with fatal CDI (13/34=38%) was statistically higher than found with controls (5/34=15%, p=0.02). Patients who died within 10 weeks of onset CDI had higher prevalence of tcdC deletion (13/24=54%) than patients who survived more than 10 weeks (p=0.007).
Host and microbial factors are important in the fatal outcome in CDI. Patients who had a fatal outcome more often had stools positive for IL-8 and had increased concentrations of fecal IL-8 compared with non-fatal CDAD. Fatal cases of CDAD more often were infected by a potentially hypervirulent strain of C. difficile positive for tcdC deletion. The differences seemed particularly striking when looking at the group who expired within 10 weeks of a CDI diagnosis, probably more indicative of CDAD-associated mortality than the patients showing more remote fatality.
Z. D. Jiang,
T. M. Lasco, None
H. Dupont, None