Contribution to Clostridium Difficile Transmission of Symptomatic Patients With Toxigenic Strains Who Are Fecal Toxin Negative.
The role of symptomatic patients who are toxigenic strain positive (TS+) but fecal toxin negative (FT-) in transmission of Clostridium difficile is currently unknown.



We investigated the contribution of symptomatic TS+/FT- and TS+/FT+ patients in C. difficile transmission in 2 UK regions. From 2-step testing, all glutamate dehydrogenase (GDH)-positive specimens, regardless of fecal toxin result, from Oxford (April 2012 through April 2013) and Leeds (July 2012 through April 2013) microbiology laboratories underwent culture and whole-genome sequencing (WGS), using WGS to identify toxigenic strains. Plausible sources for each TS+/FT+ case, including TS+/FT- and TS+/FT+ patients, were determined using WGS, with and without hospital admission data.



A total of 1447 of 12772 (11%) fecal samples were GDH positive, 866 of 1447 (60%) contained toxigenic C. difficile, and fecal toxin was detected in 511 of 866 (59%), representing 235 Leeds and 191 Oxford TS+/FT+ cases. TS+/FT+ cases were 3 times more likely to be plausibly acquired from a previous TS+/FT+ case than a TS+/FT- patient. Fifty-one of 265 (19%) TS+/FT+ cases diagnosed >3 months into the study were genetically related (≤2 single-nucleotide polymorphisms) to ≥1 previous TS+/FT+ case or TS+/FT- patient: 27 (10%) to only TS+/FT+ cases, 9 (3%) to only TS+/FT- patients, and 15 (6%) to both. Only 10 of 265 (4%) were genetically related to a previous TS+/FT+ or TS+/FT- patient and shared the same ward simultaneously or within 28 days.



Symptomatic TS+/FT- patients were a source of C. difficile transmission, although they accounted for less onward transmission than TS+/FT+ cases. Although transmission from symptomatic patients with either fecal toxin status accounted for a low overall proportion of new cases, both groups should be infection control targets.
Department of Microbiology, Leeds Teaching Hospitals NHS Trust, UK.
Damian P C
DPC
Mawer
Nuffield Department of Medicine, University of Oxford, UK.|National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, UK.
David W
DW
Eyre
Nuffield Department of Medicine, University of Oxford, UK.|National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, UK.
David
D
Griffiths
Department of Microbiology, Leeds Teaching Hospitals NHS Trust, UK.|Leeds Regional Microbiology Laboratory, Public Health England, UK.
Warren N
WN
Fawley
Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, UK.
Jessica S H
JSH
Martin
Nuffield Department of Medicine, University of Oxford, UK.|National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, UK.
T Phuong
TP
Quan
Nuffield Department of Medicine, University of Oxford, UK.|National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, UK.
Timothy E A
TEA
Peto
Nuffield Department of Medicine, University of Oxford, UK.|National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, UK.|Public Health England, Colindale, United Kingdom.
Derrick W
DW
Crook
Nuffield Department of Medicine, University of Oxford, UK.|National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford, UK.
A Sarah
AS
Walker
Department of Microbiology, Leeds Teaching Hospitals NHS Trust, UK.|Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, UK.
Mark H
MH
Wilcox
D000368:Aged; D000369:Aged, 80 and over; D001427:Bacterial Toxins / Q000032:analysis*; D001431:Bacteriological Techniques; D016360:Clostridioides difficile / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D003015:Clostridium Infections / Q000453:epidemiology / Q000473:pathology / Q000635:transmission*; D018562:Disease Transmission, Infectious; D005243:Feces / Q000737:chemistry* / Q000382:microbiology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D058889:Molecular Typing; D017422:Sequence Analysis, DNA; D006113:United Kingdom / Q000453:epidemiology
D001427:Bacterial Toxins
Clostridium difficile; fecal toxin; infection; transmission