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. 2017 May 1;64(9):1163-1170.
doi: 10.1093/cid/cix079.

Contribution to Clostridium Difficile Transmission of Symptomatic Patients With Toxigenic Strains Who Are Fecal Toxin Negative

Damian P C Mawer  1 , David W Eyre  2   3 , David Griffiths  2   3 , Warren N Fawley  1   4 , Jessica S H Martin  5 , T Phuong Quan  2   3 , Timothy E A Peto  2   3 , Derrick W Crook  2   3   6 , A Sarah Walker  2   3 , Mark H Wilcox  1   5
Affiliations

Contribution to Clostridium Difficile Transmission of Symptomatic Patients With Toxigenic Strains Who Are Fecal Toxin Negative

Damian P C Mawer et al. Clin Infect Dis. .

Abstract

Background: The role of symptomatic patients who are toxigenic strain positive (TS+) but fecal toxin negative (FT-) in transmission of Clostridium difficile is currently unknown.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Clostridium difficile; fecal toxin; infection; transmission.

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Figures

Figure 1.
Figure 1.
Samples and patient demographics for Leeds (A) and Oxfordshire (B). Each percentage uses the row above as denominator. Distinct infection is >10 single-nucleotide polymorphisms distinct to any previous infection in the same patient. Age and sex were not recorded for 3 Oxfordshire patients. Abbreviations: CA, community-associated; EIA, enzyme immunoassay; GDH, glutamate dehydrogenase; HA, healthcare-associated; IQR, interquartile range; MALDI-TOF MS, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; QC, quality control; UK, United Kingdom; WGS, whole-genome sequencing.
Figure 2.
Figure 2.
Numbers of patients in clusters related within ≤2 single-nucleotide polymorphisms (SNPs). Clusters consisting exclusively of patients with toxigenic strain–positive, fecal toxin-negative (TS+/FT–) Clostridium difficile infection (CDI) are shown in blue, clusters consisting exclusively of TS+/FT+ cases in red, and clusters with both TS+/FT– patients and TS+/FT+ cases in orange.
Figure 3.
Figure 3.
Proportion of Leeds and Oxfordshire Clostridium difficile infection (CDI) cases genetically related to a previous toxigenic strain–positive, fecal toxin-positive (TS+/FT+) case or TS+/FT– patient within varying single-nucleotide polymorphism thresholds. Bars are shaded according to the fecal toxin status of the genetically related potensal sources of infection.
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Comment in

  • Diagnosing an Infection Control Risk.
    Kutty PK, McDonald LC. Kutty PK, et al. Clin Infect Dis. 2017 May 1;64(9):1171-1173. doi: 10.1093/cid/cix085. Clin Infect Dis. 2017. PMID: 28158635 Free PMC article. No abstract available.

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