Patient and strain characteristics associated with Clostridium difficile transmission and adverse outcomes.
Martin JSH., Eyre DW., Fawley WN., Griffiths D., Davies K., Mawer DPC., Peto TEA., Crook DW., Walker AS., Wilcox MH.
No previous study has used whole-genome sequencing (WGS) to investigate risk factors for C. difficile(CD) transmission between symptomatic cases, or assessed the impact of recent acquisition on patient outcome.This retrospective cohort study included consecutive diarrhoeal samples positive by cytotoxin assay in Leeds, UK(Aug10-Apr12). All samples underwent culture, ribotyping and WGS(Illumina). Sequenced isolates were compared using single nucleotide variants(SNVs). Independent predictors of acquisition from another case, onward transmission, 120-day recurrence and 30-day mortality were identified using logistic regression with backwards elimination.640/660(97·0%) CD cases were sequenced. 567(89%) cases shared a ribotype with a prior case but only 227(35%) were ≤2 SNVs from a prior case, supporting recent acquisition. Plausible recent ward-based acquisition from a symptomatic case <2 SNVs was more frequent in certain ribotypes; 64%(67/105) for ribotype-027 cases, compared with 11%(6/57) for ribotype-078. Independent risk factors (adjusted p<0·05) for CD acquisition included older age, longer inpatient duration and ribotype; these factors, and male gender, increased onward transmission. Patients with a plausible donor (≤2 SNVs) had a greater risk of recurrence (adjusted p=0·001) and trend towards greater 30-day mortality (adjusted p=0·06). There was no additional impact of ribotype on mortality or recurrence after adjusting for the stronger impact of acquisition itself (p>0·1).Greater transmission of certain lineages suggests CD may have different reservoirs and modes of transmission. Acquiring CD from a recent case is associated with poorer clinical outcomes. Clinical characteristics shown to be associated with increased healthcare-associated CD transmission could be used to target preventative interventions.