Patient and Strain Characteristics Associated With Clostridium difficile Transmission and Adverse Outcomes

BACKGROUND: No study has used whole-genome sequencing (WGS) to investigate risk factors for Clostridium difficile (CD) transmission between cases, or assessed the impact of recent acquisition on patient outcome. METHODS: This 20 month retrospective cohort study included consecutive cytotoxin-positive diarrheal samples, which 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. RESULTS: Of 660 CD cases, 640 (97%) were sequenced, of which 567 (89%) shared a ribotype with a prior case, but only 227 (35%) were ≤2 SNVs from a prior case, supporting recent acquisition. Plausible (<2 SNVs) recent ward-based acquisition from a symptomatic case 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 < .05) for CD acquisition included older age, longer inpatient duration, and ribotype; these factors, and male sex, increased onward transmission. Patients with a plausible donor had a greater risk of recurrence (adjusted P = .001) and trended towards greater 30-day mortality (adjusted P = .06). Ribotype had no additional mortality or recurrence impact after adjusting for acquisition (P > .1). CONCLUSIONS: 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 associated with increased healthcare-associated CD transmission could be used to target preventative interventions.