In whole-genome sequencing (WGS) of a Clostridioides difficile outbreak investigation, 3 patients on the same ward have isolates with SNP (single nucleotide polymorphism) differences of ≤2. A fourth patient on a different ward has a contemporaneous isolate with ≥30 SNP differences from the cluster. What conclusion is appropriate?

• A The first three patients represent a clonal outbreak cluster; the fourth patient likely acquired C. difficile independently (no epidemiological link) ✓
• B All four patients share a common epidemiological source; SNP differences below 50 indicate same outbreak
• C WGS cannot distinguish outbreak-related strains for C. difficile; ribotyping is the only valid method
• D ≤2 SNP difference indicates the same patient source; ≥30 SNP confirms a laboratory contamination artefact

Explanation

In WGS-based outbreak investigation, SNP thresholds define clonal clustering. For C. difficile, isolates with ≤2 SNP differences are considered part of the same transmission cluster with high likelihood. The three ward patients with ≤2 SNP differences represent a nosocomial transmission cluster and warrant epidemiological investigation (common healthcare worker, environment, or equipment). The fourth patient with ≥30 SNPs has acquired a genetically distinct strain, suggesting independent acquisition. WGS has replaced or supplemented ribotyping for outbreak investigation as it provides higher resolution.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

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