Relationship between bacterial strain type, host biomarkers, and mortality in Clostridium difficile infection.

(See the Editorial Commentary by Gerding and Johnson on pages 1601–3.) The widespread emergence of hypervirulent polymerase chain reaction (PCR) ribotype 027/NAP1/BI/sequence type (ST) 1 [1] strains in the early 2000s [2, 3] substantially increased Clostridium difficile infection (CDI) incidence. PCR ribotype 027 has also been associated with more severe outcomes in most [2, 4, 5] but not all [6–9] studies. Outcome variation across non-027 strains has rarely been investigated, invariably with small numbers, although these now account for most new CDIs. One study [6] (n = 395) found significantly more complicated disease outcomes with PCR ribotypes 018 (ST 17 from [10]; n = 23) and 056 (ST 34/58 [10]; n = 6), whereas another [11] (n = 168) reported similar 30-day mortality in PCR ribotype-027 (n = 46) and 017 (ST 37 [10]; n = 57). Although PCR ribotype 078 (ST 11), common in livestock [12] and rising in incidence [6, 13], is denoted hypervirulent on the basis of increased toxin production [14] and individual case severity [15], supporting clinical data are few. Attributable mortality and severe diarrhea was similar in PCR ribotype 078 (n = 54) and 027 (n = 124) in 1 study (both greater than in 501 non-027/078 cases) [13], but PCR ribotype 078 (n = 31) was not associated with complicated CDI in another [6]. Although scores to predict CDI severity, complications, or recurrence have variably included biomarkers (eg, white blood count [WBC], C-reactive protein [CRP]) [16], no studies have investigated associations between CDI strains and biomarkers. We aimed therefore to investigate whether the genotype of C. difficile clinical isolates from multilocus sequence typing (MLST) was associated with mortality and severity biomarkers using a large population-based database of CDI cases and to explore associations between strain-specific effects on host biomarkers and mortality to provide insights into infection pathogenesis.