In the Endemic Setting, Clostridium difficile Ribotype 027 Is Virulent But Not Hypervirulent

Abstract

BACKGROUND Conflicting reports have been published on the association between Clostridium difficile ribotypes and severe disease outcomes in patients with C. difficile infection (CDI); several so-called hypervirulent ribotypes have been described. We performed a multicenter study to assess severe disease presentation and severe outcomes among CDI patients infected with different ribotypes. METHODS Stool samples that tested positive for C. difficile toxin were collected and cultured from patients who presented to any of 7 different hospitals in Houston, Texas (2011–2013). C. difficile was characterized using a fluorescent PCR ribotyping method. Medical records were reviewed to determine clinical characteristics and ribotype association with severe CDI presentation (ie, leukocytosis and/or hypoalbuminemia) and severe CDI outcomes (ie, ICU admission, ileus, toxic megacolon, colectomy, and/or in-hospital death). RESULTS Our study included 715 patients aged 61 ± 18 years (female: 63%; median Charlson comorbidity index: 2.5 ± 2.4; hospital-onset CDI: 45%; severe CDI: 36.7%; severe CDI outcomes: 12.3%). The most common ribotypes were 027, 014-020, FP311, 002, 078-126, and 001. Ribotype 027 was a significant independent predictor of severe disease (adjusted odds ratio [aOR], 2.24; 95% confidence interval [CI], 1.53–3.29; P < .001) and severe CDI outcomes (aOR, 1.71; 95% CI, 1.02–2.85; P = .041) compared with all other ribotypes in aggregate. However, in an analysis using all common ribotypes as individual variables, ribotype 027 was not associated with severe CDI outcomes more often than other ribotypes. CONCLUSION Ribotype 027 showed virulence equal to that of other ribotypes identified in this endemic setting. Clinical severity markers of CDI may be more predictive of severe CDI outcomes than a particular ribotype.

PCR ribotypes of Clostridioides difficile across Texas from 2011 to 2018 including emergence of ribotype 255

“…[32] Our cohort study indicated disease severity and outcomes similar to those seen with ribotype 014-020, but was limited by sample size. Additionally, ribotype 255 was correlated with much lower odds of severe CDI compared to ribotype 027 [22]. Patients infected with ribotype 027 were older and with more comorbidities compared to those infected with ribotype 255, potentially indicating a bias in who is infected with each ribotype.…”

“…Samples were plated onto selective cefoxitin-cycloserine-fructose agar (CCFA) plates (Anaerobe Systems, Morgan Hill, CA) and anaerobically incubated for 48-72 h for culture. Characteristic C. difficile colonies were tested using latex agglutination reagent (Oxoid, Hampshire, England) and presence of triose phosphate isomerase and toxin genes was determined using multiplex PCR [22]. Fluorescent PCR ribotyping was performed as previously described [23].…”

Control of Clostridium difficile Infection by Defined Microbial Communities

“…However, some “hypervirulent” attributes of ribotype 027 vary across strains (e.g., degree of toxin production and sporulation (22)) or are found in ribotypes not typically associated with increased disease severity (e.g., fluoroquinolone resistance (23)), making it difficult to pinpoint specific mechanisms responsible for increased incidence and/or severity of infection with ribotype 027 strains. Correspondingly, some clinical studies (24-26) failed to reproduce statistically significant increases in severe CDI in patients infected with ribotype 027 observed in other studies (13, 27, 28). Finally, even as the frequency of ribotype 027-associated CDI has stabilized or decreased in some regions (29, 30), the overall frequency of CDI has remained high, with other C. difficile ribotypes increasing in prevalence (29- 32).…”

To Lump or To Split: Does Strain Lineage for Clostridioides difficile Matter?

“…In a similar study of 715 CDI patients in 7 hospitals in Houston, TX, ribotype 027 strain CDI (23.8% of total cases) was an independent predictor of both severe CDI and severe outcome CDI (adjusted odds ratios of 2.24 and 1.71, respectively) when considering a comparison to all other CDI case ribotypes in aggregate (10). No logistic regression model was able to establish any single ribotype as a significant predictor for severe CDI or outcome; in fact, 3 other non-027 ribotypes had point estimates of severe CDI outcome as high as or higher than ribotype 027 in this study (10). A European study noted that ribotype 078 CDI had higher observed mortality than other lineages, including ribotype 027 (11).…”

“…In a single-center cross-sectional study of 743 CDI patients in Michigan, ribotype 027 was associated with severe CDI in an unadjusted analysis, but this ribotype was not associated with severe CDI when considering 11 other covariates; only leukocytosis and serum albumin level were associated with severe CDI in an adjusted logistic regression model (9). In a similar study of 715 CDI patients in 7 hospitals in Houston, TX, ribotype 027 strain CDI (23.8% of total cases) was an independent predictor of both severe CDI and severe outcome CDI (adjusted odds ratios of 2.24 and 1.71, respectively) when considering a comparison to all other CDI case ribotypes in aggregate (10). No logistic regression model was able to establish any single ribotype as a significant predictor for severe CDI or outcome; in fact, 3 other non-027 ribotypes had point estimates of severe CDI outcome as high as or higher than ribotype 027 in this study (10).…”