RESUMEN
BACKGROUND: Clostridium difficile is the leading cause of antibiotic-associated diarrhoea and is associated with an increase in morbidity and mortality. There is a wide variance in disease severity with some patients suffering a single, self-limiting episode of diarrhoea while others suffer more intractable problems with recurrent attacks or toxic dilatation. Numerous different C. difficile ribotypes exist, some of which are considered hypervirulent. The magnitude of toxin production alone is not sufficient to explain the varying virulence of these ribotypes, suggesting the involvement of other mechanisms. METHODS: To test the same patient's response to infection with different C. difficile ribotypes, we reviewed 45 patients who suffered two episodes of C. difficile infection and determined by ribotyping and MLVA whether the second episode was due to the same strain or a different strain. RESULTS: Patients harbouring a different strain had significantly higher C-reactive protein (CRP) responses on the first assessed infection (143 mg/L ± 20 vs. 55 ± 9.63, p = 0.0001) and a significantly lower CRP on reinfection (p = 0.048). Same strain patients had a non-significant increase in CRP response on second infection. CONCLUSIONS: This suggests that the inflammatory response to C. difficile is determined by an interaction between host immunobiology, previous exposure and C. difficile strain.
Asunto(s)
Proteína C-Reactiva/metabolismo , Clostridioides difficile/clasificación , Enterocolitis Seudomembranosa/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Clostridioides difficile/genética , Clostridioides difficile/aislamiento & purificación , Estudios de Cohortes , ADN Bacteriano/análisis , Enterocolitis Seudomembranosa/sangre , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Repeticiones de Minisatélite , Reacción en Cadena de la Polimerasa , Recurrencia , Estudios Retrospectivos , RibotipificaciónRESUMEN
Epidemic C. difficile (027/BI/NAP1) has rapidly emerged in the past decade as the leading cause of antibiotic-associated diarrhea worldwide. However, the key events in evolutionary history leading to its emergence and the subsequent patterns of global spread remain unknown. Here, we define the global population structure of C. difficile 027/BI/NAP1 using whole-genome sequencing and phylogenetic analysis. We show that two distinct epidemic lineages, FQR1 and FQR2, not one as previously thought, emerged in North America within a relatively short period after acquiring the same fluoroquinolone resistance-conferring mutation and a highly related conjugative transposon. The two epidemic lineages showed distinct patterns of global spread, and the FQR2 lineage spread more widely, leading to healthcare-associated outbreaks in the UK, continental Europe and Australia. Our analysis identifies key genetic changes linked to the rapid transcontinental dissemination of epidemic C. difficile 027/BI/NAP1 and highlights the routes by which it spreads through the global healthcare system.