Cristian Hernández-Rocha

Epidemic Clostridium difficile Ribotype 027 in Chile

To the Editor: The increased severity of Clostridium difficile infection is primarily attributed to the appearance of an epidemic strain characterized as PCR ribotype 027 (1). The only report that identified epidemic C. difficile ribotype 027 in an American country outside of North America comes from Costa Rica, raising the possibility that strains 027 might also be present in other countries of Latin America (2). Several studies between 2001 and 2009 have been conducted in South American countries to detect the incidence of C. difficile infection in hospitalized patients, but they did not identify which C. difficile strains were causing these infections (3).

Infecciones causadas por Clostridium difficile: una visión actualizada

Resumen de manejo de la infeccion asociada a C. dif fi cile (IACD) durante el primer episodio y recurrencias. SNG: sonda nasogastrica. TMF: trasplante de microbiota fecal. IV: intravenoso.Cuadro clinico compatible y estudio de laboratorio positivoCategorizar segun gravedadLeve o moderado Grave ComplicadoMetronidazol oral 500 mg c/8 horasVancomicina oral 125 mg c/6 horas Vancomicina oral o por SNG 500 mg c/6 horas + Metronidazol 500 mg c/8 horas ivSi existe ileo: agregar vancomicina intracolonica 500 mg c/4 a 6 horasConsiderar colectomiaRecurrencia de IACD (1a recurrencia)Tratar segun gravedad de episodio actualRecurrencia de IACD (2a recurrencia)Vancomicina en pulso o dosis decrecienteRecurrencia de IACD (3a recurrencia)Considerar TMF de acuerdo aceptabilidad del paciente, inmunoglobulina iv, rifaximina o fidaxomicina Tratamiento de IACD El tratamiento de IACD dependera de si se trata del primer, segundo o tercer episodio de IACD y de su gra-vedad, la cual se defi ne segun los parametros senalados previamente (Figura 4)

Prospective comparison of a commercial multiplex real-time polymerase chain reaction and an enzyme immunoassay with toxigenic culture in the diagnosis of Clostridium difficile–associated infections ☆

Clostridium difficile infections (CDI) is a leading cause of nosocomial infections worldwide. The changes in the epidemiology of CDI during the past years, including the appearance of new epidemic strains of C. difficile that cause CDI episodes with increased severity, have led to the development of molecular methods with improved sensitivity and specificity. This study was designed to compare the performances of one antigen assay (Vidas, bioMérieux) and one molecular assay (GeneXpert, Cepheid). Fecal specimens from hospitalized patients (n = 230) suspected of having CDI were tested by both assays. Eleven specimens were positive and 202 were negative for both methods. After discrepant analysis by C. difficile toxigenic culture with broth enrichment and neutralization assay, the total numbers of stool specimens classified as positive and negative for toxigenic C. difficile were 23 (10%) and 206 (89.6%), respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value for GeneXpert were 91.7%, 99%, 91.7%, and 99%, and for Vidas were 48%, 99%, 84.6%, and 94.5%, respectively. The sensitivity and PPV of polymerase chain reactoin GeneXpert assay far exceeded those of the EIA Vidas assay. The clinical characteristics of concordant and discrepant study patients were similar with the exception of the number of previous CDI episodes, which were higher in the concordant study patients; the clinical characteristics of both groups were similar. In conclusion, due to the appearance of more virulent strains of C. difficile during the last years that have produced dramatic changes in the epidemiology of C. difficile, we recommend that toxin enzyme immunoassays be replaced with rapid molecular-based tests for toxigenic C. difficile.

Predominance of Clostridium difficile ribotypes 012, 027 and 046 in a university hospital in Chile, 2012

In a 1-year survey at a university hospital we found that 20·6% (81/392) of patients with antibiotic associated diarrohea where positive for C. difficile. The most common PCR ribotypes were 012 (14·8%), 027 (12·3%), 046 (12·3%) and 014/020 (9·9). The incidence rate was 2·6 cases of C. difficile infection for every 1000 outpatients.

Outcome of relapsing Clostridium difficile infections do not correlate with virulence-, spore- and vegetative cell-associated phenotypes

One of the main clinical challenges of Clostridium difficile infections (CDI) is the high rate of relapse episodes. The main determinants involved in relapse of CDI include the presence of antibiotic-resistant C. difficile spores in the colonic environment and a permanent state of dysbiosis of the microbiota caused by antibiotic therapy. A possible scenario is that phenotypes related to the persistence of C. difficile spores might contribute to relapsing infections. In this study, 8 C. difficile isolates recovered from 4 cases with relapsing infection, and 9 isolates recovered from single infection cases were analyzed for PCR ribotyping and the presence of tcdA, tcdB and cdtAB genes. Factors associated to spore persistence, sporulation, spore adherence and biofilm formation and sporulation during biofilm formation were characterized. We also evaluated motility and cytotoxicity. However, we observed no significant difference in the analyzed phenotypes among the different clinical outcomes, most likely due to the high variability observed among strains within clinical backgrounds in each phenotype and the small sample size. It is noteworthy that C. difficile spores adhered to similar extents to undifferentiated and differentiated Caco-2 cells. By contrast, spores of all clinical isolates tested had increased germination efficiency in presence of taurocholate, while decreased sporulation rate during biofilm development in the presence of glucose. In conclusion, these results show that, at least in this cohort of patients, the described phenotypes are not detrimental in the clinical outcome of the disease.

Esporas de Clostridium difficile y su relevancia en la persistencia y transmisión de la infección

Resumen Clostridium difficile es un patogeno anaerobio, forma-dor de esporas y el agente etiologico mas importante de las diarreas asociadas a antimicrobianos, tanto nosocomiales como adquiridas en la comunidad. Las infecciones asocia-das a C. difficile poseen una elevada tasa de morbilidad en paises desarrollados y en vias de desarrollo. Los dos factores de virulencia principales son TcdA y TcdB, toxinas que causan la remodelacion del citoesqueleto lo cual desencadena los sintomas clinicos asociados a esta enfermedad infecciosa. A pesar que las esporas de C. difficile son el principal vehiculo de infeccion, persistencia en el hospedero y de transmision, pocos estudios se han enfocado sobre este clave aspecto. Es altamente probable que la espora juegue roles esenciales en los episodios de recurrencia y de transmision horizontal de la infeccion por este microorganismo. Estudios recientes han reve-lado caracteristicas unicas de las esporas de C. difficile que las hacen capaces de ser altamente transmisibles y persistir dentro del hospedero. Mas aun, algunas de estas propiedades estan relacionadas con la resistencia de sus esporas a los desinfectantes mas comunmente usados en los recintos hospitalarios. La presente revision resume los conocimientos mas relevantes en la biologia de las esporas de C. difficile, con un enfasis en aquellos aspectos con implicancias clinicas, incluido el control de infecciones en el ambiente hospitalario.

Diagnóstico y manejo de colitis ulcerosa grave: Una mirada actualizada

Ulcerative Colitis (UC) is a chronic inflammatory disease involving the colon, with alternating periods of remission and activity. Exacerbations can be severe and associated with complications and mortality. Diagnosis of severe UC is based on clinical, biochemical and endoscopic variables. Patients with severe UC must be hospitalized. First line therapy is the use of intravenous corticoids which achieve clinical remission in most patients. However, 25% of patients will be refractory to corticoids, situation that should be evaluated at the third day of therapy. In patients without response, cytomegalovirus infection must be quickly ruled out to escalate to second line therapy with biological drugs or cyclosporine. Total colectomy must not be delayed if there is no response to second line therapy, if there is a contraindication for second line therapies or there are complications such as: megacolon, perforation or massive bleeding. An active management with quick escalation on therapy allows to decrease the prolonged exposure to corticoids, reduce colectomy rates and its perioperative complications.

Validation of the Simplified Criteria for the Diagnosis of Autoimmune Hepatitis in Chilean-Hispanic Patients.

INTRODUCTION AND AIM In 2008 the International autoimmune hepatitis (AIH) Group proposed the simplified diagnostic criteria for this disease. The original cohort study was performed in 11 international centers, but validation studies are scarce in Latin-America. The aim of this study is validate these criteria in Hispanic patients. MATERIAL AND METHODS A retrospective cohort of patients undergoing percutaneous liver biopsy and follow-up of at least 12 months was recruited from a Chilean University hospital. Patients with previous immunosuppressive therapy and liver transplant recipients were excluded. The diagnostic accuracy was analyzed using as gold standard the clinical course during long-term follow-up. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) and area under the ROC curve (AUROC) were calculated. RESULTS Four hundred eighty one patients were evaluated, 294 were included. 218 (74.15%) were female, mean age 48.5 (± 12.3) years, mean follow-up 34 (± 18) months. 66 patients had AIH or overlap syndrome (22.45%), 96 (32.65%) non-alcoholic steatohepatitis, 40 (13.61%) primary biliary cholangitis, 31 (10.54%) hepatitis C, 8 (2.72%) hepatitis B, 53 (18.02%) other etiologies. The AUROC for AIH simplified criteria was 0.976. Using a cutoff ≥ 6 and ≥ 7 points, the sensitivity was 86.4% and 54.6%; specificity, 98.7% and 99.6%; PPV, 95% and 97.3%; and NPV, 96.2% and 88.6%, respectively. CONCLUSION Simplified criteria for the diagnosis of AIH have a high accuracy in our Chilean-Hispanic cohort. The female gender is strongly associated to AIH and could help in difficult cases. Further studies with a prospective design are necessary to confirm these observations.INTRODUCTION AND AIM In 2008 the International autoimmune hepatitis (AIH) Group proposed the simplified diagnostic criteria for this disease. The original cohort study was performed in 11 international centers, but validation studies are scarce in Latin-America. The aim of this study is validate these criteria in Hispanic patients. MATERIAL AND METHODS A retrospective cohort of patients undergoing percutaneous liver biopsy and follow-up of at least 12 months was recruited from a Chilean University hospital. Patients with previous immunosuppressive therapy and liver transplant recipients were excluded. The diagnostic accuracy was analyzed using as gold standard the clinical course during long-term follow-up. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) and area under the ROC curve (AUROC) were calculated. RESULTS Four hundred eighty one patients were evaluated, 294 were included. 218 (74.15%) were female, mean age 48.5 (± 12.3) years, mean follow-up 34 (± 18) months. 66 patients had AIH or overlap syndrome (22.45%), 96 (32.65%) non-alcoholic steatohepatitis, 40 (13.61%) primary biliary cholangitis, 31 (10.54%) hepatitis C, 8 (2.72%) hepatitis B, 53 (18.02%) other etiologies. The AUROC for AIH simplified criteria was 0.976. Using a cutoff ≥ 6 and ≥ 7 points, the sensitivity was 86.4% and 54.6%; specificity, 98.7% and 99.6%; PPV, 95% and 97.3%; and NPV, 96.2% and 88.6%, respectively. CONCLUSION Simplified criteria for the diagnosis of AIH have a high accuracy in our Chilean-Hispanic cohort. The female gender is strongly associated to AIH and could help in difficult cases. Further studies with a prospective design are necessary to confirm these observations.

Atypical presentation of pseudomembranous colitis localized in adenomatous polyps

The most frequent cause of pseudomembranous colitis is Clostridium difficile (C. difficile) infection. This type of colitis is characterized by an endoscopic pattern of numerous small, yellowish or whitish plaques diffusely distributed, which typically compromises the rectum extending to proximal colon. Occasionally, the pseudomembranes compromise only the transverse or right colon, but their exclusive localization over polyps has not been reported. In this case report we have described a patient with symptoms compatible with C. difficile infection and positive for C. difficile toxigenic culture. Colonoscopy examination showed two small polyps with a whitish surface, and histopathological analysis confirmed them to be pseudomembranes over tubular adenomas. The rest of the colonic mucosa was normal and no other cause was demonstrated. We suggest that this particular distribution might be due to a higher affinity for dysplastic cells such as adenomatous polyps of colon by C. difficile and/or its toxins.

Fragmento sérico de citoqueratina-18 como marcador no invasivo de esteatohepatitis no alcohólica en población chilena

Nonalcoholic steatohepatitis (NASH) is the most aggressive form of nonalcoholic fatty liver disease (NAFLD) and involves the risk of progression to more advanced stages of liver disease. Non-invasive methods are needed to identify patients with NASH. OBJECTIVE To evaluate the diagnostic performance of the determination of serum levels of cytokeratin-18 (CK-18) as a non-invasive marker of NASH in the Chilean population. METHODS Serum CK-18 levels were determined in a group of 41 patients with biopsy-proven NAFLD. NASH diagnosis was based on Brunts criteria (histological parameters and ballooning), and the NAFLD activity score (NAS) and the presence of fibrosis were determined. The correlation between the NAFLD activity score (NAS) and CK-18 was evaluated with Spearmans rank correlation coefficient. A ROC curve was produced to assess the diagnostic value of CK-18 for NASH. The NAFLD fibrosis score (NFS) (to predict fibrosis and NASH) was compared to CK-18 with simple linear regression. Data were expressed in median [25th-75th percentile] and evaluated with the Wilcoxon rank test. RESULTS The mean age of the study group (23% male) was 50.4±11.1 years. 34.2% were diagnosed with NASH (NAS≥5). CK-18 levels were significantly higher in patients with NASH versus those without NASH (183.6 IU/l [97.4 to 734.4] vs. 117.2 IU/l [83.8 to 954.8], p= 0.016). CK-18 levels were a good predictor of NASH on biopsy with an area under the curve (AUC) of 0.732 (95% CI, 0.572 to 0.897). A CK-18 cut-off of 130.5 IU/l had a sensitivity of 92.9%, specificity of 63%, positive predictive value of 56.5% and negative predictive value of 94.4%, and was able to correctly classify 73.2% of patients with NASH. NFS identified advanced liver fibrosis (AUC 0.739, 95% CI, 0.56-0.91), but was of limited value to identify NASH (AUC 0.413, 95% CI, 0.21-0.61). CONCLUSION CK-18 is a good non-invasive marker for NASH. Although NFS was found to be an accurate marker of advanced liver fibrosis, it was not of value to identify NASH. In patients with NAFLD, CK-18 and NFS could be useful in predicting NASH and liver fibrosis, respectively.