Infección por Clostridium difficile: descripción de las cepas NAP1/027 y de otros serotipos en un centro de alta complejidad de Cali, Colombia, 2012-2015 / Clostridium difficile infection: Description of NAP1/027 and non NAP1/027 strains in a high complexity center in Cali, Colombia, 2012-2015

Resumen Introducción. Clostridium difficile ocasiona infecciones hospitalarias que resultan en altas tasas de morbilidad y mortalidad. La cepa NAP1/027 se ha asociado con una mayor producción de toxinas y con una mayor gravedad, lo que aumenta la carga de la enfermedad. Objetivo. Describir la epidemiología de las infecciones asociadas con C. difficile y las características de la cepa NAP1/027. Materiales y métodos. Se hizo un estudio observacional basado en la revisión de las historias clínicas de los pacientes con muestras de heces positivas para C. difficile identificadas mediante la prueba Xpert™ entre el 2012 y el 2015 en un hospital de alta complejidad. La gravedad de la enfermedad se evaluó con el índice ATLAS. Resultados. Se incluyeron 42 casos de pacientes infectados, 9 de los cuales fueron positivos para la cepa NAP1/027. El uso de antibióticos antes de la infección durante más de siete días fue más frecuente en los casos de pacientes con muestras negativas para NAP1/027. En la mitad de los pacientes, la duración de la diarrea fue mayor de cinco días y no hubo diferencias según el tipo de cepa (p>0,05). Los casos de pacientes positivos para la cepa NAP1/027 se caracterizaron por presentar deposiciones fétidas y sanguinolentas. La gravedad de la infección fue similar entre los grupos. Conclusión. Se comprobó la circulación de la cepa NAP1/027, pero su presencia no supuso diferencias clínicas significativas con respecto a otras cepas, lo cual podría deberse al limitado número de pacientes en este estudio. Sin embargo, su presencia debe alertar a los médicos y a las instituciones de salud, dada su frecuente asociación con la gravedad de la infección y la mortalidad.

Abstract Introduction: Clostridium difficile causes nosocomial infections leading to high morbidity and mortality. The NAP1/027 strain is associated with a higher toxin production and disease severity, which increases the load of the disease. Objective: To describe the epidemiology of the infections associated with C. difficile and the characteristics related to the NAP1/027 strain. Materials and methods: This was an observational study based on the revision of clinical registries of patients with fecal samples that were positive for C. difficile identified by the Xpert test™ between 2012 and 2015 in a high complexity institution. The severity of the disease was evaluated by means of the ATLAS score. Results: We included 42 infected cases, 9 of which were positive for the NAP1/027strain. The use of antibiotics previous to the infection for more than seven days was more frequent in patients with negative results for NAP1/027. The duration of diarrhea in half of the patients was longer than five days and there were no differences according to the type of strain (p>0.05). Positive cases for the NAP1/027 strain were characterized by presenting fetid and bloody stools. The severity of the infection was similar between the groups. Conclusions: In Colombia, the NAP1/027 strain circulates without significant clinical differences, which could be due to the limited number of patients. Nevertheless, the existence of NAP1/027 should alert physicians and health institutions because of its high association with severity and mortality.

Características de la infección por Clostridium difficile en una institución de alta complejidad y reporte de la circulación en Colombia de la cepa hipervirulenta NAP1/027 / Characteristics of Clostridium difficile infection in a high complexity hospital and report of the circulation of the NAP1/027 hypervirulent strain in Colombia

Resumen Introducción. Clostridium difficile es el principal responsable de la diarrea asociada al uso de antibióticos. En Colombia y en Latinoamérica, el conocimiento sobre el comportamiento epidemiológico de la infección por C. difficile todavía es limitado. Objetivo. Describir las características de una serie de pacientes con infección por C.difficile . Materiales y métodos. Se hizo un estudio descriptivo de una serie de casos de pacientes con infección por C. difficile atendidos en la Fundación Clínica Shaio, entre enero de 2012 y noviembre de 2015. Resultados. Se estudiaron 36 pacientes con una edad promedio de 65 años. Se determinaron los siguientes factores relacionados con la infección por C. difficile: uso previo de antimicrobianos (94,4 %), hospitalización en los últimos tres meses (66,7 %) y uso de inhibidores de la bomba de protones (50 %). Las comorbilidades más comunes fueron la enfermedad renal crónica (41,7 %) y la diabetes mellitus (30,6 %). Los síntomas más frecuentes fueron más de tres deposiciones diarreicas (97,1 %) y dolor abdominal (42,9 %). En cuanto a la gravedad de los casos, 44,4 % se clasificó como leve a moderado, 38,9 % como grave, y 11,1 % como complicado o grave. El método de diagnóstico más utilizado (63,8% de los pacientes) fue la identificación de la toxina mediante reacción en cadena de la polimerasa (PCR). La mortalidad global durante la hospitalización fue de 8 %. Se identificaron cuatro cepas del serotipo NAP1/027 y nueve muestras fueron positivas para la toxina binaria. Conclusión. La infección por C. difficile debe sospecharse en pacientes con deposiciones diarreicas y factores asociados tradicionalmente a esta enfermedad. Se reportó la circulación de cepas hipervirulentas del serotipo NAP1/027 en Colombia, lo cual debe enfrentarse con la vigilancia epidemiológica y el diagnóstico temprano.

Abstract Introduction: Clostridium difficile is the main pathogen related to healthcare-associated diarrhea and it is the cause of 20 to 30% of diarrhea cases caused by antibiotics. In Colombia and Latin America, the knowledge about the epidemiological behavior of this infection is limited. Objective: To describe the characteristics of a series of patients with C. difficile infection. Materials and methods: We performed a descriptive case series study of patients with C. difficile infection hospitalized in the Fundación Clínica Shaio from January, 2012, to November, 2015. Results: We analyzed 36 patients. The average age was 65 years. The risk factors associated with the infection were: previous use of antibiotics (94.4%), prior hospitalization in the last three months (66.7%) and use of proton pump inhibitors (50%). The most common comorbidities were chronic kidney disease (41.7%) and diabetes mellitus (30.6%). The most frequent symptoms were more than three loose stools per day (97.1%) and abdominal pain (42.9%). According to the severity of the disease, 44.4% of cases were classified as mild to moderate, 38.9% as severe, and 11.1% as complicated or severe. The detection of the toxin by PCR (GeneXpert) was the most common diagnostic procedure (63.8%). Global mortality during hospitalization was 8%. We identified four strains with serotype NAP1/027 and nine samples positive for binary toxin. Conclusion: Clostridium difficile infection should be suspected in patients with diarrhea and traditional risk factors associated with this disease. We report the circulation of the hypervirulent strain serotype NAP1/027 in Colombia, which should be countered with epidemiological surveillance and a prompt diagnosis.

Clostridium difficile outbreak caused by NAP1/BI/027 strain and non-027 strains in a Mexican hospital

Abstract Background Clostridium difficile infections caused by the NAP1/B1/027 strain are more severe, difficult to treat, and frequently associated with relapses. Methods A case–control study was designed to examine a C. difficileinfection (CDI) outbreak over a 12-month period in a Mexican hospital. The diagnosis of toxigenic CDI was confirmed by real-time polymerase chain reaction, PCR (Cepheid Xpert C. difficile/Epi). Results During the study period, 288 adult patients were evaluated and 79 (27.4%) patients had confirmed CDI (PCR positive). C. difficilestrain NAP1/B1/027 was identified in 31 (39%) of the patients with confirmed CDI (240 controls were included). Significant risk factors for CDI included any underlying disease (p < 0.001), prior hospitalization (p < 0.001), and antibiotic (p < 0.050) or steroid (p < 0.001) use. Laboratory abnormalities included leukocytosis (p < 0.001) and low serum albumin levels (p < 0.002). Attributable mortality was 5%. Relapses occurred in 10% of patients. Risk factors for C. difficileNAP1/B1/027 strain infections included prior use of quinolones (p < 0.03). Risk factors for CDI caused by non-027 strains included chronic cardiac disease (p < 0.05), chronic renal disease (p < 0.009), and elevated serum creatinine levels (p < 0.003). Deaths and relapses were most frequent in the 027 group (10% and 19%, respectively). Conclusions C. difficile NAP1/BI/027 strain and non-027 strains are established pathogens in our hospital. Accordingly, surveillance ofC. difficile infections is now part of our nosocomial prevention program.

Investigation of Toxin Gene Diversity, Molecular Epidemiology, and Antimicrobial Resistance of Clostridium difficile Isolated from 12 Hospitals in South Korea / 대한진단검사의학회지

BACKGROUND: Clostridium difficile is a major cause of antibiotic-associated diarrhea. The objective of this study was to characterize clinical isolates of C. difficile obtained from various regions in Korea with regard to their toxin status, molecular type, and antimicrobial susceptibility. METHODS: We analyzed a total of 408 C. difficile isolates obtained between 2006 and 2008 from 408 patients with diarrhea in 12 South Korean teaching hospitals. C. difficile toxin genes tcdA, tcdB, cdtA, and cdtB were detected by PCR. Molecular genotyping was performed by PCR ribotyping. Antimicrobial susceptibilities of the 120 C. difficile isolates were assessed by agar dilution methods. RESULTS: Among 337 toxigenic isolates, 105 were toxin A-negative and toxin B-positive (A-B+) and 29 were binary toxin-producing strains. PCR ribotyping showed 50 different ribotype patterns. The 5 most frequently occurring ribotypes comprised 62.0% of all identified ribotypes. No isolate was susceptible to cefoxitin, and all except 1 were susceptible to piperacillin and piperacillin-tazobactam. The resistance rates of isolates to imipenem, cefotetan, moxifloxacin, ampicillin, and clindamycin were 25%, 34%, 42%, 51%, and 60%, respectively. The isolates showed no resistance to metronidazole or vancomycin. CONCLUSIONS: This is the first nationwide study on the toxin status, including PCR ribotyping and antimicrobial resistance, of C. difficile isolates in Korea. The prevalence of A-B+ strains was 25.7%, much higher than that reported from other countries. Binary toxin-producing strains accounted for 7.1% of all strains, which was not rare in Korea. The most prevalent ribotype was ribotype 017, and all A-B+ strains showed this pattern. We did not isolate strains with decreased susceptibility to metronidazole or vancomycin.

The First Case of Antibiotic-associated Colitis by Clostridium difficile PCR Ribotype 027 in Korea

Clostridium difficile (C. difficile) is a common causative agent of pseudomembranous colitis (PMC). C. difficile-associated diarrhea (CDAD) ranges from mild diarrhea to life threatening PMC. Recently, a highly virulent strain of C. difficile polymerase chain reaction ribotype 027 was found in North America, Europe, and Japan. A 52-yr-old woman with anti-tuberculosis medication and neurogenic bladder due to traffic accident experienced five episodes of C. difficile PMC after taking antibiotics for pneumonia along with septic shock and acute renal failure. She was readmitted to the intensive care unit and treated with oral vancomycin with refractory of oral metronidazole, inotropics and probiotics for over 60 days. C. difficile isolated both at the first and the last admission was identified as C. difficile ribotype 027 by ribotyping, toxinotyping, and tcdC gene sequencing, which turned out the same pathogen as the epidemic hypervirulent B1/NAP1 strain. This is the first case of C. difficile PCR ribotype 027 in Korea. After discharge, she was maintained on probiotics and rifaximin for 3 weeks. She had no relapse for 6 months.