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.

Community-associated methicillin-resistant Staphylococcus aureus in non-outbreak skin infections

The aim of this study was to determine the prevalence of Staphylococcus aureus and risk factors for the acquisition of MRSA (Methicillin Resistant Staphylococcus aureus) as the main cause of skin and soft tissue infections. S. aureus were characterized for the presence of PVL, TSST-1 and mecA genes. SCCmec typing was carried out in mecA positive strains and PFGE was performed only in these strains. During the study period, 127 outpatients attending a dermatology clinical the Botucatu Medical School, a regional tertiary hospital in Botucatu, Sao Paulo, Brazil, were diagnosed with active skin infections. A total 66 (56.9%) S. aureus strains were isolated. The methicillin resistance gene mecA was detected in seven (10.6%) S. aureus strains. The SCCmec types detected in the seven mecA-positive S. aureus strains were type Ia in one, type II in three, and type IV in three. The PVL gene was detected in 10 (15.1%) in sensitive strains. Pulsed field gel electrophoresis revealed non-clonal diversity among the isolates. The risk factors associated with MRSA acquisition in this study were previous ciprofloxacin use and working in a healthcare environment. The risk factors indicate plausible routes of CA-MRSA transmission among the subjects studied.

Factors associated with Clostridium difficile diarrhea in a hospital in Beijing, China

Clostridium difficile is the most common cause of hospital-acquired diarrhea in patients treated with antibiotics, chemotherapeutic agents, and other drugs that alter the normal equilibrium of the intestinal flora. A better understanding of the risk factors for C. difficile-associated disease (CDAD) could be used to reduce the incidence of CDAD and the costs associated with its treatment. The aim of this study was to identify the risk factors for CDAD in a cohort of Chinese patients in a Beijing hospital. Medical charts of a total of 130 inpatients (62 males and 68 females) with hospital-acquired diarrhea (45 with CDAD; 85 without CDAD) were retrospectively reviewed. C. difficile toxins A and B were detected in fecal samples using enzyme-linked fluorescence assays. The drugs used by patients with and without CDAD before the onset of diarrhea were compared. Factors that differed significantly between the two groups by univariate analysis were analyzed by multivariate analysis using a logistic regression model. Multivariate analysis showed that cephalosporin treatment was associated with a significantly higher risk of CDAD in hospitalized patients, while treatment with glycopeptides was significantly associated with a reduction in CDAD (P<0.001 for cephalosporin; P=0.013 for glycopeptides). Our data confirmed previous findings that empirical treatment with cephalosporins is positively associated with CDAD compared to individuals using other CDAD-related drugs. Additionally, we showed that treatment with glycopeptides was negatively associated with CDAD, compared to individuals using other CDAD-related drugs.

Pseudo-outbreak of Clostridium difficile associated diarrhea (CDAD) in a tertiary-care hospital / Pseudo-surto de diarréia associada a Clostridium difficile (DACD) em hospital terciário

The objective of this study was to describe a pseudo-outbreak of C. difficile in a hospital, following a change in the method used to detect the toxin. In February 2002, there were two cases of CDAD and in March 7 occurred, coinciding with a change of the test (from detection of toxin A to toxin A/B). An outbreak was suspected. Active surveillance and education of staff were started. A CDAD case was defined as a patient with acute onset of diarrhea (³ three episodes of liquid stools) and a positive stool test. They were classified as hospital or community-acquired. Stool samples were also collected for C. difficile culture and isolates were typed using AP-PCR. From March 2002 through December 2003 there were 138 cases of CDAD: 70 percent were hospital-acquired and among the 30 percent with CDAD present on admission, most (81 percent) came directly from the community (50 percent had no history of hospitalization). Fifty-two percent of hospital-acquired CDAD and 94 percent of cases on admission had already used antibiotics. The incidence of CDAD in hospitalized patients during surveillance was 3.3 per 1000 patient-admissions. The incidence of CDAD present on admission was 6.1/1000 patients. Sixteen isolates were typed and presented 13 different profiles. In conclusion, the CDAD increase in our study occurred due to change in diagnostic methods and not due to an outbreak, as suspected initially. The incidence in hospitalized patients was much lower than in reported outbreaks. There were 13 molecular types suggesting that an outbreak did not occur. CDAD was largely community-acquired.

O objetivo deste estudo foi descrever um pseudo-surto de C. difficile em um hospital após a troca do método de detecção de toxina. Em fevereiro de 2002 houve dois casos de DACD e em março ocorreram sete casos, que coincidiram com a mudança de teste (que detectava apenas toxina A e passou a detectar toxinas A e B). Foi suspeitado que houvesse um surto e vigilância ativa e reforço educacional para os profissionais de saúde foi implantado. Um caso de DACD foi definido como um paciente com início abrupto de diarréia (> 3 episódios de fezes líquidas) e um teste positivo. Os casos foram classificados como de aquisição comunitária ou hospitalar. Foram colhidas fezes para cultura para C. difficile e os isolados foram tipados por AP-PCR. De março de 2002 a dezembro de 2003 houve 138 casos de DACD: 70 por cento foram hospitalares e, entre os 30 por cento de casos comunitários, a maioria (81 por cento) foi de pacientes provenientes diretamente da comunidade (50 por cento não tinham histórico de internação). Cinquenta e dois por cento dos casos de DCAD hospitalar e 94 por cento de casos na admissão haviam utilizado antimicrobianos. A incidência de DCAD em pacientes internados foi de 3,3/100 pacientes e na admissão foi 6,1/1000 pacientes. Dezesseis isolados foram tipados e apresentaram 13 perfis diferentes. Em conclusão, o aumento de DACD no nosso estudo ocorreu por uma mudança de método diagnóstico e não devido a um surto como foi suspeitado inicialmente. A incidência em pacientes internados foi muito inferior ao que já foi relatado em surtos. Houve 13 perfis moleculares sugerindo que não ocorreu um surto. DACD foi, em grande parte, de aquisição comunitária.

Nosocomial diarrhea in the intensive care unit

We made an epidemiological case-control study to examine risk factors for the development of diarrhea in the intensive care unit (ICU) of a public hospital in Santo André, SP, from January to October 2002. Forty-nine patients with diarrhea (cases) and 49 patients without diarrhea (controls), matched for age and gender, were included in the study. A stool culture and enzyme immunoassays for Clostridium difficile toxins A and B were performed on fecal specimens from diarrhea patients. Fourteen of them presented positive cultures for Pseudomonas aeruginosa and 22 patients presented positive ELISA for Clostridium diffícile. Nosocomial diarrhea was associated with several factors, including use of antibiotics (P=0.001), use of ceftriaxone (P=0.001), presence of infection (P=0.010) and length of hospital stay (P=0.0001).

Diarrea asociada a Clostridium difficile: frecuencia de detección en un centro médico de Buenos Aires, Argentina / Clostridium difficile diarrhea: frequency of detection in a medical center in Buenos Aires, Argentina

Clostridium difficile has been recognized as the most important enteric pathogen of nosocomial antibiotic-associated diarrhea (CDAD) in adults from industrialized countries. The importance of C. difficile as a cause of diarrhea in ambulatory patients appears underestimated or under-recognized. Since the 1980's, outbreaks of CDAD have been increasingly reported, but there are few data available in Argentina. We developed a retrospective study to provide some information about CDAD in our country. From July 1998 to November 1999, a total of 245 fecal specimens from hospitalized and some ambulatory patients were tested in order to confirm the diagnosis of CDAD. C. difficile cytotoxin (toxin B) was identified by detecting its cytopathic effect on monolayers of McCoy culture cells. For culture and isolation of C. difficile, stool samples were prepared by ethanol shock prior to plating onto a selective medium which contained blood, cefoxitin and fructose. Of the 245 samples, 14 (5.8) were identified as positive by the cell cytotoxicity assay. Using the criteria of isolation of cytotoxigenic C. difficile positivity increased to 6.5 (16 samples). Thirteen of the positive results were from hospitalized patients (81.3) and 3 (18.7) from outpatients. The mean age of inpatients was 72.9 years (ranging from 47 to 88). All patients had received 2 or more antimicrobial agents (most of them beta-lactams) 2 months before the appearance of diarrhea. There was one patient who had received only chemotherapy. The prevalence of CDAD in this study was less than in others previously reported. This difference may be due to the fact that not all general practitioners include testing for C. difficile when the patient with diarrhea had previously received antibiotics. More educational programs should be directed to all physicians, concerning the role of C. difficile as an important enteric pathogen in patients who have undergone treatment with antimicrobial or chemotherapeutic agents.

Antibiotic susceptibility of Clostridium difficile isolates from adult patients at two Jamaican hospitals. Clinical and epidemiological implications

The susceptibility of 39 toxin producing Clostridium difficile isolates from stools of hospitalized patients was determined, by disc diffusion, to six antibiotics. All but one isolate (toxin A negative) produced toxin A and toxin B. A wide variation in susceptibility to clindamycin, tetracycline and chloramphenicol was noted. Erythromycin and cotrimoxazole showed a clear-cut discrimination in resistance and susceptibility, while all isolates were sensitive to vancomycin. Erythromycin sensitive isolates demonstrated a significant association with diarrhoea (60.9, 14/23, p < 0.001). These strains were predominantly found at the University Hospital of the West Indies (UHWI, 94.1, 16/17). Strains resistant to erythromycin and clindamycin together were commonly found at the National Chest Hospital (NCH, 68.2, 15/22). All erythromycin sensitive strains found at the NCH were from patients transferred to that hospital. These findings suggest that there is a common strain of C difficile (erythromycin resistant) at the NCH different from that found at the UHWI; the resistant pattern seen with isolates from the NCH was typical of toxigenic serogroup C strain and could be typed by the the disc diffusion method. Patients at the NCH who were colonized with either of the two strains of C difficile were likely to get diarrhoea, once there was suppression of the normal microflora by antibiotics and colonic overgrowth with C difficile.

Sindrome uremico hemolitico en niños de Mendoza, Argentina: asociacion con la infeccion por Escherichia coli productor de toxina Shiga / Hemolytic uremic syndrome in children of Mendoza, Argentina: association with Shiga toxin-producing Escherichia coli infection

Escherichia coli productor de toxina Shiga (STEC) ha sido asociado con la etiopatogenia del síndrome urémico hemolítico (SUH). El objetivo fue caracterizar los casos de SUH observados en Mendoza y determinar su asociación con la infección por STEC. Entre el 1º de Julio de 1994 y el 30 de Junio de 1996 ingresaron al Hospital Pediátrico "Dr. HJ Notti", 36 pacientes con diagnóstico de SUH. La edad promedio fue de 22.8 meses, con un 44 por ciento en el sexo femenino. La enfermedad se estableció después de un período prodrómico de 4.5 días, el 94.4 por ciento de los pacientes presentó diarrea siendo sanguinolenta en el 83.3 por ciento de los casos. El 69.4 por ciento recibió antibioticoterapia antes de su ingreso. Los casos se presentaron fundamentalmente en niños eutróficos (88.9 por ciento), de condición socioeconómica media-baja (91.7 por ciento) de origem urbano (72.2 por ciento), durante el verano y principios de otoño. En el período de estado los pacientes presentaron palidez (100 por ciento), edema (25 por ciento), anuria (38.9 por ciento), oliguria (41.7 por ciento), anemia hemolítica (97.2 por ciento), trombocitopenia (86.1 por ciento) y compromiso neurológico (41.7 por ciento). Veinticinco pacientes presentaron formas completas de SUH. El 50 por ciento de los pacientes fue dializado y el 88.9 por ciento requirió transfusión de sedimento globular. El promedio de días de internación fue de 15.1. El 91.7 por ciento de los pacientes recuperó la función renal, dos pacientes evolucionaron a insuficiencia renal crónica y uno falleció. Evidencias acumulativas de infección por STEC se encontraron en 19 (86.4 por ciento) de 22 pacientes, STEC del serotipo 0157:H7, biotipo C fue detectado en 8 casos (36.4 por ciento). Stx2 fue la citotoxina prevalente en STEC, en materia fecal (STMF) y anticuerpos a-Stx.