Análisis clínico y microbiológico de la sepsis grave y el choque séptico por Escherichia coli en Medellín, Colombia / Severe sepsis and septic shock by Escherichia coli, clinical and microbiological analysis in Medellin, Colombia

Resumen Introducción: Escherichia coli es causa frecuente de un amplio espectro de infecciones, desde una infeccion urinaria no complicada hasta la sepsis grave y el choque septico, asociadas con desenlaces de alto impacto como ingreso a UCI y mortalidad. Objetivos: Determinar las diferencias en mortalidad. ingreso a UCI/UCE, presencia de cepas BLEE y tratamiento antimicrobiano en pacientes con sepsis grave y choque séptico por E. coli, con o sin bacteriemia, asi como su variabilidad dependiendo del foco infeccioso. Material y Métodos: Análisis secundario de estudio de cohorte prospective multicéntrico. Resultados: De 458 pacientes que tenian infeccion por E. coli, 123 tenian aislamiento solo en hemocultivo, 222 solo en urocultivo y 113 en ambas muestras. El aislamiento solo en hemocultivo se asocio mayor frecuencia de ingreso a UCI (n = 63; 5,2%). mayor necesidad de ventilacion mecánica (n = 19; 15,5%), mayor mortalidad y estancia hospitalaria (n = 22; 18%; mediana de 12 dias, RIQ= 7-17, respectivamente), pero con menor presencia de cepas productoras de BLEE en comparacion con urocultivos y hemocultivo, urocultivo (n = 20; 17,7% y n = 46; 20,7%, respectivamente). Recibieron tratamiento antimicrobiano en las primeras 24 h 424 pacientes (92,6%), con mas frecuencia piperacilina/ tazobactam (n = 256,60,3%). La proporcion de pacientes tratados empiricamente con carbapenemicos vs no carbapenemicos fue similar en los tres grupos. Discusión: El foco infeccioso. sumado a factores de nesgo para cepas productoras de BLEE, son herramientas utiles para definir pronostico y tratamiento en esta población, debido a la variabilidad clínica y microbiologica en los distintos aislados. Conclusión: Los pacientes con aislamiento de E. coli solo en hemocultivo presentan con mayor frecuencia desenlaces desfavorables en comparación con los pacientes con E. coli en urocultivo, con o sin bacteriemia. Llama la atencion en nuestro medio la menor cantidad de cepas productoras de BLEE en los pacientes con solo hemocultivo positivo.

Background: Escherichia coli is a common cause of a broad spectrum of infections, from non-complicated urinary tract infection, to severe sepsis and septic shock, that are associated to high impact outcomes, such as ICU admission and mortality. Aims: To establish differences in mortality, ICU admission, ESBL positive strains and antibiotic treatment, between patients with E. coli related severe sepsis and septic shock, with or without bacteremia and its variability based on the source of infection. Method: Secondary data analysis of a multicentric prospective cohort study. Results: From 458 patients with E. coli isolation, 123 had E. coli exclusively in blood culture, 222 solely in urine culture, and 113 in both samples. Escherichia coli isolation exclusively in blood culture was associated with higher frequency of ICU admission (n = 63; 51.2%), higher rate of mechanical ventilation requirement (n = 19; 15.5%), higher mortality and longer hospital stay (n = 22; 18%; median of 12 days, IQR= 7 - 17, respectively); but with a lower occurrence of ESBL strains, compared to patients with positive urine culture and positive blood/urine cultures (n = 20; 17.7% and n = 46; 20.7%, respectively). 424 patients (92.6%) received antibiotic treatment in the first 24 hours. The most commonly prescribed was piperacilin/tazobactam (n = 256;60.3%). The proportion of patients empirically treated with carbapenems vs non-carbapenems was similar in the three groups. Discussion: The source of infection, associated with ESBL strains risk factors, are useful tools to define prognosis and treatment in this population, because of their clinical and microbiological variability. Conclusion: Patients with E. coli isolation exclusively in the blood culture had higher frequency of non-favorable outcomes in comparison to patients with E. coli in urine culture with or without bacteremia. Additionally, in our population patients with E. coli solely in blood culture have lower prevalence of ESBL positive strains.

Mortalidad por bacteriemia causada por Escherichia coli y Klebsiella spp. productoras de beta lactamasas de espectro extendido: cohorte retrospectiva en un hospital de Lima, Perú / Mortality caused by bacteremia Escherichia coli and Klebsiella spp. extended-spectrum beta-lactamase- producers: a retrospective cohort from a hospital in Lima, Peru

Objetivos. Evaluar los factores asociados a la mortalidad causada por bacteriemias por Escherichia coli y Klebsiella spp. productoras de beta lactamasas de espectro extendido (BLEE). Materiales y Métodos. Se realizó un estudio de cohortes retrospectivo, que incluyó 85 pacientes mayores de 16 años con diagnóstico de bacteriemia por Escherichia coli o Klebsiella spp. hospitalizados entre 2006 y 2008 en el Hospital Nacional Cayetano Heredia. Las cohortes se clasificaron de acuerdo a la producción de BLEE según los resultados de los hemocultivos. Se evaluaron los factores asociados a la mortalidad cruda y atribuible empleando regresión de Poisson en un modelo multivariado, con lo que se obtuvo riesgos relativos ajustados (RRa). Además, se construyeron curvas de mortalidad. Resultados. Se encontró que el 35,3% de las bacteriemias fueron debidas a cepas productoras de BLEE. El análisis de la mortalidad cruda mostró una mayor mortalidad en el grupo de cepas productoras de BLEE (63,3%). El RRa fue de 1,5 (IC95%: 1,02-2,3). En el caso de mortalidad atribuible, la proporción también fue mayor (63,3%), el RRa fue de 1,9 (IC95%: 1,2-2,9). El uso de catéter venoso central fue otro factor asociado tanto a la mortalidad cruda (RRa= 2,4; IC95%: 1,2- 4,8) como a la mortalidad atribuible (RRa= 3,8; IC95%: 1,6-8,8). Conclusiones. La producción de BLEE es un factor de riesgo independiente para mortalidad por bacteriemia causada por E. coli y Klebsiella spp. Su presencia debe evaluarse tras la sospecha diagnóstica y la elaboración de la terapéutica inicial, lo que podría disminuir la mortalidad por esta causa.

Objectives. To evaluate the factors associated to mortality caused by bacteremia due to Escherichia coli and Klebsiella spp. producers of extended-spectrum beta-lactamase (ESBL). Materials and methods. We performed a retrospective cohort study, including 85 patients older than 16 and diagnosed with bacteremia by Escherichia coli or Klebsiella spp., hospitalized between 2006 and 2008 in Cayetano Heredia National Hospital. Cohorts were classified according to the ESBL production following blood culture results. Factors associated to gross and attributable mortality were evaluated using the Poisson regression in a multivariate model, through which adjusted relative risks (ARRs) were obtained. Mortality curves were also built. Results. 35.3% of bacteremia cases were caused by ESBL-producing strains. The analysis of gross mortality showed a higher mortality rate in the group with ESBL producing strains (63.3%), ARR being 1.5 (CI 95%: 1.02-2.3). In the case of the attributable mortality, the proportion was also higher (63.3%), ARR being 1.9 (CI 95%: 1.2-2.9). The use of a central venous catheter was another factor associated to both gross mortality (ARR= 2.4; CI 95%: 1.2-4.8) and attributable mortality (ARR= 3.8; CI 95%: 1.6-8.8). Conclusions. The production of ESBL is an independent risk factor for bacteremia mortality caused by E. coli and Klebsiella spp. Its presence should be evaluated following diagnosis consideration and initial therapy elaboration, which could in turn decrease the mortality by this cause.

Enterohaemorrhagic E. coli outbreak in Germany

As of 10 June 2011, the German health authorities have reported 2374 cases of Entero-haemorrhagic Escherichia Coli [EHEC] and 773 cases of Haemolytic Uraemic Syndrome [HUS]. There were 22 and 12 related deaths respectively. The outbreak has since spread to 13 other countries in Europe with a total of 66 EHEC cases and 36 HUS cases with one death reported. Three HUS cases linked to this outbreak were reported from the United States. The source of infection for this outbreak is now believed to originate from contaminated bean sprout from a farm in Germany. The outbreak started in early May

Risk factors for and mortality of extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae and Escherichia coli nosocomial bloodstream infections / Fatores de risco e mortalidade de infecções da corrente sanguínea por Klebsiella pneumoniae and Escherichia coli produtores de beta-lactamase de espectro estendido

A case-control study, involving patients with positive blood cultures for Klebsiella pneumoniae (KP) or Escherichia coli (EC) EC and controls with positive blood cultures for non-ESBL-KP or EC, was performed to assess risk factors for extended-spectrum-β-lactamase (ESBL) production from nosocomial bloodstream infections (BSIs). Mortality among patients with BSIs was also assessed. The study included 145 patients (81, 59.5 percent with K. pneumoniae and 64, 44.1 percent with E. coli BSI); 51 (35.2 percent) isolates were ESBL producers and 94 (64.8 percent) nonproducers. Forty-five (55.6 percent) K. pneumoniae isolates were ESBL producers, while only six (9.4 percent) E. coli isolates produced the enzyme. Multivariate analysis showed that recent exposure to piperacillin-tazobactam (adjusted Odds Ratio [aOR] 6.2; 95 percentCI 1.1-34.7) was a risk factor for ESBL BSI. K. pneumoniae was significantly more likely to be an ESBL-producing isolate than E. coli (aOR 6.7; 95 percentCI 2.3-20.2). No cephalosporin class was independently associated with ESBLs BSI; however, in a secondary model considering all oxymino-cephalosporins as a single variable, a significant association was demonstrated (aOR 3.7; 95 percentCI 1.3-10.8). Overall 60-day mortality was significantly higher among ESBL-producing organisms. The finding that piperacillin-tazobactam use is a risk factor for ESBL-production in KP or EC BSIs requires attention, since this drug can be recommended to limit the use of third-generation cephalosporins.

Estudo de caso-controle, onde os casos foram pacientes com hemocultura positiva para Klebsiella pneumoniae (KP) ou Escherichia coli (EC) produtores de beta lactamase de espectro estendido (ESBL) e os controles foram pacientes com hemoculturas positivas para EC ou KP não produtores de ESBL foi realizado para avaliar os fatores de risco para produção destas enzimas em infecções da corrente sanguínea (ICS). Mortalidade dos pacientes com ICS também foi avaliada. Foram incluídos 145 pacientes (81, 59,5 por cento tinham Klebsiella pneumoniae e 64, 44,1 por cento tinham Escherichia coli); 51 (35,2 por cento) isolados eram produtores de ESBL e 94 (64,8 por cento) eram não produtores. Quarenta e cinco (55,6 por cento) isolados de K. pneumoniae e somente seis (9,4 por cento) isolados de E. coli eram produtores de ESBL. Análise multivariada mostrou que exposição recente a piperacilina-tazobactam (OR ajustado [aOddsRatio] 6,2; 95 por cento Intervalo de Confiança [IC] 1,1-34,7) foi fator de risco para infecção da corrente sanguínea por ESBL. Foi significativamente maior a chance de K. pneumoniae ser um isolado produtor de ESBL do que E. coli o ser (aOR 6,7; 95 por cento CI 2,3-20,2). Nenhuma classe de cefalosporina foi independentemente associada com ESBL-ICS. No entanto, em um modelo secundário considerando todas as oximino-cefalosporinas como variável única, foi demonstrada associação significativa (aOR 3,7; 95 por cento IC 1,3-10,8). Mortalidade total em 60 dias foi significativamente maior entre isolados produtores de ESBL. O achado de piperacilina-tazobactam como fator de risco para produção de ESBL em ICS por KP ou EC requer atenção, uma vez que esta droga tem sido eventualmente recomendada para poupar o uso de cefalosporinas de terceira geração.

Inadequate timing between corticosteroid and antibiotics applications increases mortality due to sepsis

This study tested the hypothesis that the use of corticosteroids prior to antibiotics can lower the mortality rate in severe infections by S. aureus or Gram-negative bacilli, using an animal model. This study was a prospective and controlled study, placed in a university laboratory. Seven hundred and sixty mice distributed into three groups (Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae infected). The interventions in each group were: I) infection control (intra-peritoneal); II) treatment solely with antibiotics (teicoplanin or amikacin); III) antibiotics administered prior to the corticosteroid (methylprednisolone); IV) antibiotics administered after the corticosteroid. Mortality in the E. coli group, subgroup I: 100 percent; subgroup II: 55 percent (p<0.001); subgroup III: 62.5 percent (p=0.2488, compared to subgroup II); subgroup IV: 20 percent (p<0.01 compared to subgroups II and III). Mortality in the K. pneumoniae group: subgroup I: 100 percent; subgroup II: 72.5 percent (p<0.01); subgroup III: 80 percent (p=0.215 compared to subgroup II); subgroup IV: 45 percent (p<0.01 compared to subgroups II and III). Mortality in the S. aureus group: subgroup I: 82.5 percent; II: 42.5 percent (p<0.001); subgroup III: 77.5 percent (p=0.2877 compared to subgroup I); subgroup IV: 32.5 percent (p=0.1792 compared to subgroup II). The use of corticosteroids prior to antibiotics lowered the mortality rate caused by Gram-negative bacteria and did not affect the mortality caused by S. aureus. When used after starting treatment with antibiotics, the corticosteroid was not superior to the use of antibiotics alone in the case of the Gram-negative bacteria, and was not significantly different from non-treatment of the infection, in the case of S. aureus.

Antagonic effect of the inhibition of inducible nitric oxide on the mortality of mice acutely infected with Escherichia coli and Bacteroides fragilis

Sepsis, the leading cause of death in intensive care units, is associated with overproduction of nitric oxide (NO) due to inducible NO synthase (iNOS), responsible for some of the pathologic changes. Aminoguanidine (AG) is a selective iNOS inhibitor with reported inconsistent actions in sepsis. To investigate the influence of iNOS, we studied models of acute bacterial sepsis using acute challenges with aerobic (Escherichia coli) and anaerobic (Bacteroides fragilis) bacteria in the presence of AG. Six-week-old, 23 g, male and female BALB/c and C57Bl/6j mice, in equal proportions, were inoculated (ip) with bacteria in groups of 4 animals for each dose and each experiment in the absence or presence of AG (50 mg/kg, ip, starting 24 h before challenge and daily until day 6) and serum nitrate was measured by chemiluminescence. Both types of bacteria were lethal to mice, with an LD50 of 6 nephelometric units (U) for E. coli and 8 U for B. fragilis. Nitrate production peaked on the second day after E. coli inoculation with 8 and 6 U (P < 0.05), but was absent after non-lethal lower doses. After challenge with B. fragilis this early peak occurred at all tested doses after 24 h, including non-lethal ones (P < 0.05). AG-treated mice challenged with E. coli presented higher survival (P < 0.05) and increased LD50. AG-treated mice challenged with B. fragilis had lower LD50 and higher mortality. Control AG-treated animals presented no toxic effects. The opposite effect of iNOS blockade by AG in these models could be explained by restriction of oxygen for immune cells or an efficient action of NO in anaerobic localized infections. The antagonic role of NO production observed in our bacterial models could explain the reported discrepancy of NO action in sepsis.

Características clínicas e epidemiológicas da diarréia aguda por Escherichia Coli enteropatogênica clássica / Clinical and epidemiological characteristics of acute diarrhea by classical enteropathogenic Escherichia coli

Diarréia aguda é tradicionalmente considerada uma síndrome de evoluçao autolimitada na grande maioria dos casos, mas, em algumas cireunstâncias, a influência do agente etiológico, a idade e o estado nutricional do paciente constituem-se em fatores que podem acarretar persistência da diarréia. OBJETIVOS. Neste trabalho, os autores descrevem as características clínicas e epidemiológicas de um grupo de 84 lactentes menores de 2 anos com diarréia aguda provocada por sorogrupos de Escherichia coli enteropatogênica (EPEC). PACIENTES E MÉTODO. Durante período de dois anos, foram estudados 200 lactentes menores de 2 anos de idade, média 8,2 meses, com diarréia aguda de duraçao inferior a cinco días. Grupo controle composto por 40 lactentes sadios, pareados pela idade, foi formado. 0 estado nutricional das crianças foi avaliado e a ocorrência de intolerancia alimentar foi detectada. Os pacientes foram acompanhados clinicamente durante quatro semanas após a alta hospitalar. Amostras de fezes foram colhidas para pesquisa dos principais agentes enteropatogênicos bacterianos, virais e protozoários. RESULTADOS. EPEC foi isolada nas fezes de 84 (42,0 por cento) dos pacientes, dos quais em 55 (27,5 por cento) como agente enteropatogênico único, enquanto que nos 29 (14,5 por cento) restantes associada com outro agente. EPEC foi isolada em 9 (22,5 por cento) crianças pertencentes ao grupo controle (p<0,05). Intolerância alimentar foi a principal complicaçao digestiva e, também, o fator mais importante de perpetuaçao da diarréia. A duraçao média da doença foi de 11,2 dias, variando de 2 a 40 adias. Em 53 (71,6 por cento) lactentes a doença durou menosde 14 dias, enquanto que nos 21 (28 por cento) restantes teve duraçao superior a 14 dias e, em todos estes casos, houve intolerância alimentar. CONCLUSAO. Infecçao intestinal por sorogrupos de EPEC, em particular 0111 e 0119, afeta lactentes preferencialmente menores de 1 ano de idade pertencentes a famílias de baixa renda que sofreram desmame precoce e que necessitam, freqüentemente, internaçao hospitalar devido às grandes perdas fluidas e eletrolíticas fecais.