RESUMEN
Coagulase-negative staphylococci (CoNS) are the most frequent contaminating bacteria; therefore, we aimed to investigate an indicator of CoNS to predict the increase in blood culture contamination rate (ConR). We performed a retrospective study of selected patients, who underwent blood culture testing. Contamination was defined as the presence of either one of two or more sets of skin-resident bacteria, except for cases with a low likelihood of contamination based on clinical aspects. We calculated the monthly ConR [(total number of contaminated cases per month)/(total number of blood culture sets collected per month) × 100] and analysed the ConR prediction ability using the following four indicators: the number of CoNS-positive sets of blood cultures, cases with at least one CoNS-positive blood culture set, cases with only one CoNS-positive blood culture set, and cases of contamination by CoNS. Cases with CoNS-positive blood cultures correlated with ConR (r = 0.85). Although the area under the receiver operating characteristic curve for the number of cases with ConR ≥ 2.5 differed significantly from that of the number of cases contaminated by CoNS, the negative predictive value was high, reaching up to 95.5% (95% confidential interval 87.3-99.1). The number of CoNS-positive cases could help predict an increase in ConR ≥ 2.5.
Asunto(s)
Bacteriemia/diagnóstico , Cultivo de Sangre/clasificación , Coagulasa/metabolismo , Infecciones Estafilocócicas/diagnóstico , Staphylococcus/aislamiento & purificación , Bacteriemia/enzimología , Bacteriemia/microbiología , Bacteriemia/patología , Cultivo de Sangre/métodos , Infección Hospitalaria/microbiología , Humanos , Curva ROC , Estudios Retrospectivos , Infecciones Estafilocócicas/enzimología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/patología , Staphylococcus/patogenicidadRESUMEN
During human diamine oxidase (DAO) ELISA development we noticed that in serum DAO concentrations appear to be higher when compared to plasma. Neutrophils contain DAO in the specific granules and we hypothesized that DAO is released from neutrophils during serum coagulation. If activation of neutrophils can release DAO, its concentrations might be elevated in vivo after lipopolysaccharide (LPS) administration and in bacteremic patients. Using blood from healthy volunteers DAO concentrations were measured ex vivo in serum, citrate, EDTA and heparin plasma over several hours and after activation of neutrophils. Lipopolysaccharide and granulocyte-colony stimulating factor (G-CSF) were administered to 15 and 8 healthy volunteers, respectively and DAO concentrations were measured at different timepoints. DAO antigen levels were also determined in three different subcohorts of patients with culture-proven bacteremia and high C-reactive protein (CRP) levels. DAO concentrations were elevated in a time-dependent manner in serum but not in EDTA or citrate plasma (P < 0.01). Neutrophil activation using phorbol myristate acetate (PMA) and zymosan dose-dependently caused DAO concentrations to be elevated more than 10-fold at both 22°C and 37°C (both P-values <0.001). Administration of LPS to healthy volunteers released DAO from neutrophils (P < 0.001). Of the 55 different bacteremic patients selected from three independent cohorts only 3 (5.4%) showed highly elevated DAO concentrations. Serum DAO concentrations do not accurately reflect circulating enzyme levels but coagulation-induced neutrophil activation and consequently DAO release. Only a few bacteremic patients show high DAO concentrations able to degrade histamine rapidly.
Asunto(s)
Bacteriemia/sangre , D-Aminoácido Oxidasa/sangre , Activación Neutrófila , Neutrófilos/enzimología , Bacteriemia/enzimología , Bacteriemia/inmunología , Biomarcadores/sangre , Coagulación Sanguínea , Estudios Cruzados , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Lipopolisacáridos/administración & dosificación , Activación Neutrófila/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Regulación hacia ArribaRESUMEN
The increase in carbapenem-resistant gram-negative bacteria is a matter of concern due to the limited therapeutic options available. In severe infections caused by these isolates, the rapid detection of the mechanisms of resistance is vital. We described a slightly modified version of the Blue-Carba test, rapid Blue-Carba test, which allows the detection of carbapenemases at 4 h of incubation from a haze of bacterial growth obtained from a positive blood culture. It was able to detect carbapenemase-producing isolates (Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii) with a sensitivity and specificity of 98.1 and 100%, respectively. It is a rapid, easy-to-perform and an inexpensive technique that can be applied to routine laboratories, together with the simultaneous identification by mass spectrometry which would help to screen non-enzymatic carbapenem resistance; this method allows the detection of clinically relevant multidrug-resistant bacteria and the early implementation of accurate therapeutic interventions.
Asunto(s)
Infecciones por Acinetobacter/enzimología , Bacteriemia/enzimología , Proteínas Bacterianas/sangre , Farmacorresistencia Bacteriana Múltiple , Infecciones por Enterobacteriaceae/enzimología , Infecciones por Pseudomonas/enzimología , Resistencia betalactámica , beta-Lactamasas/sangre , Infecciones por Acinetobacter/diagnóstico , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/enzimología , Acinetobacter baumannii/crecimiento & desarrollo , Acinetobacter baumannii/aislamiento & purificación , Antibacterianos/metabolismo , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Argentina , Bacteriemia/diagnóstico , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Proteínas Bacterianas/genética , Carbapenémicos/metabolismo , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Enterobacteriaceae/efectos de los fármacos , Enterobacteriaceae/enzimología , Enterobacteriaceae/crecimiento & desarrollo , Enterobacteriaceae/aislamiento & purificación , Infecciones por Enterobacteriaceae/diagnóstico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Enterobacteriaceae/microbiología , Hospitales Universitarios , Humanos , Inactivación Metabólica , Tipificación Molecular , Infecciones por Pseudomonas/diagnóstico , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/enzimología , Pseudomonas aeruginosa/crecimiento & desarrollo , Pseudomonas aeruginosa/aislamiento & purificación , Sensibilidad y Especificidad , Factores de Tiempo , beta-Lactamasas/genéticaRESUMEN
The human gut microbiome is involved in vital biological functions, such as maintenance of immune homeostasis and modulation of intestinal development and enhanced metabolic capabilities. Disturbances of the intestinal microbiota have been associated with development and progression of inflammatory conditions, including graft-versus-host disease (GVHD). The fucosyltransferase 2 (FUT2) gene produces an enzyme that is responsible for the synthesis of the H antigen in body fluids and on the intestinal mucosa. FUT2 genotype has been shown to modify the gut microbiome. We hypothesized that FUT2 genotype influences risk of GVHD and bacterial translocation after allogeneic hematopoietic stem cell transplantation (HSCT). FUT2 genotype was determined in 150 consecutive patients receiving allogeneic HSCT at our center. We abstracted clinical characteristics and outcomes from the transplantation database. Cumulative risk of any acute GVHD varied by FUT2 genotype, with decreased risk in those with A/A genotype and increased risk in those with G/G genotype. In contrast, the cumulative incidence of bacteremia was increased in those with A/A genotype. We conclude that the FUT2 genotype influences risk of acute GVHD and bacteremia after HSCT. We hypothesize that the mechanisms involve altered intestinal surface glycosylation and microbial composition but this requires additional study.
Asunto(s)
Bacteriemia/genética , Fucosiltransferasas/genética , Microbioma Gastrointestinal , Genotipo , Enfermedad Injerto contra Huésped/genética , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Aloinjertos , Bacteriemia/enzimología , Bacteriemia/etiología , Traslocación Bacteriana/genética , Niño , Preescolar , Bases de Datos Factuales , Femenino , Enfermedad Injerto contra Huésped/enzimología , Enfermedad Injerto contra Huésped/etiología , Humanos , Lactante , Masculino , Factores de Riesgo , Galactósido 2-alfa-L-FucosiltransferasaRESUMEN
OBJECTIVE: To investigate whether expression of genes associated with inflammation and activity of indoleamine-2,3-dioxygenase (IDO) correlated with disease status and prevalence of bacteremia in post-partum dairy cattle with and without acute puerperal metritis (APM). PROCEDURES: Blood was collected from cattle with APM and control cattle matched by parity and days in milk. Leukocytes were isolated and expression of 6 genes was quantified. Activity of IDO was measured in serum with higher performance liquid chromatography (HPLC). RESULTS: The relative expression of IL-1ß in cattle with APM was significantly lower than that in controls. IDO activity was not significantly different between bacteremic and non-bacteremic cattle CONCLUSIONS AND CLINICAL RELEVANCE: The expression of IL-1ß was lower in cattle with APM. The lower levels of IL-1ß expression in PBMCs of cattle with APM suggest impaired inflammatory responses and may contribute to the development of the disease in this population of animals.
Asunto(s)
Bacteriemia/veterinaria , Enfermedades de los Bovinos/enzimología , Enfermedades de los Bovinos/metabolismo , Endometritis/veterinaria , Regulación de la Expresión Génica/fisiología , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Infección Puerperal/veterinaria , Animales , Bacteriemia/enzimología , Bacteriemia/metabolismo , Bovinos , Endometritis/enzimología , Endometritis/metabolismo , Femenino , Inflamación/genética , Inflamación/metabolismo , Interleucina-1beta/metabolismo , Leucocitos/metabolismo , Periodo Posparto/metabolismo , Embarazo , Infección Puerperal/enzimología , Infección Puerperal/metabolismoRESUMEN
Studies on mouse model of generalized Staphylococcus epidermidis infection have demonstrated that erythrocytes more often contained microorganisms with pronounced antihemoglobin activity and less frequently with hemolytic activity. Infection with S. epidermidis strains characterized by pronounced hemolytic or antihemoglobin activities was associated with inhibition of erythrocyte catalase and superoxide dismutase activities in all cases, except infection with strains with high antihemoglobin activity, when superoxide dismutase activity increased.
Asunto(s)
Bacteriemia/sangre , Catalasa/sangre , Eritrocitos/microbiología , Infecciones Estafilocócicas/sangre , Staphylococcus epidermidis/fisiología , Superóxido Dismutasa/sangre , Animales , Bacteriemia/enzimología , Bacteriemia/microbiología , Catalasa/antagonistas & inhibidores , Eritrocitos/enzimología , Hemoglobinas , Hemólisis , Masculino , Ratones , Especificidad de la Especie , Infecciones Estafilocócicas/enzimología , Infecciones Estafilocócicas/microbiología , Staphylococcus epidermidis/clasificación , Staphylococcus epidermidis/patogenicidad , Superóxido Dismutasa/antagonistas & inhibidores , VirulenciaRESUMEN
Occurrence of carbapenemase-producing organisms, including New Delhi metallo-ß-lactamase-1 (NDM-1) is increasingly reported worldwide. The aim of this study was to assess the distribution of carbapenemase producers among multidrug-resistant Gram-negative bacteria isolated from blood cultures. All carbapenem-resistant strains collected from December 2011 to December 2012 were analyzed. Presence of carbapenemases was assessed with combined disc test and Carba NP test followed by polymerase chain reaction for carbapenemase genes. Altogether, 30 strains were detected, of which 7 were positive for VIM (23.3%), 6 for NDM-1 (20%), 5 for IMP (16.7%), and KPC was present in one isolate (3.3%). Four Pseudomonas aeruginosa strains were found to produce more than one carbapenemase. We also present the case report of a patient with Acinetobacter baumannii ventilator-associated pneumonia, followed by sepsis due to Enterococcus faecalis and pan-resistant NDM-1-producing P. aeruginosa. Despite the inappropriate therapy, the patient was successfully treated. This is the first report of NDM-1-producing strains in Slovakia and it contributes to a number of studies mapping the distribution of carbapenemase producers in Europe.
Asunto(s)
Bacteriemia/enzimología , Farmacorresistencia Bacteriana Múltiple , Bacterias Gramnegativas/enzimología , Infecciones por Bacterias Gramnegativas/enzimología , beta-Lactamasas/análisis , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/aislamiento & purificación , Adulto , Antibacterianos/uso terapéutico , Bacteriemia/epidemiología , Bacteriemia/microbiología , Coinfección , Pruebas Antimicrobianas de Difusión por Disco , Farmacorresistencia Bacteriana Múltiple/genética , Quimioterapia Combinada , Enterococcus faecalis/aislamiento & purificación , Genes Bacterianos , Bacterias Gramnegativas/genética , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Neumonía Asociada al Ventilador/tratamiento farmacológico , Neumonía Asociada al Ventilador/microbiología , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Eslovaquia , beta-Lactamasas/genéticaRESUMEN
Infections, microbe sampling and occasional leakage of commensal microbiota and their products across the intestinal epithelial cell layer represent a permanent challenge to the intestinal immune system. The production of reactive oxygen species by NADPH oxidase is thought to be a key element of defense. Patients suffering from chronic granulomatous disease are deficient in one of the subunits of NADPH oxidase. They display a high incidence of Crohn's disease-like intestinal inflammation and are hyper-susceptible to infection with fungi and bacteria, including a 10-fold increased risk of Salmonellosis. It is not completely understood which steps of the infection process are affected by the NADPH oxidase deficiency. We employed a mouse model for Salmonella diarrhea to study how NADPH oxidase deficiency (Cybb (-/-)) affects microbe handling by the large intestinal mucosa. In this animal model, wild type S. Typhimurium causes pronounced enteropathy in wild type mice. In contrast, an avirulent S. Typhimurium mutant (S.Tm(avir); invGsseD), which lacks virulence factors boosting trans-epithelial penetration and growth in the lamina propria, cannot cause enteropathy in wild type mice. We found that Cybb (-/-) mice are efficiently infected by S.Tm(avir) and develop enteropathy by day 4 post infection. Cell depletion experiments and infections in Cybb (-/-) Myd88 (-/-) mice indicated that the S.Tm(avir)-inflicted disease in Cybb (-/-) mice hinges on CD11c(+)CX3CR1(+) monocytic phagocytes mediating colonization of the cecal lamina propria and on Myd88-dependent proinflammatory immune responses. Interestingly, in mixed bone marrow chimeras a partial reconstitution of Cybb-proficiency in the bone marrow derived compartment was sufficient to ameliorate disease severity. Our data indicate that NADPH oxidase expression is of key importance for restricting the growth of S.Tm(avir) in the mucosal lamina propria. This provides important insights into microbe handling by the large intestinal mucosa and the role of NADPH oxidase in maintaining microbe-host mutualism at this exposed body surface.
Asunto(s)
Bacteriemia/microbiología , Sistemas de Secreción Bacterianos , Colitis/microbiología , NADPH Oxidasas/deficiencia , Salmonelosis Animal/complicaciones , Salmonella typhimurium/fisiología , Animales , Bacteriemia/enzimología , Bacteriemia/inmunología , Antígenos CD11/metabolismo , Colitis/enzimología , Colitis/inmunología , Regulación Enzimológica de la Expresión Génica , Mucosa Intestinal/microbiología , Ratones , Monocitos/inmunología , Monocitos/metabolismo , Mutación , Factor 88 de Diferenciación Mieloide/metabolismo , NADPH Oxidasas/metabolismo , Salmonella typhimurium/genéticaRESUMEN
A reduction of the neutrophil migration into the site of infection during cecal ligation and puncture-induced sepsis increases host mortality. Inhibition of heme oxygenase (HO) prevents this neutrophil paralysis and improves host survival in the cecal ligation and puncture model. Taking into account that almost 50% of all sepsis cases are a consequence of pneumonia, we designed the present study to determine the role of HO in an experimental model of pneumonia-induced sepsis. The objective of this study was to evaluate whether the inhibition of HO improves the outcome and pathophysiologic changes of sepsis induced by an intratracheal instillation of Klebsiella pneumoniae. The pretreatment of mice subjected to pneumonia-induced sepsis with ZnDPBG (zinc deuteroporphyrin 2,4-bis glycol), a nonspecific HO inhibitor, increased the number of neutrophils in the bronchoalveolar spaces, reduced the bacterial load at the site of infection, and prevented the upregulation of CD11b and the downregulation of CXCR2 on blood neutrophils. Moreover, the pretreatment with ZnDPBG decreased alveolar collapse, attenuating the deleterious changes in pulmonary mechanics and gas exchanges and, as a consequence, improved the survival rate of mice from 0% to â¼20%. These results show that heme oxygenase is involved in the pathophysiology of pneumonia-induced sepsis and suggest that HO inhibitors could be helpful for the management of this disease.
Asunto(s)
Bacteriemia/enzimología , Hemo Oxigenasa (Desciclizante)/antagonistas & inhibidores , Enfermedades del Sistema Inmune/enzimología , Infecciones por Klebsiella/enzimología , Trastornos Leucocíticos/enzimología , Neumonía Bacteriana/enzimología , Alveolos Pulmonares/enzimología , Lesión Pulmonar Aguda/prevención & control , Animales , Bacteriemia/microbiología , Bronquios/enzimología , Quimiocinas/metabolismo , Forma MB de la Creatina-Quinasa/metabolismo , Citocinas/metabolismo , Deuteroporfirinas/farmacología , Inhibidores Enzimáticos/farmacología , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae , Ratones , Neumonía Bacteriana/microbiología , Receptores de Interleucina-8B/metabolismoRESUMEN
Sepsis remains the leading cause of death in critically ill patients, despite modern advances in critical care. Intestinal barrier dysfunction may lead to secondary bacterial translocation and the development of the multiple organ dysfunction syndrome during sepsis. Cyclooxygenase (COX)-2 is highly upregulated in the intestine during sepsis, and we hypothesized that it may be critical in the maintenance of intestinal epithelial barrier function during peritonitis-induced polymicrobial sepsis. COX-2(-/-) and COX-2(+/+) BALB/c mice underwent cecal ligation and puncture (CLP) or sham surgery. Mice chimeric for COX-2 were derived by bone marrow transplantation and underwent CLP. C2BBe1 cells, an intestinal epithelial cell line, were treated with the COX-2 inhibitor NS-398, PGD(2), or vehicle and stimulated with cytokines. COX-2(-/-) mice developed exaggerated bacteremia and increased mortality compared with COX-2(+/+) mice following CLP. Mice chimeric for COX-2 exhibited the recipient phenotype, suggesting that epithelial COX-2 expression in the ileum attenuates bacteremia following CLP. Absence of COX-2 significantly increased epithelial permeability of the ileum and reduced expression of the tight junction proteins zonula occludens-1, occludin, and claudin-1 in the ileum following CLP. Furthermore, PGD(2) attenuated cytokine-induced hyperpermeability and zonula occludens-1 downregulation in NS-398-treated C2BBe1 cells. Our findings reveal that absence of COX-2 is associated with enhanced intestinal epithelial permeability and leads to exaggerated bacterial translocation and increased mortality during peritonitis-induced sepsis. Taken together, our results suggest that epithelial expression of COX-2 in the ileum is a critical modulator of tight junction protein expression and intestinal barrier function during sepsis.
Asunto(s)
Ciclooxigenasa 2/deficiencia , Ciclooxigenasa 2/genética , Mucosa Intestinal/enzimología , Mucosa Intestinal/inmunología , Sepsis/inmunología , Sepsis/mortalidad , Animales , Bacteriemia/enzimología , Bacteriemia/inmunología , Bacteriemia/mortalidad , Células CACO-2 , Permeabilidad de la Membrana Celular/genética , Permeabilidad de la Membrana Celular/inmunología , Ciclooxigenasa 2/biosíntesis , Femenino , Humanos , Íleon/enzimología , Íleon/inmunología , Íleon/microbiología , Mucosa Intestinal/microbiología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Peritonitis/enzimología , Peritonitis/inmunología , Peritonitis/mortalidad , Sepsis/enzimologíaRESUMEN
OBJECTIVE: Recently, CTX-M-15-producing Enterobacteriaceae has disseminated worldwide. To better understand the success of CTX-M-15-type extended-spectrum ß-lactamase, we compared the CTX-M-15-producing Escherichia coli and Klebsiella pneumoniae isolates with CTX-M-14-producing E. coli and K. pneumoniae isolates that had been more prevalent before the recent increase of CTX-M-15 in Korea. METHODS: Eighty-nine CTX-M-producing E. coli bloodstream infection isolates and 33 K. pneumoniae bloodstream infection isolates were collected in 2008 from nine hospitals in Korea. In vitro susceptibility testing and multilocus sequence typing were performed for all isolates. Phylogenetic groupings and distribution of virulence determinants and addiction systems were examined for only E. coli isolates. RESULTS: Among the 89 CTX-M-producing E. coli isolates, 54 isolates (60.7%) contained bla(CTx-M-15) and bla(CTx-M-14) was identified in 31 isolates (34.8%). Among 33 CTX-M-producing K. pneumoniae isolates, bla(CTx-M-14) and bla(CTx-M-15) were identified in 18 (54.5%) and 15 (45.5%) isolates, respectively. While CTX-M-14- and CTX-M-15-producing E. coli isolates displayed similar antimicrobial resistance rates, CTX-M-15-producing K. pneumoniae isolates showed significantly higher resistance rates of ciprofloxacin and piperacillin-tazobactam than CTX-M-14-producing isolates. ST131 and ST405 were the main clones in both CTX-M-14- and CTX-M-15-producing E. coli isolates. Although the frequency of virulence determinants was similar between two E. coli groups, ST131 and ST405 isolates producing CTX-M-15 showed higher frequency of determinants. In addition, CTX-M-15-producing E. coli isolates showed higher prevalence of addiction systems, particularly vagCD. ST405 showed the highest prevalence rates among main E. coli clones. In K. pneumoniae, ST15 and ST11, with high resistance rates, were the main clones of CTX-M-15-producing isolates, but no main clones was found among CTX-M-14-producing isolates because of extreme diversity. CONCLUSIONS: Rapid increase of CTX-M-15-producing E. coli isolates was due to certain clone with high frequency of virulence determinants and addiction systems. High antimicrobial resistance rates of CTX-M-15-producing K. pneumoniae isolates may contribute to their increase.
Asunto(s)
Farmacorresistencia Bacteriana Múltiple/genética , Escherichia coli/genética , Klebsiella pneumoniae/genética , beta-Lactamasas/genética , Antibacterianos/farmacología , Bacteriemia/tratamiento farmacológico , Bacteriemia/enzimología , Bacteriemia/microbiología , Bases de Datos de Ácidos Nucleicos , Escherichia coli/efectos de los fármacos , Escherichia coli/patogenicidad , Humanos , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/patogenicidad , Reacción en Cadena de la Polimerasa , República de CoreaRESUMEN
BACKGROUND: Coagulase-negative staphylococci (CoNS) are the most common cause of late-onset sepsis in neonatal intensive care unit settings. Historically, authors have questioned the clinical significance of these bacteremia episodes. Recently, clusters of CoNS bacteremia associated with significant morbidity have been reported. The frequency and importance of these clusters of bacteremia and their associated morbidity remains unclear. OBJECTIVE: We studied a prolonged cluster of 52 cases of persistent CoNS bacteremia in a level III neonatal intensive care unit to clarify risk factors, morbidity and outcomes associated with persistent CoNS bacteremia. STUDY DESIGN: A retrospective case-control study of infants with CoNS bacteremia >48 h after initiation of appropriate antibiotics and gestational age-matched control infants was performed. We reviewed patient characteristics prior to and during bacteremia, and outcomes at discharge or death. RESULTS: Persistently infected infants were significantly more likely to have greater duration of exposure to parenteral nutrition, hydrocortisone, antibiotics, and mechanical ventilation prior to infection. Persistently infected infants were significantly more likely than controls to experience feeding intolerance and to require inotropic support, increased respiratory support, and blood product transfusion during bacteremia. Infants with persistent CoNS bacteremia took longer to achieve full enteral feeds, had higher rates of chronic lung disease and increased length of stay compared to controls. No significant difference in mortality was noted. CONCLUSIONS: Persistent CoNS bacteremia is associated with clinically significant morbidity including feeding intolerance, respiratory failure, blood transfusion and chronic lung disease in this patient population. This impacts hospital course, increases length of stay and impacts medical needs after discharge. During this study, CoNS bacteremia was difficult to clinically eradicate despite in vitro antibiotic susceptibility.
Asunto(s)
Bacteriemia/epidemiología , Coagulasa/metabolismo , Infecciones Estafilocócicas/epidemiología , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/enzimología , Estudios de Casos y Controles , Femenino , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Masculino , Morbilidad , Nebraska/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Infecciones Estafilocócicas/enzimología , Infecciones Estafilocócicas/patologíaRESUMEN
Indoleamine 2,3-dioxygenase (IDO), which is the rate-limiting enzyme for tryptophan (trp) catabolism, may play a critical role in various inflammatory disorders. Recent studies on trauma patients have suggested that the degradation of trp is associated with the development of sepsis. The role of IDO activity in bacteremic patients is unclear. We studied IDO activity in 132 patients with bacteremia caused by Staphylococcus aureus, Streptococcus pneumoniae, beta-hemolytic streptococcae, or Eschericia coli. The serum concentrations of trp and its metabolite kynurenine (kyn) were measured by reverse-phase high-performance liquid chromatography 1 to 4 days after the positive blood culture and on recovery. The kyn-to-trp ratio (kyn/trp), reflecting the activity of the IDO enzyme, was calculated. The maximum value in the ratio for every patient during 1 to 4 days after positive blood culture was used in analysis. The maximum kyn/trp ratio was significantly higher in nonsurvivors versus those who survived (193.7 vs. 82.4 micromol/mmol; P = 0.001). The AUC(ROC) of maximal kyn/trp in the prediction of case fatality was 0.75 (95% confidence interval, 0.64-0.87), and the kyn/trp ratio at a cutoff level of 120 micromol/mmol showed 83% sensitivity and 69% specificity for fatal disease. A kyn/trp ratio greater than 120 micromol/mmol was associated with increased risk of death versus low (Asunto(s)
Bacteriemia/sangre
, Bacteriemia/enzimología
, Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo
, Adulto
, Anciano de 80 o más Años
, Bacteriemia/mortalidad
, Cromatografía Líquida de Alta Presión
, Femenino
, Humanos
, Quinurenina/sangre
, Masculino
, Persona de Mediana Edad
, Triptófano/sangre
, Adulto Joven
RESUMEN
OBJECTIVE: To study the risk factors for bacteremia caused by Escherichia coli (E. coli) or Klebsiella pneumoniae (K. pneumoniae) producing extended-spectrum beta-lactamase (ESBL) and their outcome. METHODS: A case-control study was conducted in King Abdul-Aziz National Guard Hospital, Al-Ahsa, Kingdom of Saudi Arabia from January 2006 through December 2007. All adult patients for whom culture results were positive for E. coli or K. pneumoniae were eligible. Twenty-nine patients with ESBL producing bacteremia (cases) were compared with 80 patients with non-ESBL producing bacteremia controls. Hospital mortality was the primary end point. Univariable and multivariable logistic regression were performed to analyze risk factors for ESBL bacteremia and its 30-day mortality. RESULTS: A total of 109 patients with bacteremia were enrolled that included 29 cases and 80 controls. Forty-nine percent of the patients were male. The mean age was 60.2+/-21.1 years. Nosocomial infection was the only independent risk factor for bacteremia due to ESBL-producing pathogens (odds ratio [OR] 3.40, 95% confidence interval [CI] 1.14-8.44, p=0.02). Overall 30-day mortality was 22%, and was similar in both groups. The nosocomial infection (OR 3.20, 95% CI 1.48-6.94, p=0.01), presentation with septic shock (OR 48.88, 95% CI 6.01-397.32, p=0.004), and intensive care unit care (OR 7.40, 95% CI 1.94 -28.34, p=0.001) were the independent risk factors for 30-day mortality. CONCLUSION: The ESBL rate is high in our study among the bacteremic patients. Nosocomial infection is identified both as a risk factor for ESBL bacteremia and mortality.
Asunto(s)
Bacteriemia/enzimología , Escherichia coli/enzimología , Klebsiella pneumoniae/enzimología , beta-Lactamasas/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Bacteriemia/mortalidad , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Factores de Riesgo , Arabia SauditaRESUMEN
Hydrogen sulfide (H(2)S) up-regulates inflammatory response in several inflammatory diseases. However, to date, little is known about the molecular mechanism by which H(2)S provokes the inflammatory response in sepsis. Thus, the aim of this study was to investigate the signaling pathway underlying the proinflammatory role of H(2)S in cecal ligation and puncture (CLP)-induced sepsis. Male Swiss mice were subjected to CLP and treated with dl-propargylglycine (PAG; 50 mg/kg i.p., an inhibitor of H(2)S formation), NaHS (10 mg/kg, i.p., an H(2)S donor), or saline. PAG was administered 1 h before CLP, whereas NaHS was given at the time of CLP. CLP-induced sepsis resulted in a time-dependent increase in the synthesis of endogenous H(2)S. Maximum phosphorylation of ERK1/2 and degradation of IkappaBalpha in lung and liver were observed 4 h after CLP. Inhibition of H(2)S formation by PAG significantly reduced the phosphorylation of ERK1/2 in lung and liver 4 h after CLP, coupled with decreased degradation of IkappaBalpha and activation of NF-kappaB. In contrast, injection of NaHS significantly enhanced the activation of ERK1/2 in lung and liver, therefore leading to a further rise in tissue NF-kappaB activity. As a result, pretreatment with PAG significantly reduced the production of cytokines and chemokines in sepsis, whereas exogenous H(2)S greatly increased it. In addition, pretreatment with PD98059, an inhibitor of ERK kinase (MEK-1), significantly prevented NaHS from aggravating systemic inflammation in sepsis. In conclusion, the present study shows for the first time that H(2)S may regulate systemic inflammatory response in sepsis via ERK pathway.
Asunto(s)
Sulfuro de Hidrógeno/metabolismo , Mediadores de Inflamación/fisiología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Sepsis/enzimología , Sepsis/patología , Transducción de Señal/inmunología , Animales , Bacteriemia/enzimología , Bacteriemia/metabolismo , Bacteriemia/patología , Ciego/cirugía , Activación Enzimática/inmunología , Sulfuro de Hidrógeno/sangre , Mediadores de Inflamación/sangre , Ligadura , Masculino , Ratones , Proteína Quinasa 1 Activada por Mitógenos/fisiología , Proteína Quinasa 3 Activada por Mitógenos/fisiología , FN-kappa B/metabolismo , FN-kappa B/fisiología , Peritonitis/enzimología , Peritonitis/metabolismo , Peritonitis/patología , Punciones , Sepsis/inmunología , Sepsis/metabolismo , Regulación hacia Arriba/inmunologíaRESUMEN
Clostridium perfringens is a Gram-positive bacterium responsible for bacteremia, gas gangrene, and occasionally food poisoning. Its genome encodes three sialidases, nanH, nanI, and nanJ, that are involved in the removal of sialic acids from a variety of glycoconjugates and that play a role in bacterial nutrition and pathogenesis. Recent studies on trypanosomal (trans-) sialidases have suggested that catalysis in all sialidases may proceed via a covalent intermediate similar to that of other retaining glycosidases. Here we provide further evidence to support this suggestion by reporting the 0.97A resolution atomic structure of the catalytic domain of the C. perfringens NanI sialidase, and complexes with its substrate sialic acid (N-acetylneuramic acid) also to 0.97A resolution, with a transition-state analogue (2-deoxy-2,3-dehydro-N-acetylneuraminic acid) to 1.5A resolution, and with a covalent intermediate formed using a fluorinated sialic acid analogue to 1.2A resolution. Together, these structures provide high resolution snapshots along the catalytic pathway. The crystal structures suggested that NanI is able to hydrate 2-deoxy-2,3-dehydro-N-acetylneuraminic acid to N-acetylneuramic acid. This was confirmed by NMR, and a mechanism for this activity is suggested.
Asunto(s)
Clostridium perfringens/enzimología , Neuraminidasa/química , Ácidos Siálicos/química , Bacteriemia/enzimología , Catálisis , Clostridium perfringens/patogenicidad , Cristalografía por Rayos X , Enfermedades Transmitidas por los Alimentos/enzimología , Gangrena Gaseosa/enzimología , Glicoconjugados/química , Glicoconjugados/metabolismo , Humanos , Resonancia Magnética Nuclear Biomolecular , Estructura Terciaria de Proteína , Ácidos Siálicos/metabolismoRESUMEN
Cardiovascular dysfunction in septic shock (SS) is ascribed to the release of inflammatory mediators. Norepinephrine (NE) is often administered to treat low MAP in SS. We recently found that lysozyme c (Lzm-S) released from leukocytes was a mediator of myocardial depression in an Escherichia coil model of SS in dogs. This effect can be blocked in an in vitro preparation by chitobiose, a competitive inhibitor of Lzm-S. In the present study, we examined whether chitobiose treatment can reverse myocardial depression and obviate NE requirements in two respective canine E. coli preparations. In a 6-h study, we administered chitobiose after 3.5 h of E. coli bacteremia and compared stroke work (SW) and MAP at 6 h with a sepsis control group. In a 12-h study, we determined whether chitobiose treatment can reduce the need for NE requirements during 12 h of bacteremia. In the latter study, either chitobiose or NE was given when MAP decreased approximately 20% from the presepsis value in respective groups. In anesthetized, mechanically ventilated dogs, we monitored hemodynamic parameters during continuous E. coli infusion. In the 6-h study, chitobiose improved SW and MAP at the 6-h period as compared with the nontreated sepsis group. In the 12-h study, SW and MAP increased after chitobiose without the necessity of NE administration. These results suggest that inhibitors of Lzm-S such as chitobiose may improve myocardial depression and reduce the need for NE requirements in SS.
Asunto(s)
Cardiomiopatías/tratamiento farmacológico , Disacáridos/farmacología , Inhibidores Enzimáticos/farmacología , Infecciones por Escherichia coli/tratamiento farmacológico , Escherichia coli , Muramidasa/antagonistas & inhibidores , Norepinefrina/farmacología , Choque Séptico/tratamiento farmacológico , Vasoconstrictores/farmacología , Animales , Bacteriemia/tratamiento farmacológico , Bacteriemia/enzimología , Bacteriemia/fisiopatología , Cardiomiopatías/enzimología , Cardiomiopatías/fisiopatología , Perros , Infecciones por Escherichia coli/enzimología , Infecciones por Escherichia coli/fisiopatología , Humanos , Mediadores de Inflamación/metabolismo , Masculino , Choque Séptico/enzimología , Choque Séptico/fisiopatología , Volumen Sistólico/efectos de los fármacos , Factores de TiempoRESUMEN
The purpose of this study was to determine the prevalence of two type III secretion effector proteins, exoU and exoS from bloodstream isolates of hospitalized patients with Pseudomonas aeruginosa (PSA) bacteremia, to characterize antimicrobial susceptibility patterns, and to compare mortality rates. PSA bloodstream isolates and antibiotic susceptibility profiles were collected from a university-affiliated hospital. ExoS and exoU genes were detected by polymerase chain reaction. Hospital mortality was assessed by medical chart review. 119 of 122 (97.5%) PSA bloodstream isolates contained either the exoS or exoU genes. ExoS was the most prevalent (n=86; 70.5%) followed by exoU (n=31; 25.4%), both genes (n=2; 1.6%) or neither gene (n=3; 2.5%). Isolates containing the exoU gene were significantly more likely to be resistant to cefepime, ceftazidime, piperacillintazobactam, carbapenems, fluoroquinolones, and gentamicin (p<0.05 for all). Mortality was high in patients with PSA bacteremia and did not differ among patients infected with the exoS isolates (n=37; 43%) or exoU isolates (n=11; 35%). One of two type III secretion effector proteins were almost universally present in PSA bloodstream isolates. Isolates containing the exoU gene were more likely to be resistant to multiple antibiotics.
Asunto(s)
ADP Ribosa Transferasas/genética , Bacteriemia/enzimología , Proteínas Bacterianas/genética , Toxinas Bacterianas/genética , Farmacorresistencia Bacteriana Múltiple/genética , Infecciones por Pseudomonas/enzimología , Infecciones por Pseudomonas/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Bacteriemia/epidemiología , Bacteriemia/genética , Southern Blotting , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Prevalencia , Infecciones por Pseudomonas/genética , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/enzimología , Pseudomonas aeruginosa/genéticaRESUMEN
OBJECTIVES: To evaluate the specificity and sensitivity of the clinical criteria widely used to differentiate true coagulase-negative staphylococcal (CoNS) bacteremia from contamination, using pulsed-field gel electrophoresis (PFGE) as the reference test. DESIGN: The study sample consisted of 79 CoNS isolates recovered from cultures of blood from 38 patients. Medical charts of the patients were reviewed for demographic and clinical information. The relatedness of CoNS strains recovered from 2 or more successive blood cultures was analyzed by PFGE. Patients from whom similar strains were recovered were assumed to have true bacteremia, whereas patients from whom different strains were recovered were considered to have contaminated blood cultures. The clinical criteria comprised Centers for Disease Control and Prevention (CDC) surveillance definitions for bloodstream infection (BSI), as well as an alternative criterion based on the presence of fever, the presence of leukocytosis, the absence of another recognized infection, and the recovery of CoNS from 2 or more successive blood cultures. RESULTS: Nineteen (50%) of the 38 patients had bacteremia due to similar strains; the remaining patients had bacteremia due to different strains. Criterion 2a of the CDC definition for BSI had a sensitivity of 100% and a specificity of 31.6% for distinguishing between true bacteremia and contamination. CDC criterion 2b had a sensitivity of 78.9% and a specificity of 52.6%. CONCLUSIONS: Molecular typing correlated poorly with the clinical criteria for true bacteremia. In view of the limited applicability of clinical criteria, more studies are needed to improve them. Periodic cross-sectional studies based on PFGE findings might be useful to estimate local contamination rates in an institution, which in turn can be used to improve the accuracy of the clinical diagnosis of bacteremia.