Proteomic study revealed cellular assembly and lipid metabolism dysregulation in sepsis secondary to community-acquired pneumonia.

Sepsis is a life-threatening disorder characterized by organ dysfunction and a major cause of mortality worldwide. The major challenge in studying sepsis is its diversity in such factors as age, source of infection and etiology. Recently, genomic and proteomic approaches have improved our understanding of its complex pathogenesis. In the present study, we use quantitative proteomics to evaluate the host proteome response in septic patients secondary to community-acquired pneumonia (CAP). Samples obtained at admission and after 7 days of follow-up were analyzed according to the outcomes of septic patients. The patients' proteome profiles were compared with age- and gender-matched healthy volunteers. Bioinformatic analyses of differentially expressed proteins showed alteration in the cytoskeleton, cellular assembly, movement, lipid metabolism and immune responses in septic patients. Actin and gelsolin changes were assessed in mononuclear cells using immunofluorescence, and a higher expression of gelsolin and depletion of actin were observed in survivor patients. Regarding lipid metabolism, changes in cholesterol, HDL and apolipoproteins were confirmed using enzymatic colorimetric methods in plasma. Transcriptomic studies revealed a massive change in gene expression in sepsis. Our proteomic results stressed important changes in cellular structure and metabolism, which are possible targets for future interventions of sepsis.

Rapidly Progressive Seeding of a Community Acquired Pathogen in an Immune-competent Host--End Organ Damage from Head to Bone.

This report describes a 64-years-old male patient that presented to our hospital with a chief complaint of acute worsening of his usual chronic lower back pain, progressive weakness in lower extremities and subjective fevers at home. Spine CT failed to demonstrate any infectious foci but showed partially visualized lung cavitary lesion and renal pole abnormalities. Blood cultures grew methicillin-sensitive Staphylococcus Aureus (MSSA). Transthoracic echocardiogram (TTE) showed no signs of infective endocarditis (IE). Later, the patient experienced an acute deterioration on clinical status and examination showed development of a new murmur. He also developed new hemiparesis with up-going babinski reflex. A head MRI showed multiple infarcts. MRI spine displayed osteomyelitis at T12-L1. Cerebro-spinal fluid was positive for meningitis. A transesophageal echocardiogram (TEE) was performed demonstrating new severe mitral and mild tricuspid regurgitations with a definitive 1.5 cm mobile vegetation on posterior mitral leaflet. We present is a very interesting case of a rapidly progressive MSSA infection. MSSA meningitis is a rare disease; there are only few reported cases in the literature to date. We describe a case of MSSA bacteremia, of questionable source, that resulted in MSSA endocarditis affecting right and left heart in a patient who did not have a history of intravenous drug use (IVDU) or immunosuppression. The case was complicated by septic emboli to systemic circulation involving the kidneys, vertebral spine (osteomyelitis), lungs and brain with consequent meningitis and stroke. Even when MSSA infections are well known, to our knowledge there are no previous case reports describing such an acute-simultaneous-manifestation of multi-end-organ failure, including meningitis and stroke. These latter are rarely reported, even individually.

Community-acquired necrotizing pneumonia caused by methicillin-resistant Staphylococcus aureus ST30-SCCmecIVc-spat019-PVL positive in San Antonio de Areco, Argentina.

Community-acquired methicillin-resistant Staphylococcus aureus is the first cause of skin and soft tissue infections, but can also produce severe diseases such as bacteremia, osteomyelitis and necrotizing pneumonia. Some S. aureus lineages have been described in cases of necrotizing pneumonia worldwide, usually in young, previously healthy patients. In this work, we describe a fatal case of necrotizing pneumonia due to community-acquired methicillin-resistant S. aureus clone ST30-SCCmecIVc-spat019-PVL positive in an immunocompetent adult patient.

Community-associated methicillin-resistant Staphylococcus aureus skin and soft tissue infections in a pediatric hospital in Argentina.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) emerged at the Pediatric Hospital of Misiones Province, north Argentina, in 2003 as a cause of community-acquired (CA) infections, mostly associated with skin and soft tissue infections (SSTIs). This study aimed to assess the microbiological, epidemiological, and clinical features of CA-MRSA SSTIs treated at the hospital. METHODOLOGY: From 2003 through 2006, a longitudinal study on CA-MRSA SSTIs was conducted. Clinical, bacteriological, and molecular data were collected and analyzed by multiple correspondences and cluster analysis (MCCA). RESULTS: A total of 138 children were enrolled; 55.8% of the children required hospitalization. The main clinical presentation was abscesses (51%). Antibiotic therapy in the previous six months was registered in 41% of the patients, and 72% of the patients had relatives with similar symptoms. Resistance to non-b-lactam antibiotics was found in less than 12% of patients. All 44 isolates carried staphylococcal cassette chromosomemec (SCCmec) type IV, and 30/44 had Panton-Valentine leucocidin (PVL) coding genes. Six pulsed-field gel electrophoresis (PFGE) patterns were detected from 17 isolates. MCCA hierarchic classification resulted in four distinctive patient classes (new variable). No relationship could be observed regarding the PVL detection, as PVL (+) isolates were detected in all classes; the same lack of significance was observed concerning the distribution of resistance to non-ß-lactam antibiotics. CONCLUSIONS: This study increases the understanding and knowledge about CA-MRSA skin and soft tissue infections in pediatric patients. Continuous efforts should be made to control this significant public health problem.

Success stories about severe pneumonia caused by Panton-Valentine leucocidin-producing Staphylococcus aureus

We describe three cases of community-acquired necrotizing pneumonia which were caused by Panton-Valentine leucocidin-producing strains of Staphylococcus aureus (one of them methicillin sensitive). All cases were successfully treated without any sequelae for the patients due to the prompt initiation of adequate antimicrobial therapy. High suspicion toward this fatal pathogen was the key to the successful outcome of the patients.

Success stories about severe pneumonia caused by Panton-Valentine leucocidin-producing Staphylococcus aureus.

We describe three cases of community-acquired necrotizing pneumonia which were caused by Panton-Valentine leucocidin-producing strains of Staphylococcus aureus (one of them methicillin sensitive). All cases were successfully treated without any sequelae for the patients due to the prompt initiation of adequate antimicrobial therapy. High suspicion toward this fatal pathogen was the key to the successful outcome of the patients.

Prevalence and clinical features of respiratory syncytial virus in children hospitalized for community-acquired pneumonia in northern Brazil.

BACKGROUND: Childhood pneumonia and bronchiolitis is a leading cause of illness and death in young children worldwide with Respiratory Syncytial Virus (RSV) as the main viral cause. RSV has been associated with annual respiratory disease outbreaks and bacterial co-infection has also been reported. This study is the first RSV epidemiological study in young children hospitalized with community-acquired pneumonia (CAP) in Belém city, Pará (Northern Brazil). METHODS: With the objective of determining the prevalence of RSV infection and evaluating the patients' clinical and epidemiological features, we conducted a prospective study across eight hospitals from November 2006 to October 2007. In this study, 1,050 nasopharyngeal aspirate samples were obtained from hospitalized children up to the age of three years with CAP, and tested for RSV antigen by direct immunofluorescence assay and by Reverse Transcription Polymerase Chain Reaction (RT-PCR) for RSV Group identification. RESULTS: RSV infection was detected in 243 (23.1%) children. The mean age of the RSV-positive group was lower than the RSV-negative group (12.1 months vs 15.5 months, p<0.001) whereas gender distribution was similar. The RSV-positive group showed lower means of C-reactive protein (CRP) in comparison to the RSV-negative group (15.3 vs 24.0 mg/dL, p<0.05). Radiological findings showed that 54.2% of RSV-positive group and 50.3% of RSV-negative group had interstitial infiltrate. Bacterial infection was identified predominantly in the RSV-positive group (10% vs 4.5%, p<0.05). Rhinorrhea and nasal obstruction were predominantly observed in the RSV-positive group. A co-circulation of RSV Groups A and B was identified, with a predominance of Group B (209/227). Multivariate analysis revealed that age under 1 year (p<0.015), CRP levels under 48 mg/dL (p<0.001) and bacterial co-infection (p<0.032) were independently associated with the presence of RSV and, in the analyze of symptoms, nasal obstruction were independently associated with RSV-positive group (p<0.001). CONCLUSION: The present study highlights the relevance of RSV infection in hospitalized cases of CAP in our region; our findings warrant the conduct of further investigations which can help design strategies for controlling the disease.

Soluble RAGE as a severity marker in community acquired pneumonia associated sepsis.

BACKGROUND: Community-acquired pneumonia (CAP) is considered the most important cause of death from infectious disease in developed countries. Severity assessment scores partially address the difficulties in identifying high-risk patients. A lack of specific and valid pathophysiologic severity markers affect early and effective sepsis therapy. HMGB-1, sRAGE and RAGE have been involved in sepsis and their potential as severity markers has been proposed. The aim of this study was to evaluate HMGB-1, RAGE and sRAGE levels in patients with CAP-associated sepsis and determine their possible association with clinical outcome. METHOD: We evaluated 33 patients with CAP-associated sepsis admitted to the emergency room and followed in the medical wards. Severity assessment scores (CURB-65, PSI, APACHE II, SOFA) and serologic markers (HMGB-1, RAGE, sRAGE) were evaluated on admission. RESULTS: Thirty patients with a diagnosis of CAP-associated sepsis were enrolled in the study within 24 hours after admission. Fourteen (46.6%) had pandemic (H1N1) influenza A virus, 2 (6.6%) had seasonal influenza A and 14 other diagnoses. Of the patients in the study group, 16 (53.3%) had a fatal outcome. ARDS was observed in 17 (56.6%) and a total of 22 patients had severe sepsis on admission (73%). The SOFA score showed the greatest difference between surviving and non-surviving groups (P = .003) with similar results in ARDS patients (P = .005). sRAGE levels tended to be higher in non-surviving (P = .058) and ARDS patients (P = .058). Logistic regression modeling demonstrated that SOFA (P = .013) and sRAGE (P = .05) were the only variables that modified the probability of a fatal outcome. CONCLUSION: The association of elevated sRAGE with a fatal outcome suggests that it may have an independent causal effect in CAP. SOFA scores were the only clinical factor with the ability to identify surviving and ARDS patients.

Sole infection by human metapneumovirus among children with radiographically diagnosed community-acquired pneumonia in a tropical region.

BACKGROUND: Limited information is available on the role of human metapneumovirus (HMPV) as the unique pathogen among children hospitalized for community-acquired pneumonia (CAP) in a tropical region. OBJECTIVE: We aimed to describe HMPV infection among children with CAP investigating bacterial and viral co-infections. PATIENTS AND METHODS: A prospective study was carried out in Salvador, North-East Brazil. Overall, 268 children aged <5 years hospitalized for CAP were enrolled. Human metapneumovirus RNA was detected in nasopharyngeal aspirates (NPA) by reverse transcription polymerase chain reaction. Sixteen other bacterial and viral pathogens were investigated by an expanded panel of laboratory methods. Chest X-ray taken on admission was read by an independent paediatric radiologist unaware of clinical information or the established aetiology. RESULTS: Human metapneumovirus RNA was detected in NPAs of 11 (4.1%) children, of which 4 (36%) had sole HMPV infection. The disease was significantly shorter among patients with sole HMPV infection in comparison with patients with mixed infection (4 ± 1 versus 7 ± 2 days, P = 0.03). Three of those four patients had alveolar infiltrates. CONCLUSION: Sole HMPV infection was detected in children with CAP in Salvador, North-East Brazil. HMPV may play a role in the childhood CAP burden.

Avaliação da adesão ao protocolo de pneumonia adquirida na comunidade na emergência do HCPA / Assessment of adherence to community acquired pneumonia protocol at HCPA emergency room

Objetivo: O estudo tem como objetivo principal avaliar o grau de adesão ao protocolo para manejo de Pneumonia Adquirida na Comunidade (PAC) vigente na emergência do Hospital de Clínicas de Porto Alegre (HCPA). Visamos também, buscar características epidemiológicas, clínicas e laboratoriais que possam contribuir para um desfecho mais grave nestes pacientes. Métodos: De forma prospectiva e observacional, selecionamos pacientes com diagnóstico clínico e radiológico de pneumonia, através de busca ativa na emergência do HCPA, durante o período de agosto a novembro de 2005. O já consagrado escore PORT (Pneumonia Patient outcomes Research Team) de gravidade foi utilizado para estratificação dos pacientes, os quais foram reavaliados no quinto dia. Resultados: Foram obtidos dados de 77 pacientes, com taxa geral de adesão de 65,8 por cento. Esta caiu para apenas 8,7 por cento quando analisados pacientes com PORT 1 e 2, subindo para 91,8 por cento quando considerados os pacientes com escores PORT maiores. Conclusões: Antibioticoterapia não recomendada, exames laboratoriais e internação desnecessários foram os pontos mais discordantes das recomendações do protocolo. Os dados demonstram a necessidade de uma maior adesão ao protocolo, com vistas à redução de gastos desnecessários e melhoria na qualidade do atendimento

Índice de gravedad en neumonía comunitaria hospitalizada / Severit predictiion index in hospitalized communitary acquired pneumonia

Fine's severity prediction index (SPI), was retrospectively analyzed in community acquired pneumonia (CAP), in patients at Concepción Regional Hospital, from June to August 2000. We studied 57 CAP patients: 23 as low risk and 34 as high risk patients. In comparison to low risk patients the main features of high risk patients were: older age (p < 0.00001), higher comorbility (p < 0.004), longer hospitalization (p < 0.0007) and higher mortality (p < 0.018). Mortality in low risk patients was similar to Fine's study: 4.3 versus 3.5%. In high risk patients mortality was 26% versus 38%. Main complications in our series were mechanical ventilation (43.8%), PaO2/FiO2 < 250 mmHg (43.8%), and hepatic coma (38.5%). As a conclusion, we recommend the use of SPI in CAP at Emergency Services in order to better evaluate mortality, optimizing criteria of hospital admission.

Se evaluó el Índice de Gravedad de Fine (IG) en neumonías de la comunidad (NAC) hospitalizadas en el Hospital Regional de Concepción en trabajo retrospectivo con 57 casos entre Junio y Agosto del año 2000. Se estudiaron 23 pacientes catalogados de bajo riesgo y 34 de alto riesgo. Características de alto riesgo fueron, mayor edad (p < 0,00001), mayor comorbilidad (p < 0,0004), estadía prolongada (p < 0,00007) y mayor mortalidad (p < 0,018). La mortalidad de bajo riesgo fue similar a la de Fine, 4,3% versus 3,5%, siendo menor en el grupo de alto riesgo, 26% versus 38%. Factores de mayor complicación en NAC fueron, ventilación mecánica (43,8%), PaO2/FiO2 < 250 mmHg (43,8%) y coma hepático (35,8%). Conclusión: es aconsejable el uso del IG en NAC a nivel de Servicios de Urgencia, para evaluar los riesgos de mortalidad, optimizando así los criterios de ingreso al hospital.

Clinical and molecular epidemiology of enterococcal bacteremia in a pediatric teaching hospital.

An apparent increase in the incidence of enterococcal bacteremias from 7 to 48/1000 bacteremias during 1986 to 1991 (p < 0.01) prompted this descriptive clinical and molecular epidemiologic study of 83 episodes occurring in 80 children between 1986 and 1992. Most community-acquired cases were in infants, in comparison with nosocomial episodes (24/26 and 34/57; p < 0.01); many of them were neonates (10/26 and 6/57; p < 0.01). Nosocomial cases were associated with underlying conditions including major surgery 56%, immunosuppression 49%, organ and tissue transplants 30%, and cardiac 32%, pulmonary 25%, renal 21%, and hepatic 21% disorders. Nosocomial episodes developed after a median of 32 days. There were 58 primary and 25 secondary bacteremias. Thirty-two episodes were polymicrobial and 44 organisms were involved. Twenty-six percent of the patients died. In 15%, death was preceded by septic shock, disseminated intravascular coagulation, and polymicrobial bacteremia (p < 0.01). Of 75 isolates, 82% were Enterococcus faecalis and 14% were Enterococcus faecium. Fourteen E. faecalis strains produced hemolysin; none produced beta-lactamase. Three had high-level resistance to gentamicin and 13 to streptomycin; two E. faecium and none of the E. faecalis strains were vancomycin resistant at a low level (p < 0.01) and one was ampicillin resistant. Pulsed-field gel electrophoresis of whole-cell DNA digested with restriction enzymes Sma I and Eag I showed five isolates with a homogeneous pattern, two with another homogeneous pattern, and 68 with distinct heterogeneous patterns. The increase in enterococcal bacteremias was not due to a clonal strain dissemination but to an increase in cases of heterogeneous enterococcal strains. We conclude that enterococcal septicemia is now an important cause of serious morbidity and death in critically ill children.