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1.
Eur J Clin Microbiol Infect Dis ; 38(7): 1255-1260, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30968258

RESUMO

Reduced target attainment of ß-lactam antibiotics is reported in critically ill patients. However, as target attainment of cefotaxime in severely ill pediatric sepsis patients may differ from adults due to age-related variation in pharmacokinetics, we aimed to assess target attainment of cefotaxime in this pilot study using meningococcal septic shock patients as a model for severe sepsis. Secondary analysis of prospectively collected data from a randomized controlled trial. Children with meningococcal septic shock (1 month to 18 years) included in this study received cefotaxime 100-150 mg/kg/day as antibiotic treatment. Left-over plasma samples were analyzed using LC-MS/MS to determine cefotaxime concentrations. MIC values from EUCAST were used to determine target attainment of cefotaxime for Neisseria meningitidis (0.125 mg/l), but also for Streptococcus pneumoniae (0.5 mg/l), Enterobacteriaceae (1 mg/l), and Staphylococcus aureus (4 mg/l). Target attainment was adequate when all samples exceeded MIC or fourfold MIC values. One thirty-six plasma samples of 37 severe septic shock patients were analyzed for cefotaxime concentrations. Median age was 2 years with a median PRISM-score of 24 and mortality of 24.8%. The median unbound cefotaxime concentration was 4.8 mg/l (range 0-48.7). Target attainment ranged from 94.6% for the MIC of N. meningitidis to 16.2% for fourfold the MIC S. aureus. Creatinine levels were significantly correlated with cefotaxime levels. Target attainment of cefotaxime with current dosing guidelines seems to be adequate for N. meningitidis but seems to fail for more frequently encountered pathogens in severely ill children.


Assuntos
Antibacterianos/farmacocinética , Cefotaxima/farmacocinética , Infecções Meningocócicas/tratamento farmacológico , Sepse/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Adolescente , Antibacterianos/sangue , Antibacterianos/uso terapêutico , Cefotaxima/sangue , Cefotaxima/uso terapêutico , Criança , Pré-Escolar , Estado Terminal , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Infecções Meningocócicas/sangue , Infecções Meningocócicas/complicações , Neisseria meningitidis/efeitos dos fármacos , Projetos Piloto , Sepse/microbiologia , Choque Séptico/microbiologia
2.
BMJ Case Rep ; 20182018 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-29507021

RESUMO

Acute epiglottitis is a severe and potentially life-threatening condition. Since the implementation of Haemophilus influenzae vaccination, the number of cases of epiglottitis has decreased and the proportion of other infectious causes has increased. We report a case of acute epiglottitis in a teenager caused by Neisseria meningitidis, an unusual pathogen.


Assuntos
Epiglotite/microbiologia , Infecções Meningocócicas/sangue , Infecções Meningocócicas/complicações , Neisseria meningitidis Sorogrupo W-135/isolamento & purificação , Doença Aguda , Administração Intravenosa , Adolescente , Antibacterianos/administração & dosagem , Ceftriaxona/administração & dosagem , Epiglotite/tratamento farmacológico , Humanos , Masculino , Infecções Meningocócicas/tratamento farmacológico , Reação em Cadeia da Polimerase
3.
Clin Infect Dis ; 67(5): 760-769, 2018 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-29509877

RESUMO

Background: The case fatality rate (CFR) from invasive meningococcal disease (IMD) in New York City (NYC) is greater than national figures, with higher rates among females than males across all age groups. Methods: We conducted a retrospective cohort study among 151 persons aged ≥15 years diagnosed with IMD in NYC during 2008-2016 identified through communicable disease surveillance. We examined demographic, clinical, and community-level associations with death to confirm the elevated risk of mortality among female IMD patients after adjusting for confounders and to determine factors associated with female IMD mortality. Relative risks of death were estimated using multivariable log-linear Poisson regression with a robust error variance. Results: Females had a higher CFR (n = 23/62; 37%) following IMD than males (n = 17/89; 19%) (adjusted relative risk [aRR], 2.1; 95% confidence interval [CI], 1.2-3.8). Controlling for demographic and clinical factors, there was a significant interaction between sex and fatal outcomes related to meningitis: the relative risk of death for females with meningitis was 13.7 (95% CI, 3.2-58.1) compared with males. In the model restricted to females, altered mental status (aRR, 7.5; 95% CI, 2.9-19.6) was significantly associated with an increased risk of death. Conclusions: Female mortality from IMD was significantly increased compared with males, controlling for other predictors of mortality. Sex-based differences in recognition and treatment need to be evaluated in cases of meningococcal disease. Our study highlights the importance of analyzing routine surveillance data to identify and address disparities in disease incidence and outcomes.


Assuntos
Monitoramento Epidemiológico , Infecções Meningocócicas/sangue , Infecções Meningocócicas/mortalidade , Fatores Sexuais , Adolescente , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Infecções Meningocócicas/complicações , Pessoa de Meia-Idade , Neisseria meningitidis/isolamento & purificação , Cidade de Nova Iorque/epidemiologia , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
4.
Pediatr Crit Care Med ; 19(6): e286-e291, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29432403

RESUMO

OBJECTIVES: Children with meningococcal sepsis are highly at risk for fulminant disease, multiple organ failure, and death. Recently, neutrophil extracellular traps levels have been indicated as a marker for severity in different kinds of sepsis. Our aim was to study the role of neutrophil extracellular traposis in meninogococcal sepsis in children. DESIGN: We measured myeloperoxidase-DNA, a marker for neutrophil extracellular traps, in serum of meningococcal sepsis patients upon admission to PICU, at 24 hours, and at 1 month and studied the association with clinical outcome. Subsequently, we tested whether Neisseria meningitidis, isolated from children with meningococcal sepsis, were able to induce neutrophil extracellular traposis, using confocal microscopy live imaging. SETTING: We used enzyme-linked immunosorbent assays to measure myeloperoxidase-DNA in patient serum. We also included inflammatory markers that were previously measured in this group. PATIENTS: We included exclusively children with meningococcal sepsis. INTERVENTIONS: From each patient, serum was collected for analysis. MEASUREMENTS AND MAIN RESULTS: Myeloperoxidase-DNA levels at admission (n = 35; median, 0.21 AU/mL; interquartile range, 0.12-0.27) and at 24 hours (n = 39; median, 0.14 AU/mL; interquartile range, 0.09-0.25) were significantly higher than the myeloperoxidase-DNA levels after 1 month (controls: n = 36; median, 0.07 AU/mL; interquartile range, 0.05-0.09; p < 0.001). We did not observe a correlation between myeloperoxidase-DNA levels and mortality, cell-free DNA, or other inflammatory markers. In addition, N. meningitidis are fast and strong inducers of neutrophil extracellular traposis. CONCLUSIONS: Children admitted to PICU for meningococcal sepsis have higher neutrophil extracellular traps levels at admission and after 24 hours than controls. Neutrophil extracellular traps levels were not associated with outcome, cell-free DNA, or other inflammatory markers. These neutrophil extracellular traps may be induced by N. meningitidis, since these are strong neutrophil extracellular traposis inducers.


Assuntos
Armadilhas Extracelulares/metabolismo , Infecções Meningocócicas/sangue , Neutrófilos/metabolismo , Sepse/sangue , Biomarcadores/sangue , Ácidos Nucleicos Livres/metabolismo , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Masculino , Peroxidase/metabolismo , Estudos Prospectivos
6.
J Infect Chemother ; 24(4): 305-308, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29233459

RESUMO

We present a 4-year-old girl who developed invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup C sequence type (ST)-4821. She was hospitalized due to fever, vomiting, rash and altered consciousness. Serogroup C N. meningitidis was isolated from blood culture taken on admission and was confirmed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry, a biochemical test, and molecular microbiological analysis. The patient was successfully treated with 50 mg/kg ceftriaxone every 12 hours for 7 days without any complications. The isolate was susceptible to a wide variety of ß-lactams and rifampin but was resistant to ciprofloxacin. The isolate harbored gyrA T91I and parC S87I mutations at the quinolone-resistance-determining regions. Multi-locus sequence typing revealed the isolates as ST-4821, which was identical to an endemic clone frequently detected in China. However, neither the patient nor her family members had traveled abroad. To our knowledge, this report is the first to describe an IMD patient caused by ciprofloxacin-resistant N. meningitidis ST-4821 in Japan, and is the first community-acquired IMD case due to this strain outside of China. The high proportion of ciprofloxacin resistance and hypervirulent features of this ST-4821 strain raise special public health concerns. We still consider ciprofloxacin is still appropriate drug for post-exposure chemoprophylaxis in Japan. However, nationwide surveillance for susceptibility of IMD isolates is necessary to establish the regional antibiogram, and thereby to avoid chemoprophylaxis failure.


Assuntos
Ciprofloxacino/efeitos adversos , Farmacorresistência Bacteriana , Infecções Meningocócicas/diagnóstico , Infecções Meningocócicas/microbiologia , Neisseria meningitidis/isolamento & purificação , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Ceftriaxona/administração & dosagem , Ceftriaxona/uso terapêutico , Pré-Escolar , Ciprofloxacino/uso terapêutico , Testes Diagnósticos de Rotina , Farmacorresistência Bacteriana/genética , Exantema , Feminino , Febre , Humanos , Infecções Meningocócicas/sangue , Infecções Meningocócicas/tratamento farmacológico , Mutação , Neisseria meningitidis/efeitos dos fármacos , Neisseria meningitidis/genética , Sorogrupo , Vômito
7.
Virulence ; 8(8): 1808-1819, 2017 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-29099305

RESUMO

Neisseria meningitidis is the causative agent of cerebrospinal meningitis and that of a rapidly progressing fatal septic shock known as purpura fulminans. Meningococcemia is characterized by bacterial adhesion to human endothelial cells of the microvessels. Host specificity has hampered studies on the role of blood vessels colonization in N. meningitidis associated pathogenesis. In this work, using a humanized model of SCID mice allowing the study of bacterial adhesion to human cells in an in vivo context we demonstrate that meningococcal colonization of human blood vessels is a prerequisite to the establishment of sepsis and lethality. To identify the molecular pathways involved in bacterial virulence, we performed transposon insertion site sequencing (Tn-seq) in vivo. Our results demonstrate that 36% of the genes that are important for growth in the blood of mice are dispensable when bacteria colonize human blood vessels, suggesting that human endothelial cells lining the blood vessels are feeding niches for N. meningitidis in vivo. Altogether, our work proposes a new paradigm for meningococcal virulence in which colonization of blood vessels is associated with metabolic adaptation and sustained bacteremia responsible for sepsis and subsequent lethality.


Assuntos
Bacteriemia/microbiologia , Infecções Meningocócicas/sangue , Infecções Meningocócicas/microbiologia , Microvasos/microbiologia , Neisseria meningitidis/fisiologia , Animais , Bacteriemia/sangue , Aderência Bacteriana , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos SCID , Neisseria meningitidis/genética
8.
Euro Surveill ; 22(28)2017 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-28749333

RESUMO

Between February and May 2017, two cases of invasive meningococcal disease caused by a new, rapidly expanding serogroup W meningococci variant were reported among students of an international university in Paris. Bacteriological investigations showed that isolates shared identical genotypic formula (W:P1.5,2:F1-1:cc11) and belonged to the South American/UK lineage. A vaccination campaign was organised that aimed at preventing new cases linked to potential persistence of the circulation of the bacteria in the students.


Assuntos
Infecções Meningocócicas/diagnóstico , Neisseria meningitidis Sorogrupo W-135/isolamento & purificação , Busca de Comunicante , Febre/etiologia , Genótipo , Humanos , Masculino , Infecções Meningocócicas/sangue , Infecções Meningocócicas/microbiologia , Tipagem Molecular , Neisseria meningitidis Sorogrupo W-135/genética , Paris , Sorogrupo , Estudantes , Sequenciamento Completo do Genoma , Adulto Jovem
9.
PLoS One ; 12(7): e0181508, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28742866

RESUMO

Factor H-binding protein (fHbp) is an important meningococcal vaccine antigen. Native outer membrane vesicles with over-expressed fHbp (NOMV OE fHbp) have been shown to induce antibodies with broader functional activity than recombinant fHbp (rfHbp). Improved understanding of this broad coverage would facilitate rational vaccine design. We performed a pair-wise analysis of 48 surface-exposed amino acids involved in interacting with factor H, among 383 fHbp variant group 1 sequences. We generated isogenic NOMV-producing meningococcal strains from an African serogroup W isolate, each over-expressing one of four fHbp variant group 1 sequences (ID 1, 5, 9, or 74), including those most common among invasive African meningococcal isolates. Mice were immunised with each NOMV, and sera tested for IgG levels against each of the rfHbp ID and for ability to kill a panel of heterologous meningococcal isolates. At the fH-binding site, ID pairs differed by a maximum of 13 (27%) amino acids. ID 9 shared an amino acid sequence common to 83 ID types. The selected ID types differed by up to 6 amino acids, in the fH-binding site. All NOMV and rfHbp induced high IgG levels against each rfHbp. Serum killing from mice immunised with rfHbp was generally less efficient and more restricted compared to NOMV, which induced antibodies that killed most meningococci tested, with decreased stringency for ID type differences. Breadth of killing was mostly due to anti-fHbp antibodies, with some restriction according to ID type sequence differences. Nevertheless, under our experimental conditions, no relationship between antibody cross-reactivity and variation fH-binding site sequence was identified. NOMV over-expressing different fHbp IDs belonging to variant group 1 induce antibodies with fine specificities against fHbp, and ability to kill broadly meningococci expressing heterologous fHbp IDs. The work reinforces that meningococcal NOMV with OE fHbp is a promising vaccine strategy, and provides a basis for rational selection of antigen sequence types for over-expression on NOMV.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Fator H do Complemento/imunologia , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Neisseria meningitidis/imunologia , Animais , Formação de Anticorpos , Antígenos de Bactérias/genética , Antígenos de Bactérias/uso terapêutico , Proteínas de Bactérias/genética , Proteínas de Bactérias/uso terapêutico , Clonagem Molecular , Feminino , Humanos , Imunização , Infecções Meningocócicas/sangue , Infecções Meningocócicas/imunologia , Vacinas Meningocócicas/genética , Vacinas Meningocócicas/uso terapêutico , Camundongos , Mutação , Neisseria meningitidis/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/uso terapêutico
11.
Ann Hematol ; 96(4): 589-596, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28124080

RESUMO

Eculizumab is indicated for the therapy of patients with symptomatic paroxysmal nocturnal hemoglobinuria (PNH). Due to inhibition of terminal complement cascade, patients on eculizumab are susceptible to Neisseria meningitidis infections. The two mainstays to reduce the risk of infection are vaccination and antibiotic prophylaxis. In this retrospective study, serologic response was analyzed after vaccination with a meningococcal vaccine in 23 PNH patients (median age 36 years; range 25 - 88 years; 15 males, 8 females) by measuring serum bactericidal assay (SBA) using rabbit complement (rSBA) titers against meningococcal serogroups A, C, W, and Y. Serologic protection was defined by an rSBA titer ≥1:8. Forty-three percent (10/23) were vaccinated more than once due to chronic eculizumab treatment. Overall serologic response for the meningococcal serogroups was A: 78% (18/23), C: 87% (20/23), W: 48% (11/23), and Y: 70% (16/23). No meningococcal infections have been observed. As immunological response to vaccines varies, the use of serologic response analyses is warranted. Re-vaccination with a tetravalent conjugate vaccine under eculizumab therapy every 3 years is essential or should be based on response rates. If meningococcal infection is suspected, standby therapy with ciprofloxacin and immediate medical evaluation are recommended. The novel vaccines covering serogroup B may even further reduce the risk for infection.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Hemoglobinúria Paroxística/sangue , Hemoglobinúria Paroxística/terapia , Vacinas Meningocócicas/administração & dosagem , Teste Bactericida do Soro/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos de Coortes , Esquema de Medicação , Feminino , Hemoglobinúria Paroxística/diagnóstico , Humanos , Masculino , Infecções Meningocócicas/sangue , Infecções Meningocócicas/diagnóstico , Infecções Meningocócicas/prevenção & controle , Pessoa de Meia-Idade , Coelhos , Estudos Retrospectivos , Testes Sorológicos/métodos , Resultado do Tratamento
12.
J Adolesc Health ; 59(2 Suppl): S21-8, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27449146

RESUMO

Meningococcal disease is a life-threatening infection that may progress rapidly, even after appropriate treatment has commenced. Early suspicion of the diagnosis is vital so that parenteral antibiotic treatment can be administered as soon as possible to reduce the complications of infection. The outcome of meningococcal disease is critically dependent on prompt recognition of two important complications: shock and raised intracranial pressure. Rapid recognition of disease and of these complications, together with appropriate management is crucial to the outcome of affected patients. This article summarizes the clinical features of invasive meningococcal disease, diagnostic tools, treatment modalities, and common post-infection sequelae.


Assuntos
Antibacterianos/uso terapêutico , Infecções Meningocócicas/diagnóstico , Infecções Meningocócicas/terapia , Neisseria meningitidis/imunologia , Diagnóstico Precoce , Tratamento de Emergência/métodos , Humanos , Infecções Meningocócicas/sangue , Infecções Meningocócicas/fisiopatologia , Tomografia Computadorizada por Raios X
13.
J Biol Chem ; 291(7): 3224-38, 2016 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-26655715

RESUMO

The degree of phosphorylation and phosphoethanolaminylation of lipid A on neisserial lipooligosaccharide (LOS), a major cell-surface antigen, can be correlated with inflammatory potential and the ability to induce immune tolerance in vitro. On the oligosaccharide of the LOS, the presence of phosphoethanolamine and sialic acid substituents can be correlated with in vitro serum resistance. In this study, we analyzed the structure of the LOS from 40 invasive isolates and 25 isolates from carriers of Neisseria meningitidis without disease. Invasive strains were classified as groups 1-3 that caused meningitis, septicemia without meningitis, and septicemia with meningitis, respectively. Intact LOS was analyzed by high resolution matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Prominent peaks for lipid A fragment ions with three phosphates and one phosphoethanolamine were detected in all LOS analyzed. LOS from groups 2 and 3 had less abundant ions for highly phosphorylated lipid A forms and induced less TNF-α in THP-1 monocytic cells compared with LOS from group 1. Lipid A from all invasive strains was hexaacylated, whereas lipid A of 6/25 carrier strains was pentaacylated. There were fewer O-acetyl groups and more phosphoethanolamine and sialic acid substitutions on the oligosaccharide from invasive compared with carrier isolates. Bioinformatic and genomic analysis of LOS biosynthetic genes indicated significant skewing to specific alleles, dependent on the disease outcome. Our results suggest that variable LOS structures have multifaceted effects on homeostatic innate immune responses that have critical impact on the pathophysiology of meningococcal infections.


Assuntos
Antígenos de Bactérias/toxicidade , Portador Sadio/microbiologia , Lipopolissacarídeos/toxicidade , Meningite Meningocócica/microbiologia , Infecções Meningocócicas/microbiologia , Neisseria meningitidis Sorogrupo B/patogenicidade , Neisseria meningitidis Sorogrupo C/patogenicidade , Acilação , Adolescente , Antígenos de Bactérias/biossíntese , Antígenos de Bactérias/química , Portador Sadio/sangue , Portador Sadio/líquido cefalorraquidiano , Portador Sadio/imunologia , Linhagem Celular Tumoral , Biologia Computacional , Perfilação da Expressão Gênica , Humanos , Imunidade Inata/efeitos dos fármacos , Lipopolissacarídeos/biossíntese , Lipopolissacarídeos/química , Meningite Meningocócica/sangue , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Meningocócica/imunologia , Infecções Meningocócicas/sangue , Infecções Meningocócicas/líquido cefalorraquidiano , Infecções Meningocócicas/imunologia , Estrutura Molecular , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Monócitos/metabolismo , Neisseria meningitidis Sorogrupo B/classificação , Neisseria meningitidis Sorogrupo B/imunologia , Neisseria meningitidis Sorogrupo B/metabolismo , Neisseria meningitidis Sorogrupo C/classificação , Neisseria meningitidis Sorogrupo C/imunologia , Neisseria meningitidis Sorogrupo C/metabolismo , Noruega , Fosforilação , Sepse/sangue , Sepse/líquido cefalorraquidiano , Sepse/imunologia , Sepse/microbiologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Fator de Necrose Tumoral alfa/metabolismo , Virulência
15.
Acta Med Port ; 28(3): 342-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26421787

RESUMO

INTRODUCTION: Meningococcal infection has a high mortality and morbidity. Recently a new prognostic scoring system was developed for paediatric invasive meningococcal disease, based on platelet count and base excess â base excess and platelets score. The main objective of this study was to evaluate the accuracy of base excess and platelets score to predict mortality in children admitted to intensive care due to invasive meningococcal disease. MATERIAL AND METHODS: Observational study, with retrospective data collection, during a 13.5 years period (01/2000 to 06/2013). Mortality by invasive meningococcal disease and related factors (organ dysfunction and multi-organ failure) were analysed. The base excess and platelets score was calculated retrospectively, to evaluate its accuracy in predicting mortality and compared with Paediatric Risk of Mortality and Paediatric Index of Mortality2. RESULTS: Were admitted 76 children with invasive meningococcal disease. The most frequent type of dysfunction was cardiovascular (92%), followed by hematologic (55%). Of the total, 47 patients (62%) had criteria for multi-organ failure. The global mortality was 16%. Neurologic and renal dysfunction showed the strongest association with mortality, adjusted odds ratio 315 (26 - 3 804) and 155 (20 - 1 299). After application of receiver operating characteristic curves, Base Excess and Platelets score had an area under curve of 0.81, Paediatric Index of Mortality2 of 0.91 and Paediatric Risk of Mortality of 0.96. DISCUSSION: The Base Excess and Platelets score showed good accuracy, although not as high as Paediatric Risk of Mortality or Paediatric Index of Mortality2. CONCLUSIONS: The Base Excess and Platelets score may be useful tool in invasive meningococcal disease because is highly sensitive and specific and is objectively measurable and readily available at presentation.


Assuntos
Desequilíbrio Ácido-Base/sangue , Infecções Meningocócicas/sangue , Infecções Meningocócicas/metabolismo , Contagem de Plaquetas , Desequilíbrio Ácido-Base/microbiologia , Pré-Escolar , Feminino , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Masculino , Infecções Meningocócicas/complicações , Infecções Meningocócicas/microbiologia , Portugal , Estudos Retrospectivos , Índice de Gravidade de Doença
16.
PLoS One ; 10(6): e0128993, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26053385

RESUMO

BACKGROUND: Despite vaccines and improved medical intensive care, clinicians must continue to be vigilant of possible Meningococcal Disease in children. The objective was to establish if the procalcitonin test was a cost-effective adjunct for prodromal Meningococcal Disease in children presenting at emergency department with fever without source. METHODS AND FINDINGS: Data to evaluate procalcitonin, C-reactive protein and white cell count tests as indicators of Meningococcal Disease were collected from six independent studies identified through a systematic literature search, applying PRISMA guidelines. The data included 881 children with fever without source in developed countries.The optimal cut-off value for the procalcitonin, C-reactive protein and white cell count tests, each as an indicator of Meningococcal Disease, was determined. Summary Receiver Operator Curve analysis determined the overall diagnostic performance of each test with 95% confidence intervals. A decision analytic model was designed to reflect realistic clinical pathways for a child presenting with fever without source by comparing two diagnostic strategies: standard testing using combined C-reactive protein and white cell count tests compared to standard testing plus procalcitonin test. The costs of each of the four diagnosis groups (true positive, false negative, true negative and false positive) were assessed from a National Health Service payer perspective. The procalcitonin test was more accurate (sensitivity=0.89, 95%CI=0.76-0.96; specificity=0.74, 95%CI=0.4-0.92) for early Meningococcal Disease compared to standard testing alone (sensitivity=0.47, 95%CI=0.32-0.62; specificity=0.8, 95% CI=0.64-0.9). Decision analytic model outcomes indicated that the incremental cost effectiveness ratio for the base case was £-8,137.25 (US $ -13,371.94) per correctly treated patient. CONCLUSIONS: Procalcitonin plus standard recommended tests, improved the discriminatory ability for fatal Meningococcal Disease and was more cost-effective; it was also a superior biomarker in infants. Further research is recommended for point-of-care procalcitonin testing and Markov modelling to incorporate cost per QALY with a life-time model.


Assuntos
Calcitonina/sangue , Calcitonina/economia , Análise Custo-Benefício , Infecções Meningocócicas/sangue , Infecções Meningocócicas/diagnóstico , Precursores de Proteínas/sangue , Precursores de Proteínas/economia , Proteína C-Reativa/metabolismo , Peptídeo Relacionado com Gene de Calcitonina , Procedimentos Clínicos , Árvores de Decisões , Humanos , Contagem de Leucócitos , Curva ROC
17.
Lancet Infect Dis ; 15(5): 552-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25728843

RESUMO

BACKGROUND: Diagnosis of meningococcal disease relies on recognition of clinical signs and symptoms that are notoriously non-specific, variable, and often absent in the early stages of the disease. Loop-mediated isothermal amplification (LAMP) has previously been shown to be fast and effective for the molecular detection of meningococcal DNA in clinical specimens. We aimed to assess the diagnostic accuracy of meningococcal LAMP as a near-patient test in the emergency department. METHODS: For this observational cohort study of diagnostic accuracy, children aged 0-13 years presenting to the emergency department of the Royal Belfast Hospital for Sick Children (Belfast, UK) with suspected meningococcal disease were eligible for inclusion. Patients underwent a standard meningococcal pack of investigations testing for meningococcal disease. Respiratory (nasopharyngeal swab) and blood specimens were collected from patients and tested with near-patient meningococcal LAMP and the results were compared with those obtained by reference laboratory tests (culture and PCR of blood and cerebrospinal fluid). FINDINGS: Between Nov 1, 2009, and Jan 31, 2012, 161 eligible children presenting at the hospital underwent the meningococcal pack of investigations and were tested for meningococcal disease, of whom 148 consented and were enrolled in the study. Combined testing of respiratory and blood specimens with use of LAMP was accurate (sensitivity 89% [95% CI 72-96], specificity 100% [97-100], positive predictive value 100% [85-100]; negative predictive value 98% [93-99]) and diagnostically useful (positive likelihood ratio 213 [95% CI 13-infinity] and negative likelihood ratio 0·11 [0·04-0·32]). The median time required for near-patient testing from sample to result was 1 h 26 min (IQR 1 h 20 min-1 h 32 min). INTERPRETATION: Meningococcal LAMP is straightforward enough for use in any hospital with basic laboratory facilities, and near-patient testing with this method is both feasible and effective. By contrast with existing UK National Institute of Health and Care Excellence guidelines, we showed that molecular testing of non-invasive respiratory specimens from children is diagnostically accurate and clinically useful. FUNDING: Health and Social Care Research and Development, Public Health Agency, Northern Ireland.


Assuntos
DNA Bacteriano/genética , Infecções Meningocócicas/diagnóstico , Neisseria meningitidis/genética , Técnicas de Amplificação de Ácido Nucleico/normas , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , DNA Bacteriano/isolamento & purificação , Serviço Hospitalar de Emergência , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Infecções Meningocócicas/sangue , Infecções Meningocócicas/líquido cefalorraquidiano , Infecções Meningocócicas/microbiologia , Nasofaringe/microbiologia , Neisseria meningitidis/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico/métodos , Guias de Prática Clínica como Assunto , Sensibilidade e Especificidade , Reino Unido
19.
Epidemiol Infect ; 143(11): 2440-5, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25483268

RESUMO

Paediatricians recognize that using the time-dependent community-acquired vs. hospital-acquired bloodstream infection (BSI) dichotomy to guide empirical treatment no longer distinguishes between causative pathogens due to the emergence of healthcare-associated BSIs. However, paediatric epidemiological evidence of the aetiology of BSIs in relation to hospital admission in England is lacking. For 12 common BSI-causing pathogens in England, timing of laboratory reports of positive paediatric (3 months to 5 years) bacterial blood isolates were linked to in-patient hospital data and plotted in relation to hospital admission. The majority (88·6%) of linked pathogens were isolated <2 days after hospital admission, including pathogens widely regarded as hospital acquired: Enterococcus spp. (67·2%) and Klebsiella spp. (88·9%). Neisseria meningitidis, Streptococcus pneumoniae, group A streptococcus and Salmonella spp. were unlikely to cause hospital-acquired BSI. Pathogens commonly associated with hospital-acquired BSI are being isolated <2 days after hospital admission alongside pathogens commonly associated with community-acquired BSI. We confirm that timing of blood samples alone does not differentiate between bacterial pathogens. Additional factors including clinical patient characteristics and healthcare contact should be considered to help predict the causative pathogen and guide empirical antibiotic therapy.


Assuntos
Bacteriemia/sangue , Infecção Hospitalar/sangue , Infecções por Klebsiella/sangue , Infecções Meningocócicas/sangue , Infecções Pneumocócicas/sangue , Infecções por Salmonella/sangue , Bacteriemia/diagnóstico , Pré-Escolar , Estudos de Coortes , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/diagnóstico , Infecção Hospitalar/diagnóstico , Coleta de Dados , Diagnóstico Diferencial , Inglaterra , Enterococcus/isolamento & purificação , Feminino , Infecções por Bactérias Gram-Positivas/sangue , Infecções por Bactérias Gram-Positivas/diagnóstico , Humanos , Lactente , Klebsiella/isolamento & purificação , Infecções por Klebsiella/diagnóstico , Masculino , Infecções Meningocócicas/diagnóstico , Neisseria meningitidis/isolamento & purificação , Infecções Pneumocócicas/diagnóstico , Estudos Retrospectivos , Salmonella/isolamento & purificação , Infecções por Salmonella/diagnóstico , Infecções Estreptocócicas/sangue , Infecções Estreptocócicas/diagnóstico , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pyogenes/isolamento & purificação , Fatores de Tempo
20.
Rev Med Chir Soc Med Nat Iasi ; 118(2): 497-502, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25076721

RESUMO

AIM: To assess the influence of preadmission antibiotic therapy on the results of the classical methods for bacteriological confirmation of meningococcal disease (MD). MATERIAL AND METHODS: Retrospective study of the MD cases diagnosed in the "St. Parascheva" Universitary Clinical Infectious Diseases Iasi between 1994 and 2011. RESULTS: The etiological diagnosis was made by identifying the meningococcus in the CSF (cerebrospinal fluid) in 71.9% of the 323 patients and by blood culture in 8%. Preadmission antibiotic therapy received 39% of the patients, thus the sensitivity of test was significantly reduced: direct examination from 64.6% to 43.2% (p < 0.001), cultures from 55.9% to 27.2% (p < 0.001), and latex-agglutination from 84.6% to 58.8% (p = 0.003). The rate of positive CSF decreased from 82.1% to 56% (p < 0.001). Preadmission antibiotic therapy significantly increased the ratio of cases in which meningococcus was not detected in CSF by any of the classical methods (44% compared to 17.9% in the cases without prior treatment). The proportion of cases in which meningococcal isolation was done by two methods decreased from 38.5% to 19.2%, and of those by all three methods from 16.9% to 5.6% (p < 0.001). Preadmission antibiotic therapy also decreased the rate of positive blood cultures from 14.7% to 3.5% (Fisher's exact test, p = 0.009). CONCLUSIONS: Antibiotic treatment prior to admission significantly decreases the percentage of patients with MD in which meningococcal isolation can be done; this requires the use of a more sensitive diagnosis method (ex. qPCR).


Assuntos
Antibacterianos/administração & dosagem , Líquido Cefalorraquidiano/microbiologia , Infecções Meningocócicas/diagnóstico , Neisseria meningitidis/isolamento & purificação , Admissão do Paciente , Soro/microbiologia , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Hospitais de Isolamento , Hospitais Universitários , Humanos , Testes de Fixação do Látex/métodos , Infecções Meningocócicas/sangue , Infecções Meningocócicas/líquido cefalorraquidiano , Infecções Meningocócicas/microbiologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade
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