RESUMO
BACKGROUND: Solid organ transplant (SOT) recipients are at risk of infections of the central nervous system. However, the incidence and clinical course of bacterial meningitis in SOT recipients are unclear. We studied occurrence, disease course, and prognosis of bacterial meningitis in SOT recipients in the Netherlands. METHODS: All patients with a medical history of solid organ transplantation were selected from our nationwide prospective cohort study on community-acquired bacterial meningitis in patients >16 years old, performed from March 1, 2006 to October 31, 2014. Data on patient history, symptoms and signs on admission, treatment, and outcome were collected prospectively. For transplant recipients, additional information was collected retrospectively. RESULTS: We identified 6 SOT recipients, all receiving renal transplants. The annual incidence of bacterial meningitis was 7-fold higher (95% confidence interval [CI] 2.94-17.02, P < 0.001) for renal transplant recipients as compared with the general population (9.56 [95% CI 3.98-22.96] vs. 1.35 [95% CI 1.28-1.43] per 100,000 patients per year). One of the 6 patients (17%) presented with the classic presentation of bacterial meningitis (fever, neck stiffness, and change in mental status). Seizures were common, occurring in 33% of patients. Streptococcus pneumoniae and Listeria monocytogenes were identified in 2 patients each, and Escherichia coli and Pseudomonas aeruginosa were both identified once. Four of 6 patients (67%) had an unfavorable functional outcome. CONCLUSION: Bacterial meningitis is a rare but devastating complication of solid organ transplantation. SOT recipients are at high risk for developing meningitis, and recognition of this condition may be difficult, owing to atypical clinical manifestation.
Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Transplante de Rim/efeitos adversos , Meningites Bacterianas/epidemiologia , Transplantados/estatística & dados numéricos , Adulto , Idoso , Infecções Comunitárias Adquiridas/complicações , Infecções Comunitárias Adquiridas/etiologia , Infecções Comunitárias Adquiridas/microbiologia , Escherichia coli/isolamento & purificação , Feminino , Humanos , Incidência , Listeria monocytogenes/isolamento & purificação , Masculino , Meningites Bacterianas/complicações , Meningites Bacterianas/etiologia , Meningites Bacterianas/microbiologia , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prognóstico , Estudos Prospectivos , Pseudomonas aeruginosa/isolamento & purificação , Estudos Retrospectivos , Fatores de Risco , Streptococcus pneumoniae/isolamento & purificaçãoRESUMO
BACKGROUND: The diagnosis of meningitis in non-surgical hospitalized patients is often difficult and diagnostic accuracy of clinical, laboratory, and radiological characteristics is unknown. AIM: To assess diagnostic accuracy for individual clinical characteristics of patients suspected of non-surgical nosocomial central nervous system (CNS) infections. METHODS: In a prospective multi-centre cohort study in the Netherlands with adults suspected of CNS infections, consecutive patients who underwent a lumbar puncture for the suspicion of a non-surgical nosocomial CNS infection were included. All episodes were categorized into five final clinical diagnosis categories, as reference standard: CNS infection, CNS inflammatory disease, systemic infection, other neurological disease, or non-systemic, non-neurological disease. FINDINGS: Between 2012 and 2022, 114 out of 1275 (9%) patients included in the cohort had suspected non-surgical nosocomial CNS infection: 16 (14%) had a confirmed diagnosis, including four (25%) with bacterial meningitis, nine (56%) with viral CNS infections, two (13%) fungal meningitis, and one (6%) parasitic meningitis. Diagnostic accuracy of individual clinical characteristics was generally low. Elevated CSF leucocyte count had the highest sensitivity (81%; 95% confidence interval (CI): 54-96) and negative predictive value (NPV) (96%; 95% CI: 90-99). When combining the presence of abnormalities in neurological or CSF examination, sensitivity for diagnosing a CNS infection was 100% (95% CI: 79-100) and NPV 100% (95% CI: 78-100). CSF examination changed clinical management in 47% of patients. CONCLUSION: Diagnostic accuracy for individual clinical characteristics was low, with elevated CSF leucocyte count having the highest sensitivity and NPV.
Assuntos
Infecções do Sistema Nervoso Central , Infecção Hospitalar , Meningites Bacterianas , Adulto , Humanos , Estudos de Coortes , Estudos Prospectivos , Infecção Hospitalar/diagnóstico , Infecções do Sistema Nervoso Central/diagnóstico , Infecções do Sistema Nervoso Central/microbiologia , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/microbiologiaRESUMO
Bacterial meningitis is a severe disease which affects 35.000 Europeans each year and has a mortality rate of about 20%. During the past 25 years the epidemiology of bacterial meningitis has changed significantly due to the implementation of vaccination against Haemophilus influenzae, Neisseria meningtidis group C and Streptococcus pneumoniae. Due to these vaccines, meningitis is now predominantly a disease occurring in adults, caused especially by Streptococcus pneumoniae, while it was formerly a child disease which was largely caused by Haemophilus influenzae. Bacterial meningitis is often difficult to recognize since the classical presentation with neck stiffness, reduced awareness and fever occurs in less than half of the patients. The only way to diagnose or exclude bacterial meningitis is by performing low-threshold cerebrospinal fluid examination with a suspicion of bacterial meningitis. The treatment consists of the prescription of antibiotics and dexamethasone.
Assuntos
Vacinas Bacterianas , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/prevenção & controle , Diagnóstico Diferencial , Febre/etiologia , Haemophilus influenzae/isolamento & purificação , Humanos , Meningites Bacterianas/epidemiologia , Meningites Bacterianas/microbiologia , Neisseria meningitidis/isolamento & purificação , Fatores de Risco , Punção Espinal , Streptococcus pneumoniae/isolamento & purificaçãoRESUMO
OBJECTIVES: Confirming the diagnosis in viral central nervous system (CNS) infections can be difficult with the currently available diagnostic tools. Virus discovery cDNA-amplified fragment length polymorphism next-generation sequencing (VIDISCA-NGS) is a promising viral metagenomic technique that enables the detection of all viruses in a single assay. We performed a retrospective study on the diagnostic accuracy of VIDISCA-NGS in cerebrospinal fluid (CSF) of individuals with suspected CNS infections. METHODS: Consecutive adult patients presenting to the Emergency Department or inpatients, who underwent a lumbar puncture for the suspicion of a CNS infection, were included if they were diagnosed with a viral CNS infection, or if a viral CNS infection was initially suspected but eventually a different diagnosis was made. A quantitative PCR panel of the most common causative viruses was performed on CSF of these patients as reference standard and compared with the results of VIDISCA-NGS, the index test. RESULTS: We included 38 individuals with viral CNS infections and 35 presenting with suspected CNS infection for whom an alternative aetiology was finally established. Overall sensitivity and specificity were 52% (95% CI 31%-73%) and 100% (95% CI 91%-100%), respectively. One enterovirus, detected by VIDISCA-NGS, was only identified by quantitative PCR upon retesting. Additional viruses identified by VIDISCA-NGS consisted of GB virus C, human papillomavirus, human mastadenovirus C, Merkel cell polyoma virus and anelloviruses. CONCLUSION: In patients for whom routine diagnostics do not yield a causative pathogen, VIDISCA-NGS can be of additional value as it can detect a broader range of viruses, but it does not perform well enough to replace quantitativePCR.
Assuntos
Análise do Polimorfismo de Comprimento de Fragmentos Amplificados/métodos , Infecções do Sistema Nervoso Central/diagnóstico , Infecções do Sistema Nervoso Central/virologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Viroses/diagnóstico , Vírus/isolamento & purificação , Adulto , Idoso , DNA Viral/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Viroses/líquido cefalorraquidianoRESUMO
BACKGROUND AND PURPOSE: There are concerns that the coronavirus disease 2019 (COVID-19) outbreak negatively affects the quality of care for acute cardiovascular conditions. We assessed the impact of the COVID-19 outbreak on trends in hospital admissions and workflow parameters of acute stroke care in Amsterdam, The Netherlands. METHODS: We used data from the three hospitals that provide acute stroke care for the Amsterdam region. We compared two 7-week periods: one during the peak of the COVID-19 outbreak (March 16th-May 3th 2020) and one prior to the outbreak (October 21st-December 8th 2019). We included consecutive patients who presented to the emergency departments with a suspected stroke and assessed the change in number of patients as an incidence-rate ratio (IRR) using a Poisson regression analysis. Other outcomes were the IRR for stroke subtypes, change in use of reperfusion therapy, treatment times, and in-hospital complications. RESULTS: During the COVID-19 period, 309 patients presented with a suspected stroke compared to 407 patients in the pre-COVID-19 period (IRR 0.76 95%CI 0.65-0.88). The proportion of men was higher during the COVID-19 period (59% vs. 47%, p < 0.001). There was no change in the proportion of stroke patients treated with intravenous thrombolysis (28% vs. 30%, p = 0.58) or endovascular thrombectomy (11% vs 12%, p = 0.82) or associated treatment times. Seven patients (all ischemic strokes) were diagnosed with COVID-19. CONCLUSION: We observed a 24% decrease in suspected stroke presentations during the COVID-19 outbreak, but no evidence for a decrease in quality of acute stroke care.
Assuntos
COVID-19 , Pandemias , Acidente Vascular Cerebral/terapia , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Serviços Médicos de Emergência , Feminino , Hospitalização , Humanos , Incidência , AVC Isquêmico/complicações , AVC Isquêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Distribuição de Poisson , Qualidade da Assistência à Saúde , Reperfusão , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Trombectomia/estatística & dados numéricos , Terapia Trombolítica/estatística & dados numéricos , Tempo para o Tratamento , Resultado do TratamentoRESUMO
BACKGROUND: Streptococcus pneumoniae is the most common pathogen causing bacterial meningitis. The routine use of multivalent conjugate pneumococcal vaccines has led to a decline of invasive pneumococcal disease caused by serotypes included in the vaccine serotypes. Recently, several reports have described a concomitant rise in the incidence of non-vaccine serotypes, suggesting serotype replacement. OBJECTIVE: We aim to review the effect of pneumococcal vaccination on the incidence of pneumococcal meningitis in Europe and northern America with a particular interest in serotype replacement. SOURCES: Articles that include data on invasive pneumococcal disease incidence before and after the introduction of vaccination, or on invasive pneumococcal serotype, are discussed, with a focus on pneumococcal meningitis. CONTENT: The introduction of pneumococcal conjugate vaccines has universally resulted in a decline in vaccine-serotype pneumococcal meningitis incidence throughout Europe and northern America. Serotype replacement by non-vaccine serotypes has however been reported following the introduction of the 7-, 10- and 13-valent pneumococcal conjugate vaccines, which in several regions abolished the overall effect of vaccination on pneumococcal meningitis incidence. IMPLICATIONS: The promising decline in the incidence of pneumococcal meningitis following the introduction of vaccination seems to have been temporary. Replacement by non-vaccine serotypes illustrates that pneumococcal meningitis continues to pose a major challenge. We need new approaches to prevention, new vaccines and continued efforts to improve treatment for patients with pneumococcal meningitis.
Assuntos
Meningite Pneumocócica/epidemiologia , Infecções Pneumocócicas/epidemiologia , Vacinas Pneumocócicas/imunologia , Europa (Continente)/epidemiologia , Vacina Pneumocócica Conjugada Heptavalente/imunologia , Humanos , Incidência , Meningite Pneumocócica/prevenção & controle , América do Norte/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Sorogrupo , Streptococcus pneumoniae/imunologia , Vacinação , Vacinas ConjugadasRESUMO
OBJECTIVES: To examine the incidence and mortality of brain abscesses. METHODS: We accessed nationwide population-based medical registries to obtain data for patients with first-time brain abscesses in Denmark from 1982 through 2016. Annual age- and sex-standardized incidence rates with 95% confidence intervals were calculated and compared by direct standardization. We used Cox regression to compute mortality rate ratios adjusted for age and year groups, sex and Charlson comorbidity index score. RESULTS: We identified 1384 patients (37% female). The overall standardized incidence rate of brain abscess was 0.76 per 100â¯000 person-years (95% confidence interval 0.70-0.81). The incidence rates gradually increased from 0.60 during 1982-88 to 0.90 per 100â¯000 person-years during 2010-16, yielding an incidence rate ratio of 1.50 (95% confidence interval 1.26-1.79). This increase in incidence was most pronounced in the proportions of brain abscess patients >40 years of age and those with immuno-compromise. The 1-year mortality declined from 29% during 1982-88 to 20% during 2010-16, yielding an adjusted mortality rate ratio of 0.44 (95% confidence interval 0.31-0.63). Risk factors for death were advanced age, Charlson comorbidity index >0, immuno-compromised status and congenital heart disease. CONCLUSIONS: The incidence of brain abscess in Denmark is low but increasing, especially in the elderly, along with an increasing proportion of brain abscess patients with immuno-compromise. The prognosis has improved during the last decades, but mortality remains high. Risk factors for death in our study were advanced age, presence of comorbidity, immuno-compromised status and congenital heart disease.
Assuntos
Abscesso Encefálico/mortalidade , Sistema de Registros , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Comorbidade , Dinamarca/epidemiologia , Feminino , Cardiopatias/congênito , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Sexuais , Adulto JovemRESUMO
OBJECTIVES: To perform a cross-sectional cohort study on long-term neurologic, cognitive and quality-of-life outcome in adults surviving pneumococcal meningitis. METHODS: Adult survivors of community-acquired pneumococcal meningitis from a Dutch nationwide prospective cohort study were evaluated 1 to 5 years after acute illness. The control group consisted of partners or proxies of patients. Neurologic examination was performed and cognitive domains were tested with the Vienna Test System Cognitive Basic Assessment Test set (VTS COGBAT). The Research and Development (RAND)-36 and adapted Cognitive and Emotional Consequences of Stroke (CLCE)-24 questionnaires assessed perceived cognitive functioning and quality of life. Differences between group scores were tested with multivariate analyses of variance. RESULTS: A total of 80 pneumococcal meningitis patients and 69 controls were evaluated. After a median of 2 years (interquartile range, 2-3) after acute illness, 27 (34%) of 79 patients had persistent neurologic sequelae, most commonly hearing loss (21/79, 27%). On overall neuropsychologic evaluation, patients performed worse than the controls (MANCOVA; p 0.008), with alertness (z score -0.33, p 0.011) and cognitive flexibility (z score -0.33, p 0.027) as the most affected domains. Cognitive impairment was present in 11 (14%) of 79 patients. CLCE-24 questionnaires revealed cognitive impairment on all domains, most commonly for cognitive speed (53/75, 71%), attention (45/75, 60%) and memory (46/75, 61%). Patients had lower quality-of-life scores than controls (item physical functioning, (median) patients vs. controls, 80 vs. 95, p < 0.001; social functioning, (median) 81 vs. 100, p 0.003; perceived health, (mean) 59 vs. 70, p 0.005), which correlated with cognitive complaints (R = 0.66, p < 0.001). CONCLUSIONS: Adults after pneumococcal meningitis are at high risk of long-term neurologic and neuropsychologic deficits impairing daily life activities and quality of life.
Assuntos
Atividades Cotidianas/psicologia , Cognição/fisiologia , Disfunção Cognitiva/patologia , Meningite Pneumocócica/tratamento farmacológico , Qualidade de Vida/psicologia , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Meningite Pneumocócica/psicologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Pneumonia is considered a focus of infection in patients presenting with community-acquired bacterial meningitis but the impact on disease course is unclear. The aim was to study presenting characteristics, clinical course and outcome of meningitis patients with co-existing pneumonia on admission. METHODS: We evaluated adult patients with community-acquired bacterial meningitis with pneumonia on admission in a nationwide, prospective cohort performed from March 2006 to June 2017. We performed logistic regression analysis to identify clinical characteristics predictive of pneumonia on admission, and to quantify the effect of pneumonia on outcome. RESULTS: Pneumonia was diagnosed on admission in 315 of 1852 (17%) bacterial meningitis episodes and confirmed by chest X-ray in 256 of 308 (83%) episodes. Streptococcus pneumoniae was the causative organism in 256 of 315 episodes (81%). Pneumonia on admission was associated with advanced age (OR 1.03 per year increase, 95% CI 1.02-1.04, p < 0.001), alcoholism (OR 1.96, 95% CI 1.23-3.14, p 0.004), cancer (OR 1.54, 95% CI 1.12-2.13, p 0.008), absence of otitis or sinusitis (OR 0.44, 95% CI 0.32-0.59, p < 0.001) and S. pneumoniae (OR 2.14, 95% CI 1.55-2.95, p < 0.001) in the multivariate analysis. An unfavourable outcome defined as a score of 1-4 on the Glasgow Outcome Scale was observed in 172 (55%) episodes and 87 patients (28%) died. Pneumonia on admission was independently associated with unfavourable outcome and mortality in the multivariate analysis (OR 1.48, 95% CI 1.12-1.96; p 0.005). CONCLUSION: Pneumonia on admission in bacterial meningitis is a frequent coexisting infection and is independently associated with unfavourable outcome and mortality.
Assuntos
Infecções Comunitárias Adquiridas/microbiologia , Meningites Bacterianas/complicações , Pneumonia/microbiologia , Idoso , Antibacterianos/uso terapêutico , Feminino , Humanos , Modelos Logísticos , Masculino , Meningites Bacterianas/líquido cefalorraquidiano , Meningites Bacterianas/tratamento farmacológico , Pessoa de Meia-Idade , Países Baixos , Pneumonia/diagnóstico por imagem , Estudos Prospectivos , Radiografia , Fatores de RiscoRESUMO
OBJECTIVE: To study whether genetic variation in coagulation and fibrinolysis genes contributes to cerebrovascular complications in bacterial meningitis. METHODS: We performed a nationwide prospective genetic association study in adult community-acquired bacterial meningitis patients. The exons and flanking regions of 16 candidate genes involved in coagulation and fibrinolysis pathways were sequenced. We analyzed whether genetic variation in these genes resulted in a higher risk of cerebrovascular complications, unfavorable outcome and differences in thrombocyte count on admission. RESULTS: From 2006 to 2011, a total of 1101 bacterial meningitis patients were identified of whom 622 supplied DNA for genotyping and passed genetic quality control steps. In 139 patients (22%) the episode of bacterial meningitis was complicated by cerebral infarction, and 188 (30%) had an unfavorable outcome. We identified the functional variant rs494860 in the protein Z (PROZ) gene as our strongest association with occurrence of cerebral infarction (odds ratio (OR) 0.49 (95% confidence interval 0.33-0.73), pâ¯=â¯5.2â¯×â¯10-4). After Bonferroni correction for multiple testing no genetic variant was significantly associated (p-value threshold 2.7â¯×â¯10-4). CONCLUSION: Our study suggests a functional genetic variation in the PROZ gene, rs494860, may be of importance in bacterial meningitis pathogenesis and cerebral infarction risk. Replication of this finding in other cohort studies populations is needed.
Assuntos
Coagulação Sanguínea/genética , Transtornos Cerebrovasculares/etiologia , Fibrinólise/genética , Estudos de Associação Genética , Meningites Bacterianas/complicações , Meningite Pneumocócica/complicações , Adulto , Idoso , Infarto Cerebral/epidemiologia , Infarto Cerebral/etiologia , Transtornos Cerebrovasculares/microbiologia , Estudos de Coortes , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Variação Genética , Humanos , Masculino , Meningites Bacterianas/epidemiologia , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Razão de Chances , Estudos Prospectivos , Análise de Sequência de DNARESUMO
BACKGROUND: Hyponatraemia in adults with bacterial meningitis has been described as a common complication, but its true prevalence and clinical importance are unknown. AIM: To investigate the prevalence, clinical characteristics and consequences of hyponatraemia in bacterial meningitis in adults. DESIGN: Nationwide observational cohort study. METHODS: We prospectively assessed the prevalence and clinical characteristics of hyponatraemia among 696 adults with community-acquired bacterial meningitis. Symptoms and signs on admission, blood and CSF test results, radiological examinations and complications during admission were recorded. RESULTS: Sodium levels were determined at admission in 685/696 episodes of bacterial meningitis (98%). Hyponatraemia (<135 mmol/l) was seen in 208/685 (30%) and was classified as severe (<130 mmol/l) in 38 (6%). Hyponatraemia developed during admission in an additional 53 episodes. Hyponatraemia was not associated with an increase in symptoms, with complications or with unfavourable outcome. Treatment for hyponatraemia was initiated in 16% of episodes, but did not influence its duration. DISCUSSION: Hyponatraemia appears both common and benign in adults with bacterial meningitis. In cases of severe hyponatraemia, we suggest the use of fluid maintenance therapy.
Assuntos
Hiponatremia/epidemiologia , Meningites Bacterianas/complicações , Adulto , Estudos de Coortes , Infecções Comunitárias Adquiridas/complicações , Humanos , Listeria monocytogenes/isolamento & purificação , Neisseria meningitidis/isolamento & purificação , Países Baixos/epidemiologia , Prevalência , Fatores de Risco , Streptococcus pneumoniae/isolamento & purificaçãoRESUMO
Haemophilus influenzae is an uncommon cause of bacterial meningitis in adults. This report describes a prospective evaluation of 16 episodes of community-acquired H. influenzae meningitis in a nationwide study on bacterial meningitis. Predisposing conditions were present in eight (50%) of the 16 episodes; the most common predisposing conditions were otitis or sinusitis (five episodes; 31%) and remote neurosurgery or head trauma (three episodes; 19%). One (6%) episode was fatal and hearing loss occurred in four (25%) episodes. It was concluded that H. influenzae meningitis in adults is a disease with a rather benign clinical course and a relatively good prognosis compared with pneumococcal meningitis.
Assuntos
Infecções Comunitárias Adquiridas/microbiologia , Haemophilus influenzae/classificação , Meningite por Haemophilus/microbiologia , Adulto , Infecções Comunitárias Adquiridas/líquido cefalorraquidiano , Infecções Comunitárias Adquiridas/complicações , Feminino , Perda Auditiva/etiologia , Humanos , Masculino , Meningite por Haemophilus/líquido cefalorraquidiano , Meningite por Haemophilus/complicações , Pessoa de Meia-Idade , Estudos Prospectivos , SorotipagemRESUMO
Bacterial infections of the central nervous system present as a medical emergency, thus requiring rapid diagnosis and immediate treatment. The most prevalent bacterial infections seen in the intensive care unit can be summarized as acute bacterial meningitis, subdural empyema, intracerebral abscess, and ventriculitis, which all commonly involve the brain parenchyma. The infections can either be community-acquired or hospital-acquired, e.g., after neurosurgical intervention, as a complication of severe neurotrauma or related to indwelling cerebrospinal fluid drains. Community-acquired bacterial meningitis is most commonly caused by the pneumococcus (Streptococcus pneumoniae) and meningococcus (Neisseria meningtidis), and is often complicated by hearing loss, cerebrovascular complications, and seizures. Brain abscesses are frequently associated with contiguous or metastatic foci of infection such as otitis, sinusitis, pneumonia, or endocarditis which need to be detected and treated early during disease course. Despite optimal treatment, many patients are at risk for both major systemic and neurologic complications, leading to a substantial mortality and risk of major disability in survivors. Empiric treatment depends on regional antibiotic resistance patterns of common pathogens. For subdural empyema and brain abscesses, neurosurgical drainage of the infection is required alongside prolonged antibiotic treatment.
Assuntos
Infecções Bacterianas do Sistema Nervoso Central/terapia , Infecções Bacterianas do Sistema Nervoso Central/microbiologia , HumanosRESUMO
BACKGROUND: The existing heterogeneity in diagnostic work-up and treatment strategies in bacterial meningitis was the incentive to develop a European evidence-based guideline, which was published in 2016 by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group on Infections of the Brain (ESGIB). AIMS: To summarize salient features of the guideline, identify recent developments and challenges currently faced. SOURCES: The ESCMID guideline, ongoing trial registries. CONTENT: Epidemiology, clinical symptoms, diagnostic work-up and therapy strategies of acute bacterial meningitis. IMPLICATIONS: The incidence of bacterial meningitis has decreased following pneumococcal and meningococcal conjugate vaccine introduction. In the diagnosis of bacterial meningitis the clinical characteristics and laboratory parameters are of limited diagnostic accuracy and therefore cerebrospinal fluid analysis remains the principal contributor to the final diagnosis. The ESCMID guideline advises to start empiric treatment within one hour of arrival in all suspected meningitis cases, and choice of antibiotics needs to be differentiated according to the patient's age, risk factors, and local resistance rates of pneumococci. Dexamethasone is the only proven adjunctive treatment and should be started together with the antibiotics. The follow-up of surviving patients should include evaluation for hearing loss and pneumococcal vaccination to prevent recurrences. Future perspectives include further development and implementation of vaccines, and new treatments aimed at further reducing the inflammatory response. Studies on implementation of the new guideline should determine adherence and evaluate whether improved prognosis can be achieved by following protocolled management strategies.
Assuntos
Infecções Comunitárias Adquiridas , Meningites Bacterianas , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Humanos , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/tratamento farmacológico , Guias de Prática Clínica como AssuntoRESUMO
OBJECTIVES: To investigate sex-based differences in clinical features, causative pathogens, outcome and treatment of adult community-acquired meningitis. METHODS: From January 2006 to July 2014, we prospectively investigated sex-based differences in clinical features, causative pathogens, outcome and treatment of adult community-acquired meningitis in a nationwide cohort study in the Netherlands. Sex was analysed along with known predictors of unfavourable outcome using logistic regression. RESULTS: We evaluated 1412 episodes of meningitis, 707 (50%) in men. Men more often presented with a history of remote head injury (41/667 (6%) versus 14/658 (2%) women, p 0.0002) or alcoholism (61/652 (9%) versus 21/660 (3%) women, p <0.0001). Neck stiffness was less common in men (453/651 (70%) versus 524/671 (78%) women, p 0.0004). Despite greater illness severity, women were less likely to receive treatment in an intensive care unit (odds ratio (OR) 0.72, 95% CI 0.58-0.89, p 0.003) or mechanical ventilation (OR 0.67, 95% CI 0.54-0.85, p 0.001). Women exhibited higher serum inflammatory parameters than men (median C-reactive protein 211 versus 171, p 0.0001; median erythrocyte sedimentation rate 48 versus 33, p <0.0001). Corticosteroids improved prognosis in both sexes, but absolute risk reduction was higher in women (20% versus 15%, p 0.001), although we found no significant interaction between sex and dexamethasone (p 0.38). In the multivariable analysis, male sex was an independent predictor of unfavourable outcome (OR 1.34, 95% CI 1.03-1.75, p 0.03) and death (OR 1.47, 95% CI 1.04-2.07, p 0.03). CONCLUSIONS: Our findings show sex-based differences in adults with community-acquired bacterial meningitis. Male sex is an independent risk factor for adverse outcome. It is possible that sex-based differences in immune reaction could determine a distinct response to corticosteroids.
Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Meningites Bacterianas/epidemiologia , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Biomarcadores , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Comorbidade , Feminino , Humanos , Masculino , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/microbiologia , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Razão de Chances , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores Sexuais , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: Listeria monocytogenes is a food-borne pathogen that can cause meningitis. The listerial genotype ST6 has been linked to increasing rates of unfavourable outcome over time. We investigated listerial genetic variation and the relation with clinical outcome in meningitis. METHODS: We sequenced 96 isolates from adults with listerial meningitis included in two prospective nationwide cohort studies by whole genome sequencing, and evaluated associations between bacterial genetic variation and clinical outcome. We validated these results by screening listerial genotypes of 445 cerebrospinal fluid and blood isolates from patients over a 30-year period from the Dutch national surveillance cohort. RESULTS: We identified a bacteriophage, phiLMST6 co-occurring with a novel plasmid, pLMST6, in ST6 isolates to be associated with unfavourable outcome in patients (p 2.83e-05). The plasmid carries a benzalkonium chloride tolerance gene, emrC, conferring decreased susceptibility to disinfectants used in the food-processing industry. Isolates harbouring emrC were growth inhibited at higher levels of benzalkonium chloride (median 60 mg/L versus 15 mg/L; p <0.001), and had higher MICs for amoxicillin and gentamicin compared with isolates without emrC (both p <0.001). Transformation of pLMST6 into naive strains led to benzalkonium chloride tolerance and higher MICs for gentamicin. CONCLUSIONS: These results show that a novel plasmid, carrying the efflux transporter emrC, is associated with increased incidence of ST6 listerial meningitis in the Netherlands. Suggesting increased disease severity, our findings warrant consideration of disinfectants used in the food-processing industry that select for resistance mechanisms and may, inadvertently, lead to increased risk of poor disease outcome.
Assuntos
Anti-Infecciosos Locais/farmacologia , Compostos de Benzalcônio/farmacologia , Farmacorresistência Bacteriana , Listeria monocytogenes/efeitos dos fármacos , Listeria monocytogenes/genética , Meningite por Listeria/microbiologia , Meningite por Listeria/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Estudos de Coortes , Feminino , Variação Genética , Genoma Bacteriano , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Listeria monocytogenes/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Países Baixos , Avaliação de Resultados da Assistência ao Paciente , Filogenia , Plasmídeos/genética , Polimorfismo de Nucleotídeo Único , Vigilância da População , Adulto JovemRESUMO
In a prospective nationwide cohort study performed in the Netherlands from 2006 to 2014 we analysed clinical and laboratory characteristics of adults with community-acquired bacterial meningitis who underwent repeat lumbar puncture. Repeat lumbar puncture was performed in 124 of 1490 included episodes (8%), most commonly because of clinical deterioration (42%). Median cerebrospinal fluid (CSF) leucocyte count on admission was 1473 cells/mm(3). Median CSF cell count showed a decrease of 19% when repeated within 2 days; of 84% within 3-7 days, of 93% within 8-14 days and of 98% within 15-21 days. Repeat lumbar puncture confirmed the diagnosis of meningitis in eight patients with normal initial CSF examination. Repeat CSF cultures yielded bacteria in nine patients, which led to identification of an underlying source of infection in two. We conclude that repeat lumbar puncture is performed in a small proportion of adults. Although it should not be seen as routine it can be useful in selected cases to confirm diagnosis, to exclude relapsing or persistent infection, or for therapeutic purpose in communicating hydrocephalus.
Assuntos
Testes Diagnósticos de Rotina/métodos , Meningites Bacterianas/diagnóstico , Punção Espinal/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bactérias/classificação , Bactérias/isolamento & purificação , Líquido Cefalorraquidiano/citologia , Líquido Cefalorraquidiano/microbiologia , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Países Baixos , Estudos Prospectivos , Adulto JovemRESUMO
Bacterial meningitis is a disease with a high morbidity and mortality. It may be caused by the zoonotic pathogen Capnocytophaga canimorsus, which is part of the commensal oral flora in dogs and cats. We report three cases of C. canimorsus meningitis in a nationwide cohort study of bacterial meningitis patients and performed a review of the literature. Three episodes of C. canimorsus meningitis were identified in three patients included in a nationwide cohort study from 2006 through 2014. The calculated annual incidence was 0.03 per million adults. When combined with the literature, 33 patients were identified of which 28 were male (85%). The median age was 63 years, and 13 (42%) were immunocompromised, which consisted of alcoholism in 7 (21%). Animal contact could be established in 29 of 30 patients (93%) and consisted of dog bites in 22 of 29 (76%). One patient died (3%) and 8 had neurological sequelae upon discharge (25%), most often hearing loss (n = 6, 19%). Capnocytophaga canimorsus meningitis is associated with dog bites. Although mortality is relatively low, survivors often have neurological sequelae.
Assuntos
Infecções por Flavobacteriaceae/microbiologia , Meningites Bacterianas/microbiologia , Adulto , Idoso , Animais , Cães , Flavobacteriaceae , Infecções por Flavobacteriaceae/patologia , Humanos , Masculino , Meningites Bacterianas/etiologia , Pessoa de Meia-Idade , ZoonosesRESUMO
We performed a nationwide prospective cohort study on the epidemiology and clinical features of community-acquired bacterial meningitis. Patients with a medical history of autologous or allogeneic hematopoietic stem cell transplantation (HSCT) were identified from the cohort performed from March 2006 to October 2014. Fourteen of 1449 episodes (1.0%) of bacterial meningitis occurred in patients with a history of HSCT. The incidence of bacterial meningitis in HSCT recipients was 40.4 per 100 000 patients per year (95% confidence interval (CI) 23.9-62.2), which is 30-fold (95% CI 18-51; P<0.001) higher compared with persons without HSCT. Incidence was higher in allogeneic HSCT compared with autologous HSCT (70.0 vs 15.8 per 100 000 patients per year). Causative organisms were Streptococcus pneumoniae in 11 patients, Neisseria meningitidis in two and Streptococcus mitis in one patient. Mortality was 3 of 14 (21%) and 6 of 11 (55%) survivors had sequelae. Nine of 11 patients (82%) with pneumococcal meningitis were infected with a serotype included in the 23-valent pneumococcal polysaccharide vaccine, of whom four developed meningitis despite vaccination. In conclusion, HSCT recipients have a substantially increased risk compared with the general population of acquiring bacterial meningitis, which is mostly due to S. pneumoniae, and disease is associated with high mortality and morbidity. Vaccination is important to prevent disease although vaccine failures did occur.