Invasive Meningococcal Disease: What We Should Know, Before It Comes Back.

BACKGROUND: Invasive meningococcal disease (IMD), sepsis and/or meningitis continues to be a public health problem, with mortality rates ranging from 5% to 16%. The aim of our study was to further knowledge about IMD with a large series of cases occurring over a long period of time, in a cohort with a high percentage of adult patients. METHODS: Observational cohort study of patients with IMD between 1977 hand 2013 at our hospital, comparing patients with only sepsis and those with meningitis and several degrees of sepsis. The impact of dexamethasone and prophylactic phenytoin was determined, and an analysis of cutaneous and neurological sequelae was performed. RESULTS: A total of 527 episodes of IMD were recorded, comprising 57 cases of sepsis (11%) and 470 of meningitis with or without sepsis (89%). The number of episodes of IMD decreased from 352 of 527 (67%) in the first to 20 of 527 (4%) in the last quarter (P < .001). Thirty-three patients died (6%): 8 with sepsis (14%) and 25 with meningitis (5%) (P = .02). Cutaneous and neurological sequelae were present in 3% and 5% of survivors of sepsis and meningitis, respectively. The use of dexamethasone was safe and resulted in less arthritis, and patients given prophylactic phenytoin avoided seizures. CONCLUSIONS: The frequency of IMD has decreased sharply since 1977. Patients with sepsis only have the highest mortality and complication rates, dexamethasone use is safe and can prevent some arthritis episodes, and prophylactic phenytoin might be useful in a selected population. A rapid response and antibiotic therapy may help improve the prognosis.

Invasive meningococcal disease: Impact of short course therapy. A DOOR/RADAR study.

BACKGROUND: Invasive meningococcal disease is a severe infection. The appropriate duration of antibiotic therapy is not well established. METHODS: Two hundred and sixty-three consecutive patients with invasive meningococcal disease treated with 4 days' antibiotic therapy were compared with 264 consecutive patients treated previously at the same center with 7 days' antibiotic therapy. A Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR) study was also performed. RESULTS: No relapses were recorded in any patient. Patients on the 4-day course were 63% female, with a median age of 23 years old (IQR 16-54) and patients on the 7-day course were 61% female, with a median age of 17 years old (IQR 12-43). Case fatality rate was 7% in the 4-d patients and 6% in the 7-d patients (p = 0.582). Neurological sequelae were recorded in 6% of the 4-d group and in 7% of the 7-d group ((p = 0.509) and cutaneous sequelae in 3% in both groups. There were no statistical significant differences between the groups in terms of clinical characteristics, laboratory findings or complications. The probability that a patient had a randomly chosen DOOR better with the 4-day regimen than with the 7-day regimen was 80.4% [95% CI 80.1-80.7%]. CONCLUSION: Invasive meningococcal disease may be successfully treated with a four-day course of antibiotic therapy without relapses.

Toscana virus infection in Catalonia (Spain).

Toscana virus (TOSV), an arthropod-borne phlebovirus, is an important agent of acute meningitis and meningoencephalitis in the Mediterranean area. The epidemiology of the infection in humans in Catalonia is at present unknown. In this study, we found a seroprevalence of infection of 6%, and 2 clinical cases were detected by serology and/or PCR.

Rhombencephalitis: a series of 97 patients.

The term rhombencephalitis refers to inflammatory diseases affecting the hindbrain (brainstem and cerebellum). Rhombencephalitis has a wide variety of etiologies, some of them potentially severe and life threatening without proper early treatment. In this retrospective observational study, we reviewed the records of consecutively hospitalized patients at University Hospital of Bellvitge (Barcelona, Spain) from January 1990 to December 2008. Rhombencephalitis was defined as a brainstem and/or cerebellar condition demonstrated clinically or by neuroimaging, with pleocytosis (>4 cells/mm) in cerebrospinal fluid. Ninety-seven patients (48 female; mean age, 37 yr; range, 14-79 yr) fulfilled these criteria. We reviewed their clinical, cerebrospinal fluid, and radiologic characteristics. The mean follow-up was 5 years (range, 0-20 yr). The etiologies of rhombencephalitis were as follows: unknown cause (n = 31), multiple sclerosis (n = 28), Behçet disease (n = 10), Listeria monocytogenes infection (n = 9), paraneoplastic syndrome (n = 6) (3 cases associated with anti-Yo antibodies and 3 with anti-Tr antibodies), Epstein-Barr virus (n = 4), tuberculosis (n = 2), pneumococcal infection (n = 2), systemic lupus erythematosus (n = 1), lymphoma (n = 1), Brucella species infection (n = 1), JC virus (n = 1), and relapsing polychondritis (n = 1). Certain clinical, cerebrospinal fluid, and radiologic characteristics that are commonly seen in some of these etiologies can guide us in the first approach to the etiologic diagnosis of rhombencephalitis.

Three-year multicenter surveillance of community-acquired Listeria monocytogenes meningitis in adults.

BACKGROUND: Listeria monocytogenes is the third most frequent cause of bacterial meningitis. The aim of this study is to know the incidence and risk factors associated with development of acute community-acquired Lm meningitis in adult patients and to evaluate the clinical features, management, and outcome in this prospective case series. METHODS: A descriptive, prospective, and multicentric study carried out in 9 hospitals in the Spanish Network for Research in Infectious Diseases (REIPI) over a 39-month period. All adults patients admitted to the participating hospitals with the diagnosis of acute community-acquired bacterial meningitis (Ac-ABM) were included in this study. All these cases were diagnosed on the basis of a compatible clinical picture and a positive cerebrospinal fluid (CSF) culture or blood culture. The patients were followed up until death or discharge from hospital. RESULTS: Two hundred and seventy-eight patients with Ac-ABM were included. Forty-six episodes of Lm meningitis were identified in 46 adult patients. In the multivariate analysis only age (OR 1.026; 95% CI 1.00-1.05; p = 0.042), immunosuppression (OR 2.520; 95% CI 1.05-6.00; p = 0.037), and CSF/blood glucose ratio (OR 39.42; 95% CI 4.01-387.50; p = 0.002) were independently associated with a Lm meningitis. The classic triad of fever, neck stiffness and altered mental status was present in 21 (49%) patients, 32% had focal neurological findings at presentation, 12% presented cerebellum dysfunction, and 9% had seizures. Twenty-nine (68%) patients were immunocompromised. Empirical antimicrobial therapy was intravenous ampicillin for 34 (79%) of 43 patients, in 11 (32%) of them associated to aminoglycosides. Definitive ampicillin plus gentamicin therapy was significantly associated with unfavourable outcome (67% vs 28%; p = 0.024) and a higher mortality (67% vs 32%; p = 0.040).The mortality rate was 28% (12 of 43 patients) and 5 of 31 (16.1%) surviving patients developed adverse clinical outcome. CONCLUSIONS: Elderly or immunocompromised patients, and a higher CSF/blood glucose ratio in patients with Ac-ABM must alert clinicians about Lm aetiology. Furthermore, we observed a high incidence of acute community-acquired Lm meningitis in adults and the addition of aminoglycosides to treatment should be avoid in order to improve the patients' outcome. Nevertheless, despite developments in intensive care and antimicrobial therapy, this entity is still a serious disease that carries high morbidity and mortality rates.

Peripheral facial palsy after varicella. Report of two cases and review of the literature

Background There is little information regarding peripheral facial palsy (PFP) as a complication of varicella. We describe 2 adults who developed varicella-related PFP, in 1 case as a part of Guillain-Barré syndrome (GBS), and review all reported cases of this condition. Methods MEDLINE search. ResultsA total of 10 cases of isolated varicella-associated PFP have been reported. PFP was diagnosed 3 to 16 days after the onset of skin manifestations. Four (40%) patients developed bilateral PFP. Two patients had varicella meningitis; both were PCR-positive for varicella-zoster virus (VZV) in CSF. CSF IgG antibodies against VZV were demonstrated in 2 other patients. One patient had slight CSF albumino-cytological dissociation. Five patients were treated with acyclovir, and 3 of them also received corticosteroids. Most patients showed a favorable course, with partial or complete recovery of PFP. Results In addition, 17 patients with GBS after the onset of varicella were reviewed. Mean time to the development of GBS after varicella onset was 9.3 days, and 9 patients had PFP as a part of the neurologic picture. Seven patients (41%) developed respiratory failure requiring mechanical ventilation. Six patients received treatment with intravenous immunoglobulin, and all of them showed optimal evolution. One patient died. Conclusions Isolated PFP and GBS are rare peripheral nerve complications after varicella. Treatment should be individualized for each case, depending on the severity of the condition and the clinical evolution (AU)

Antecedentes Existe escasa información referente a la parálisis facial periférica (PFP) como complicación posvaricela. En este artículo se describen 2 casos, uno de ellos en relación al Sd. de Guillain-Barré (SGB) y se revisa lo descrito anteriormente en la literatura. Métodos Revisión en MEDLINE. Resultados Se han descrito 10 casos de PFP relacionada con varicela. La PFP se ha diagnosticado de 3 a 16 días después de la aparición de las lesiones cutáneas. Cuatro (40%) pacientes desarrollaron PFP bilateral. Dos pacientes tuvieron meningitis por varicela, ambos tenían PCR de virus varicella-zoster positivo en LCR. Se documentó la presencia de anticuerpos Ig G en LCR frente VZV en otros 2 pacientes. Un paciente tenía disociación albúmino-citológica en LCR. Cinco pacientes fueron tratados con aciclovir y 3, concomitantemente, con corticoides. La mayoría de pacientes mostró una buena evolución, con una resolución total o parcial de la PFP. A su vez, analizamos 17 pacientes con pacientes SGB después de varicela. El tiempo medio de desarrollo el SGB fue de 9,3 días. Nueve pacientes presentaron PFP en relación con el episodio de SGB. Siete (41%) pacientes presentaron insuficiencia respiratoria grave que precisó de ventilación mecánica. Seis pacientes recibieron tratamiento con inmunoglobulinas, todos ellos con una buena evolución. Un paciente falleció. Conclusiones La PFP y el SGB son complicaciones poco frecuentes de después de la varicela. El tratamiento se debe individualizar en cada caso, dependiendo de la gravedad y la evolución clínica (AU)

Espondilodiscitis tuberculosa después de una punción lumbar / Tuberculous spondylodiscitis after a lumbar puncture

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Peripheral facial palsy after varicella. Report of two cases and review of the literature.

BACKGROUND: There is little information regarding peripheral facial palsy (PFP) as a complication of varicella. We describe 2 adults who developed varicella-related PFP, in 1 case as a part of Guillain-Barré syndrome (GBS), and review all reported cases of this condition. METHODS: MEDLINE search. RESULTS: A total of 10 cases of isolated varicella-associated PFP have been reported. PFP was diagnosed 3 to 16 days after the onset of skin manifestations. Four (40%) patients developed bilateral PFP. Two patients had varicella meningitis; both were PCR-positive for varicella-zoster virus (VZV) in CSF. CSF IgG antibodies against VZV were demonstrated in 2 other patients. One patient had slight CSF albumino-cytological dissociation. Five patients were treated with acyclovir, and 3 of them also received corticosteroids. Most patients showed a favorable course, with partial or complete recovery of PFP. In addition, 17 patients with GBS after the onset of varicella were reviewed. Mean time to the development of GBS after varicella onset was 9.3 days, and 9 patients had PFP as a part of the neurologic picture. Seven patients (41%) developed respiratory failure requiring mechanical ventilation. Six patients received treatment with intravenous immunoglobulin, and all of them showed optimal evolution. One patient died. CONCLUSIONS: Isolated PFP and GBS are rare peripheral nerve complications after varicella. Treatment should be individualized for each case, depending on the severity of the condition and the clinical evolution.

Absceso cerebral del adulto por Listeria monocytogenes: presentación de 6 casos y revisión de la literatura médica / Brain abscess due to Listeria monocytogenes in adults: Six cases and review of the literature

Introducción Listeria monocytogenes es un bacilo grampositivo, con especial tropismo por el sistema nervioso central (SNC). El absceso cerebral por Listeria es una entidad insuficientemente conocida, a pesar de que representa el 10% de las infecciones del SNC por este microorganismo. Métodos A continuación se presentan 6 pacientes con absceso cerebral por L. monocytogenes que ingresaron de forma consecutiva en el Hospital Universitario de Bellvitge durante los últimos 7 años. Se revisa también la literatura médica de los últimos 40 años hallando 70 pacientes con absceso cerebral por Listeria. Se describen las características epidemiológicas, clínicas, microbiológicas, radiológicas y evolutivas. Resultados El absceso cerebral por Listeria es una entidad de mal pronóstico y con elevada mortalidad. Conclusión Se requiere un elevado índice de sospecha para su detección precoz y tratamiento antibiótico correcto que redunde en una mejor evolución. La sospecha debe fundamentarse en la presencia de fiebre o febrícula junto con focalidad neurológica, sobre todo en pacientes inmunodeprimidos o diabéticos (AU)

Introduction Listeria monocytogenes is a gram-positive bacillus, with special tropism for the central nervous system (CNS). Brain abscess caused by Listeria has not been extensively studied, although it accounts for 10% of CNS infections due to this microorganism. Methods We present 6 patients with Listeria brain abscess consecutively admitted to Bellvitge University Hospital over the last 7 years. A literature review covering 40 years retrieved 70 patients with Listeria brain abscess. The epidemiologic, clinical, microbiological, and radiological findings related to this entity, and the outcome features are described. Results Brain abscess due to Listeria has a poor prognosis and is associated with elevated mortality. Conclusion A high index of suspicion is needed to reach an early diagnosis and establish appropriate antibiotic treatment, which will improve the outcome of this condition. Suspicion is based on the presence of fever and neurological symptoms, particularly in immunodepressed or diabetic patients (AU)

[Brain abscess due to Listeria monocytogenes in adults: six cases and review of the literature]. / Absceso cerebral del adulto por Listeria monocytogenes: presentación de 6 casos y revisión de la literatura médica.

INTRODUCTION: Listeria monocytogenes is a gram-positive bacillus, with special tropism for the central nervous system (CNS). Brain abscess caused by Listeria has not been extensively studied, although it accounts for 10% of CNS infections due to this microorganism. METHODS: We present 6 patients with Listeria brain abscess consecutively admitted to Bellvitge University Hospital over the last 7 years. A literature review covering 40 years retrieved 70 patients with Listeria brain abscess. The epidemiologic, clinical, microbiological, and radiological findings related to this entity, and the outcome features are described. RESULTS: Brain abscess due to Listeria has a poor prognosis and is associated with elevated mortality. CONCLUSION: A high index of suspicion is needed to reach an early diagnosis and establish appropriate antibiotic treatment, which will improve the outcome of this condition. Suspicion is based on the presence of fever and neurological symptoms, particularly in immunodepressed or diabetic patients.

Fungal postoperative spondylodiscitis due to Scedosporium prolificans.

BACKGROUND CONTEXT: Postoperative fungal spondylodiscitis is a rare infectious disease. PURPOSE: We report the first case of postoperative spondylodiscitis because of Scedosporium prolificans and review postoperative vertebral infection caused by fungi. STUDY DESIGN/SETTING: Medline search. METHODS: Case report and literature review. RESULTS: On reviewing the cases of postoperative fungal spondylodiscitis reported so far in the literature, we found eight were caused by mold, and five by yeast. Clinically, the disease presents similar to postoperative vertebral osteomyelitis caused by bacteria, and a high clinical index of suspicion may be required to perform appropriate cultures to establish a diagnosis. Our review revealed a significant number of cases that were cured after surgical debridement and/or antifungal therapy. CONCLUSIONS: On the basis of this limited assessment, it appears that the clinical course and prognosis of postoperative fungal spondylodiscitis is similar to that reported for postoperative pyogenic spondylodiscitis.

Adult herpes simplex encephalitis: fifteen years' experience.

INTRODUCTION: Herpes simplex encephalitis (HSE) is the most frequent cause of sporadic necrotizing encephalitis in adults. The aim of this study is to describe the characteristics of HSE and the factors influencing its outcome. MATERIAL AND METHODS: Retrospective study of patients diagnosed with HSE in a tertiary care teaching hospital over a 15-year period. Diagnosis was based on a consistent clinical profile for HSE, plus either a PCR-positive CSF HSV study or consistent brain neuroimaging findings. Patients were divided into 2 groups according to the modified Rankin Scale: good outcome (Grades <=2) and poor outcome (Grades >=3). RESULTS: Thirty-five patients were included. Mean age was 53.9 years. More than half presented febricula or fever, headache, disorientation, behavioral changes, decreased level of consciousness, or neurological deficit. CSF glucose concentration was normal in all patients and WBC count was normal in 8 (23%). PCR for HSV was positive in 92% and cranial MRI was suggestive of HSE in 100% of patients. Mortality was 8.6%. In relation to outcome, age (OR=1.079; 95% CI, 1.023-1.138) and serum albumin level at admission (OR=0.87; 95% CI, 0.794-0.954) were independent prognostic factors at discharge. At 6 months, days of fever after initiation of acyclovir therapy (OR=1.219; 95% CI, 1.046-1.422) and serum albumin level at admission (OR=0.917; 95% CI, 0.87-0.967) were independent prognostic factors. CONCLUSIONS: Normal brain MRI or detection of low CSF glucose concentration requires consideration of diagnoses other than HSE. Age, serum albumin level at admission, and days of fever after initiation of acyclovir therapy were independent prognostic factors of the disease.

Encefalitis herpética del adulto: experiencia de 15 años / Adult herpes simplex encephalitis: Fifteen years’ experience

Introduction: Herpes simplex encephalitis (HSE) is the most frequent cause of sporadic necrotizing encephalitis in adults. The aim of this study is to describe the characteristics of HSE and the factors influencing its outcome. Material and methods: Retrospective study of patients diagnosed with HSE in a tertiary care teaching hospital over a 15-year period. Diagnosis was based on a consistent clinical profile for HSE, plus either a PCR-positive CSF HSV study or consistent brain neuroimaging findings. Patients were divided into 2 groups according to the modified Rankin Scale: good outcome (Grades ≤2) and poor outcome (Grades ≥3).Results: Thirty-five patients were included. Mean age was 53.9 years. More than half presented febricula or fever, headache, disorientation, behavioral changes, decreased level of consciousness, or neurological deficit. CSF glucose concentration was normal in all patients and WBC count was normal in 8 (23%). PCR for HSV was positive in 92% and cranial MRI was suggestive of HSE in 100% of patients. Mortality was 8.6%. In relation to outcome, age (OR=1.079; 95% CI, 1.023–1.138) and serum albumin level at admission (OR=0.87; 95% CI, 0.794–0.954) were independent prognostic factors at discharge. At 6 months, days of fever after initiation of acyclovir therapy (OR=1.219; 95% CI, 1.046–1.422) and serum albumin level at admission (OR=0.917; 95% CI, 0.87–0.967) were independent prognostic factors.Conclusions: Normal brain MRI or detection of low CSF glucose concentration requires consideration of diagnoses other than HSE. Age, serum albumin level at admission, and days of fever after initiation of acyclovir therapy were independent prognostic factors of the disease (AU)

Introducción: la encefalitis herpética (EH) es la causa más frecuente de encefalitis necrosante esporádica del adulto. El objetivo es describir las características de la EH y sus factores pronósticos. Material y métodos: estudio retrospectivo de los pacientes ingresados en un hospital universitario de tercernivel y diagnosticados de EH durante un periodo de 15 años. El diagnóstico se estableció según el cuadro clínico compatible, junto con una prueba de reacción en cadena de la polimerasa(PCR) positiva para el virus del herpes simple (VHS) y/o una prueba de neuro imagen compatible. Se dividió a los pacientes en dos grupos de acuerdo con la Escala de Rankin modificada: buen pronóstico (grados p2) y mal pronóstico(grados X3).Resultados: se estudió a un total de 35 pacientes con una media de edad de 53,9 años. La mayoría presentaba febrícula o fiebre, cefalea, desorientación, alteración conductual, disminución del nivel deconciencia o focalidad neurológica. Todos los pacientes presentaron normoglucorraquia y el recuento leucocitario en el líquido cefalorraquídeo fue normal en 8 (23%)pacientes. La PCR para VHS resultó positiva en el 92% y la resonancia magnética (RM) craneal fue compatible con EH en el 100% de los pacientes. La mortalidad fue del 8,6%. La edad (odds ratio [OR] ¼ 1,079; intervalo de confianza [IC]del 95%, 1,023–1,138) y las concentraciones de seroalbúmina al ingreso (OR ¼ 0,87; IC del 95%, ,0,794–0,954) resultaron factores pronósticos independientes al alta. A los 6 meses, los días de fiebre después de la instauración del tratamiento con aciclovir (OR ¼ 1,219; ICdel95%, 1,046–1,422) y las concentraciones de seroalbúmina al ingreso (OR ¼ 0,917; IC del 95%, 0,87–0,967) resultaron factores pronósticos independientes (AU)

Infección criptocócica y tratamiento inmunosupresor / Cryptococcal disease and immunosuppressive treatment

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Evaluation of ceftriaxone, vancomycin and rifampicin alone and combined in an experimental model of meningitis caused by highly cephalosporin-resistant Streptococcus pneumoniae ATCC 51916.

OBJECTIVES: The aim of the study was to assess the in vitro and in vivo efficacy of ceftriaxone, vancomycin and rifampicin alone and combined against Streptococcus pneumoniae ATCC 51916 (MIC of ceftriaxone: 32 mg/L). METHODS: In vitro killing curves were performed with clinically achievable CSF antibiotic concentrations. In the rabbit model of pneumococcal meningitis, we studied the efficacy of and effects on inflammation of treatment with ceftriaxone 100 mg/kg/day, vancomycin 30 mg/kg/day and rifampicin 15 mg/kg/day, alone and combined, over a 26 h period. RESULTS: Time-kill curves showed that vancomycin was bactericidal, and ceftriaxone and rifampicin produced a bacteriostatic effect. An additive effect was observed when combinations of ceftriaxone plus vancomycin were studied at subinhibitory concentrations. Emergence of resistance to rifampicin was detected both when rifampicin was studied alone and when combined with ceftriaxone or vancomycin. In the rabbit meningitis model, ceftriaxone was bacteriostatic, whereas rifampicin and vancomycin were bactericidal at 24 h. Although not synergistic, the combinations of ceftriaxone plus vancomycin or rifampicin, and vancomycin plus rifampicin, improved the efficacy of any antibiotic tested alone--all combinations were bactericidal from 6 h--and significantly decreased inflammatory parameters in CSF compared with control and ceftriaxone groups. CONCLUSION: Ceftriaxone plus vancomycin, and vancomycin plus rifampicin appeared to be effective in the therapy of experimental pneumococcal meningitis caused by highly cephalosporin-resistant strains such as ATCC 51916. Our results provide an experimental basis for using these combinations as empirical therapy for pneumococcal meningitis, regardless of the degree of cephalosporin resistance of the causative strain.

Absceso cerebral por Eikenella corrodens y Streptococcus intermedius asociado a tumor carcinoide del tubo digestivo / Brain abscess caused by Eikenella corrodens and Streptococcus intermedius associated wit bowel carcinoid tumour

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