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Rapport og anbefaling vedrørende lumbalpunktur, blodfortyndende behandling og akut bakteriel meningitis. Udarbejdet af en arbejdsgruppe nedsat af Dansk Selskab for Infektionsmedicin vedrørende neuroinfektioner.
Udgiver: Dansk Selskab for Infektionsmedicin 2018
Arbejdsgruppe: Anne-Mette Lebech, Birgitte Rønde Hansen, Christian Brandt, Hans Rudolph von Lüttichau, Jacob Bodilsen, Jannik Helweg-Larsen, Lothar Wiese, Lykke Larsen, Trine Mogensen.
Udgiver: Dansk Selskab for Infektionsmedicin
Arbejdsgruppe: Anne-Mette Lebech, Birgitte Rønde Hansen, Christian Brandt, Hans Rudolf von Lüttichau, Jacob Bodilsen, Lothar Wiese, Lykke Larsen, Trine Mogensen.
Udgiver: Dansk Selskab for Infektionsmedicin
Arbejdsgruppe: Anne-Mette Lebech, Birgitte Rønde Hansen, Christian Brandt, Hans Rudolph von Lüttichau, Jacob Bodilsen, Jannick Helweg-Larsen, Lothar Wiese, Lykke Larsen, Trine Mogensen.
Klinik, diagnostik og behandling af Lyme Borreliose i Danmark.
Forfattergruppen er nedsat af Dansk Selskab for Klinisk Mikrobiologi, Dansk Selskab for Infektionsmedicin og Dansk Neurologisk Selskab.
Tværregional vejledning vedrørende akut bakteriel (purulent) meningitis hos voksne
Vejledning om forebyggelse ved tilfælde af Meningokoksygdom
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Nocardiosis is an uncommon disease caused by aerobic gram-positive bacteria Nocardia spp. Although it is usually an opportunistic infection affecting immunocompromised patients, even one third of cases occur in immunocompetent persons. The aim of the study was to describe the course of chronic meningitis due to Nocardia infection.
A 52-year-old patient, chalk miner, suffered from a chronic meningitis caused by an extremely rare pathogen. The patient’s history was complicated and diagnostic process covered multiple examinations and consultations. Initially Kocuria rosea was cultured, yet after molecular examination the result was verified to Nocardia farcinica. Targeted antibiotic treatment was implemented, which resulted in gradual improvement of patients condition. A full recovery was achieved after one year antibiotic therapy.
Nocardia farcinica is an uncommon but possible cause of chronic meningitis.
In the case of a chronic meningitis of unknown origin multiple cerebrospinal fluid cultures should be performed as the identification of pathogen may be crucial for patient’s recovery.
In case of unusual culture, such as Kocuria spp. PCR should be performed.
Sarah Tubiana, Emmanuelle Varon, Charlotte Biron, Marie-Cecile Ploy, Bruno Mourvillier, Muhamed-Kheir Taha, Mathieu Revest, Claire Poyart, Guillaume Martin-Blondel, Marc Lecuit, Eric Cua, Blandine Pasquet, Marie Preau, Bruno Hoen, Xavier Duval, the COMBAT study group, Principal investigator, Steering Committee, Scientific committee: steering committee and the following members, COMBAT Clinical Centers, Coordination and statistical analyses (Clinical trial unit, Hôpitaux Universitaires Paris Nord Val de Sein
To identify factors associated with unfavorable in-hospital outcome (death or disability) in adults with community-acquired bacterial meningitis (CABM).
Pullen M, Hullsiek K, Rhein J, et al.
AbstractBackgroundIn cryptococcal meningitis phase two clinical trials, early fungicidal activity (EFA) of Cryptococcus clearance from cerebrospinal fluid (CSF) is used as a surrogate endpoint for all-cause mortality. The FDA allows for using surrogate endpoints for accelerated regulatory approval, but EFA as a surrogate endpoint requires further validation. We examined the relationship between rate of CSF Cryptococcus clearance (EFA) and mortality through 18-weeks.MethodsWe pooled individual-level CSF data from three sequential cryptococcal meningitis clinical trials conducted during 2010-2017. All 738 subjects received amphotericin + fluconazole induction therapy and had serial quantitative CSF cultures. The log10-transformed colony forming units (CFUs) per mL CSF were analyzed by general linear regression versus day of culture over the first 10 days.ResultsMortality through 18-weeks was 37% for EFA >=0.60 (n=170), 36% for 0.40-0.59 (n=182), 39% for 0.30-0.39 (n=112), 35% for 0.20-0.29 (n=87), and 50% for those with EFA
Angharad G Davis, Robert J Wilkinson
Tuberculous meningitis is the most serious manifestation of tuberculosis, with mortality in approximately 50% of HIV co-infected people.1 A major factor contributing to the poor outcome of tuberculous meningitis is delayed diagnosis due to a lack of rapid, accurate diagnostic tests. Until recently, these tests were restricted to smear microscopy of cerebrospinal fluid (CSF) and microbiological culture. The former tends operationally to be of low sensitivity and the latter often renders a result too late to be clinically meaningful.
Joseph Donovan, Do Dang Anh Thu, Nguyen Hoan Phu, Vu Thi Mong Dung, Tran Phu Quang, Ho Dang Trung Nghia, Pham Kieu Nguyet Oanh, Tran Bao Nhu, Nguyen Van Vinh Chau, Vu Thi Ngoc Ha, Vu Thi Ty Hang, Dong Huu Khanh Trinh, Ronald B Geskus, Le Van Tan, Nguyen Thuy Thuong Thuong, Guy E Thwaites
Xpert Ultra was not statistically superior to Xpert for the diagnosis of tuberculous meningitis in HIV-uninfected and HIV-infected adults. A negative Xpert Ultra or Xpert test does not rule out tuberculous meningitis. New diagnostic strategies are urgently required.
Fiona V Cresswell, Lillian Tugume, Nathan C Bahr, Richard Kwizera, Ananta S Bangdiwala, Abdu K Musubire, Morris Rutakingirwa, Enock Kagimu, Edwin Nuwagira, Edward Mpoza, Joshua Rhein, Darlisha A Williams, Conrad Muzoora, Daniel Grint, Alison M Elliott, David B Meya, David R Boulware, ASTRO-CM team
Xpert Ultra detected tuberculous meningitis with higher sensitivity than Xpert and MGIT culture in this HIV-positive population. However, with a negative predictive value of 93%, Xpert Ultra cannot be used as a rule-out test. Clinical judgment and novel highly sensitive point-of-care tests are still required.
Meningitis is a very rare atypical presenting feature of anti-NMDA receptor encephalitis. In our case report, we describe an unusual clinical presentation of anti-NMDA receptor encephalitis with a biphasic pattern of meningitis followed by encephalitis and discuss potential mechanisms underlying this presentation. We aim to widen the differential diagnosis to be considered in a patient presenting with clinical meningitis and pyrexia.
This is a case of a 33-year old Caucasian woman who initially presented with a lymphocytic meningitis attributed to a viral infection. She subsequently developed fluctuating consciousness, agitation, visual hallucinations, dyskinetic movements, a generalized tonic-clonic seizure, and autonomic instability. Investigations revealed a diagnosis of anti-NMDA receptor encephalitis secondary to a previously unidentified ovarian teratoma. She made an excellent recovery with immunotherapy and removal of the teratoma.
Clinicians should consider autoimmune encephalitides in individuals with meningitis, particularly where extensive investigations fail to identify a causative pathogen and there is rapid development of an encephalitic phenotype.
A well described case of the emergence of drug resistance in Streptococcus pneumoniae meningitis during therapy with ceftriaxone monotherapy with a low bactericidal concentration in the cerebrospinal fluid. Adherence to international guidelines could possibly prevented the emergence of this resistant isolate and the adverse outcome.
Bacillus cereus sometimes causes central nervous system infection, especially in compromised hosts. In cases of meningitis arising during neutropenia, CSF abnormalities tend to be subtle and can be easily overlooked, and mortality rate is high. We report a survived case of B. cereus meningitis/brain abscess in severe neutropenia, presenting as immune reconstitution syndrome.
A 54-year-old Japanese female with acute myelogenous leukemia developed B. cereus bacteremia and meningitis during consolidation chemotherapy. At the onset, she presented with mild meningism. She had marked leukocytopenia (WBC
Okurut, S., Meya, D. B., Bwanga, F., Olobo, J., Eller, M. A., Cham-Jallow, F., Bohjanen, P. R., Pratap, H., Palmer, B. E., Hullsiek, K. H., Manabe, Y. C., Boulware, D. R., Janoff, E. N.
Background: Activated B cells modulate infection by differentiating into pathogen-specific antibody-producing effector plasmablasts/plasma cells, memory cells and immune regulatory B cells. In this context, the B cell phenotypes that infiltrate the central nervous system during HIV and cryptococcal meningitis co-infection are ill defined.Methods: We characterized clinical parameters, mortality and B cell phenotypes in blood and CSF by flow cytometry in HIV-infected adults with cryptococcal (n=31), and non-cryptococcal meningitis (n=12), and heathy control subjects with neither infection (n=10).Results: Activation of circulating B cells (CD21low) was significantly higher in blood of subjects with HIV infection compared with healthy controls, and greater yet in matched CSF B cells (p
Aseptic meningitis epidemics may pose various health care challenges.
We describe the German enterovirus meningitis epidemics in the university hospital centers of Düsseldorf, Cologne and Berlin between January 1st and December 31st, 2013 in order to scrutinize clinical differences from other aseptic meningitis cases.
A total of 72 enterovirus (EV-positive) meningitis cases were detected in our multicenter cohort, corresponding to 5.8% of all EV-positive cases which were voluntarily reported within the National Enterovirus surveillance (EVSurv, based on investigation of patients with suspected aseptic meningitis/encephalitis and/or acute flaccid paralysis) by physicians within this period of time. Among these 72 patients, 38 (52.8%) were enterovirus positive and typed as echovirus (18 pediatric and 20 adult cases, median age 18.5 years; echovirus 18 (1), echovirus 2 (1), echovirus 30 (31), echovirus 33 (1), echovirus 9 (4)). At the same time, 45 aseptic meningitis cases in our cohort were excluded to be due to enteroviral infection (EV-negative). Three EV-negative patients were tested positive for varicella zoster virus (VZV) and 1 EV-negative patient for herpes simplex virus 2. Hospitalization was significantly longer in EV-negative cases. Cerebrospinal fluid analysis did not reveal significant differences between the two groups. After discharge, EV-meningitis resulted in significant burden of sick leave in our pediatric cohort as parents had to care for the children at home.
Voluntary syndromic surveillance, such as provided by the EVSurv in our study may be a valuable tool for epidemiological research. Our analyses suggest that EV-positive meningitis predominantly affects younger patients and may be associated with a rather benign clinical course, compared to EV-negative cases.
Giannoula S. Tansarli, Kimberle C. Chapin
The FilmArray® Meningitis/Encephalitis (ME) panel is a multiplex PCR assay which can detect the most commonly identified pathogens in central nervous system infections. It significantly decreases the time to diagnosis of ME and data has yielded several positive outcomes. However, in part, reports of both false positive and false negative detections have resulted in concerns about adoption.
N. Susilawathi et al.
Mizrahi, A., Marvaud, J. C., Pilmis, B., Nguyen Van, J. C., Couzigou, C., Bruel, C., Engrand, N., Le Monnier, A., Lambert, T.
We report a case of a 62-year old man treated for a Streptococcus pneumoniae meningitis by ceftriaxone and dexamethasone. After a neurological improvement, neurological degradation by vasculitis occurred, despite effective concentrations of ceftriaxone in serum and CSF. S. pneumoniae with increased MICs to third-generation-cephalosporins (3GC) was isolated from the ventricular fluid ten days after the isolation of the first strain. Isolates analysis showed that a mutation of penicillin-binding proteins in PBP2x has occurred under treatment.
Streptococcus oralis belongs to the Streptococcus mitis group and is part of the normal flora of the nasal and oropharynx (Koneman et al., The Gram-positive cocci part II: streptococci, enterococci and the ‘Streptococcus-like’ bacteria. Color atlas and textbook of diagnostic microbiology, 1997). Streptococcus oralis is implicated in meningitis in patients with decreased immune function or from surgical manipulation of the central nervous system. We report a unique case of meningitis by Streptococcus oralis in a 58-year-old patient with cerebral spinal fluid leak due to right sphenoid meningoencephalocele.
A 58-year-old female presented in the emergency department due to altered mental status, fevers, and nuchal rigidity. Blood cultures were positive for Streptococcus oralis. Magnetic resonance stereotactic imaging of head with intravenous gadolinium showed debris in lateral ventricle occipital horn and dural thickening/enhancement consistent with meningitis. There was also a right sphenoidal roof defect, and meningoencephalocele with cerebrospinal fluid leak as a result. The patient was treated with ceftriaxone and had endoscopic endonasal repair of defect. She had complete neurologic recovery 3 months later.
Cerebrospinal fluid leak puts patients at increased risk for meningitis. Our case is unique in highlighting Streptococcus oralis as the organism implicated in meningitis due to cerebrospinal fluid leak.
Vimal Kumar Paliwal, Animesh Das, Sucharita Anand and Prabhakar Mishra
Intravenous (IV) dexamethasone is recommended for 14 days in stage 1 and 28 days in stage 2/3 tuberculous meningitis (TBM). We used a different steroid protocol. We shifted TBM patients to oral steroids after 48 hours of sustained improvement on IV steroids (oral group). Patients who worsened after shifting to oral steroids were reinitiated on IV steroids. Once they showed a consistent improvement for 48 hours, the IV steroids were overlapped with oral steroids for 7–10 days to taper off IV steroids (overlap group). We compared total IV steroid days in our patients with the recommended treatment and identified predictors that favored the oral group. This was a retrospective study. We included 98 patients with TBM (66 in the overlap group and 32 in the oral group) from January 2013 to July 2018. The median IV steroid days were 9 days (interquartile range of 4–12; 2–3.5 days in the oral group and 10–11.5 days in the overlap group). The mortality rate was 6.1%. The logistic regression model showed that TBM patients with basal exudate, tuberculoma, and modified Rankin scale (mRS) < 3 had a higher probability for going to the oral group. We conclude that total IV steroid days can be reduced in TBM patients by our method of steroid use. Presence of basal exudates and tuberculoma may favor early shifting from IV to oral steroid, whereas higher mRS may require a relatively longer course of IV steroid.
Svensson E, Dian S, te Brake L, et al.
AbstractBackgroundIntensified antimicrobial treatment with higher rifampicin doses may improve outcome of tuberculous meningitis, but the desirable exposure and necessary dose are unknown. Our objective was to characterize the relationship between rifampicin exposures and mortality in order to identify optimal dosing for tuberculous meningitis.MethodsAn individual patient meta-analysis was performed on data from three Indonesian randomized controlled phase II trials comparing oral rifampicin 450mg (~10mg/kg) to intensified regimens including 750-1350mg orally, or a 600mg intravenous infusion. Pharmacokinetic data from plasma and CSF was analyzed with nonlinear mixed-effects modeling. Six-month survival was described with parametric time-to-event models.ResultsPharmacokinetic analyses included 133 individuals (1150 concentration measurements, 170 from CSF). The final model featured two disposition-compartments, saturable clearance and autoinduction. Rifampicin CSF concentrations were described by a partition coefficient (5.5% [95%CI 4.4-6.4]) and half-life for distribution plasma to CSF (2.1 h [1.3-2.9]). Higher CSF protein concentration increased the partition coefficient. Survival of 148 individuals (58 died, 15 drop-outs) was well described by an exponentially declining hazard, with lower age, higher baseline Glasgow Coma Scale score and higher individual rifampicin plasma exposure reducing the hazard. Simulations predicted an increase in 6-month survival from ~50% to ~70% upon increasing the oral rifampicin dose from 10 to 30mg/kg, and that higher doses would further increase survival.ConclusionsHigher rifampicin exposure substantially decreased the risk of death, and the maximal effect was not reached within the studied range. We suggest a rifampicin dose of at least 30mg/kg to be investigated in phase III clinical trials.
Invasive meningococcal disease (IMD) presenting with meningitis causes significant mortality and morbidity. Suppurative complications of serogroup B meningococcal sepsis are rare and necessitate urgent multidisciplinary management to mitigate long-term morbidity or mortality.
We present a rare case of invasive meningococcal disease in a 28-month old boy complicated by multiple abscess formation within a pre-existing antenatal left middle cerebral artery territory infarct. Past history was also notable for cerebral palsy with right hemiplegia, global developmental delay and West syndrome (infantile spasms). Two craniotomies were performed to achieve source control and prolonged antimicrobial therapy was necessary. The patient was successfully discharged following extensive multidisciplinary rehabilitation.
Longstanding areas of encephalomalacia in the left MCA distribution may have facilitated the development of multiple meningococcal serogroup B abscess cavities in the posterior left frontal, left parietal and left temporal lobes following an initial period of cerebritis and meningitis. A combination of chronic cerebral hypoperfusion and some degree of pre-existing necrosis in these areas, may also have facilitated growth of Neisseria meningitidis, leading ultimately to extensive cerebral abscess formation following haematogenous seeding during meningococcemia. In this case report we review similar cases of cerebral abscess or subdural empyema complicating serogroup B meningococcal meningitis.
Fiona Cresswell, Christoph Lange, Reinout van Crevel
Tuberculosis (TB) is the leading infectious cause of death globally. Meningitis accounts for 1-2% of TB cases (more in HIV-endemic settings), but kills or disables up to 50% or more of those affected . Tuberculous meningitis (TBM) is notoriously difficult to diagnose with conventional microbiological techniques due to the scarcity of bacilli and Mycobacterium tuberculosis DNA.
Cryptococcal meningitis is most commonly found in HIV-infected patients. In HIV-negative patients, its low incidence can lead to prolonged time to diagnosis. Detailed case reports of chronic cryptococcal meningitis are scarce, but could provide clues for earlier diagnosis in this patient category.
A 60-year old man presented June 2015 with intermittent headaches for several months without any fever. Initial work-up showed a leukocytosis, raised CSF opening pressure and raised leukocytes and protein in the CSF. An MRI revealed leptomeningeal contrast enhancement and cerebellar oedema. While malignancy and various infectious causes were excluded, the patient had a spontaneous clinical and radiological recovery. One year later, the patient returned with complaints of headaches. Also, cerebellar oedema and leptomeningeal contrast enhancement had recurred. Eventually in March 2017, the novel cryptococcal antigen lateral flow assay (CrAg LFA) was positive on CSF, and one colony of Cryptococcus neoformans was cultured from CSF. The patient was treated with the standard antifungal regimen which resulted in resolution of his headaches. In retrospect, the cryptococcal antigen test was already positive on a serum sample from June 2015. Interestingly, post-treatment immunological analysis revealed both a low mannose-binding lectin (MBL) concentration and low naïve CD4 counts.
We present a patient with cryptococcal meningitis in an HIV-negative patient with low MBL and low naïve CD4 count suffering a chronic relapsing meningo-encephalitis with relatively mild symptoms for around 2 years. In patients with an unexplained meningo-encephalitis such as this case, early performance of CrAg LFA on serum and/or CSF is an inexpensive and rapid method to reduce time-to diagnosis.
To estimate long term survival, health, and educational/social functioning in patients with Lyme neuroborreliosis compared with the general population.
To monitor epidemiological trends of infectious meningitis (bacterial and viral) and encephalitis in Denmark.
To examine clinical characteristics and outcome of patients with late diagnosis of community-acquired bacterial meningitis (CABM).
The purpose of this review is to give an overview of viral meningitis and then focus in on some of the areas of uncertainty in diagnostics, treatment and outcome.
The treatment of persistent symptoms attributed to Lyme disease remains controversial. We assessed whether longer-term antibiotic treatment of persistent symptoms attributed to Lyme disease leads to better outcomes than does shorter-term treatment.
To describe the clinical manifestations, cerebrospinal fluid (CSF) characteristics, imaging studies and prognostic factors of adverse clinical outcomes (ACO) among adults with herpes simplex virus (HSV) or varicella zoster virus (VZV) CNS infections.
Encephalitis continues to result in substantial morbidity and mortality worldwide. Advances in diagnosis and management have been limited, in part, by a lack of consensus on case definitions, standardized diagnostic approaches, and priorities for research.
Lyme borreliosis (Lyme disease) is caused by spirochaetes of the Borrelia burgdorferi sensu lato species complex, which are transmitted by ticks. The most common clinical manifestation is erythema migrans, which eventually resolves, even without antibiotic treatment. However, the infecting pathogen can spread to other tissues and organs, causing more severe manifestations that can involve a patient's skin, nervous system, joints, or heart. The incidence of this disease is increasing in many countries. Laboratory evidence of infection, mainly serology, is essential for diagnosis, except in the case of typical erythema migrans. Diagnosed cases are usually treated with antibiotics for 2-4 weeks and most patients make an uneventful recovery. No convincing evidence exists to support the use of antibiotics for longer than 4 weeks, or for the persistence of spirochaetes in adequately treated patients. Prevention is mainly accomplished by protecting against tick bites. There is no vaccine available for human beings.
Lyme borreliosis, caused by spirochaetes of the Borrelia burgdorferi genospecies complex, is the most commonly reported tick-borne infection in Europe and North America. The non-specific nature of many of its clinical manifestations presents a diagnostic challenge and concise case definitions are essential for its satisfactory management. Lyme borreliosis is very similar in Europe and North America but the greater variety of genospecies in Europe leads to some important differences in clinical presentation. These new case definitions for European Lyme borreliosis emphasise recognition of clinical manifestations supported by relevant laboratory criteria and may be used in a clinical setting and also for epidemiological investigations.
Mortality and morbidity rates are high among adults with acute bacterial meningitis, especially those with pneumococcal meningitis. In studies of bacterial meningitis in animals, adjuvant treatment with corticosteroids has beneficial effects.
Lyme disease is the most common vector-borne infection in some temperate regions of the Northern Hemisphere. However, for most areas of endemic disease reliable epidemiologic data are sparse.
Specialespecifikt kursus om immundefekt og feber af ukendt årsag
28.01.2020 - 29.01.2020
International Congress on Infectious Diseases (ICID) 2020
Kuala Lumpur, Malaysia
20.02.2020 - 23.02.2020
Dansk Selskab for Intern Medicin (DSIM) årsmøde og overrækkelse af Hagedorn prisen 2020
Novo Nordisk Fonden, Tuborg Havnevej 19, 2900 Hellerup
Conference on Retroviruses and Opportunistic Infections (CROI) 2020
Boston, Massachusetts, USA
8.03.2020 - 11.03.2020
Når CROI går i fisk - med transmissioner fra CROI 2020
10.03.2020 - 11.03.2020
Retningslinjer til sundhedsprofessionelle vedr. håndtering af infektion med zikavirus (2019)
Antiviral behandling af hiv smittede personer (2019)
Lumbalpunktur af patienter i blodfortyndende behandling (2019)
Single dose of Doxycycline for the prevention of TBRF
19.01.2020Clinical Infectious Diseases Advance Access
Characteristics of invasive pneumococcal disease (IPD) caused by emerging serotypes after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in England; prospective observational cohort study, 2014-18
19.01.2020Clinical Infectious Diseases Advance Access
The effect of therapeutic drug monitoring of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients: the DOLPHIN trial protocol of a multi-centre randomised controlled trial
17.01.2020Latest Results for BMC Infectious Diseases
Fatal hemorrhagic varicella in a patient with abdominal pain: a case report
17.01.2020Latest Results for BMC Infectious Diseases
Antifungal resistance in patients with Candidaemia: a retrospective cohort study
17.01.2020Latest Results for BMC Infectious Diseases
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