ACUTE MENINGITIS: Diagnose en behandeling

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1 ACUTE MENINGITIS: Diagnose en behandeling Wesley Appermans-Béatrice Santens Onder supervisie van Prof. W. Meersseman Organism Site of entry Age range Predisposing conditions Neisseria meningitidis Nasopharynx All ages Usually none, rarely complement deficiency All conditions that predispose to Streptococcus pneumoniae pneumococcal bacteremia, Nasopharynx, direct extension fracture of cribriform plate, across skull fracture, or from All ages cochlear implants, cerebrospinal contiguous or distant foci of fluid otorrhea from basilar skull infection fracture, defects of the ear ossicle (Mondini defect) Listeria monocytogenes Gastrointestinal tract, placenta Older adults and neonates Defects in cell-mediated immunity (eg, glucocorticoids, transplantation [especially renal transplantation]), pregnancy, liver disease, alcoholism, malignancy Surgery and foreign body, Coagulase-negative staphylococci Foreign body All ages especially ventricular drains Endocarditis, surgery and foreign Staphylococcus aureus Bacteremia, foreign body, skin All ages body, especially ventricular drains; cellulitis, decubitus ulcer Gram-negative bacilli Various Older adults and neonates Advanced medical illness, neurosurgery, ventricular drains, disseminated strongyloidiasis Haemophilus influenzae Nasopharynx, contiguous spread from local infection Adults; infants and children if not vaccinated Diminished humoral immunity TABLE OF CONTENTS 1. Definition 2. Incidence 3. Signs and symptoms 4. Meningococcal vs pneumococcal meningitis 5. Interpretation cerebrospinal fluid 6. CT prior to LP 7. Use of corticosteroids 8. Antibiotic therapy 2. INCIDENCE 1,2 millioncases worldwide (1) USA (2) : 2.00 cases per 100,000 population (95% CI, 1.85 to 2.15) Case fatality rate 15,7% : 1.38 cases per 100,000 population (95% CI 1.27 to 1.50) Case fatality rate 14.3% (P=0.50). 18 to 34 years 0.66 cases per 100,000 population 35 to 49 years 0.95 cases per 100,000 population 50 to 64 years 1.73 cases per 100,000 population 65 years 1.92 cases per 100,000 population Reduction of incidence of 31% Case fatality 17,8% Pneumococcal 10,1% meningococcal 7% H influenza 18,1% L monocytogenes 9. Profylaxis 10. Reporting Health Care 11. Cases 12. Take home messages Netherlands (3) : 1,72 cases per 100,000 population : 0,94 cases per 100,000 population Case fatality 17% 18% pnemococcal 3% meningococcal 35% in L monocytogenes 1. DEFINITION Acute < 5 days Viral bacterial Subacute > 5 days / chronic Tbc Mycose Pathogens Community acquired Healthcare associated USA (2) S pneumoniae 71% N meningitidis 12% Group B strep 7% H influenzae 6% L monocytogenes 4% Evolution to meningitis in (4) 4% of invasive pneuumococcal infections 48% of invasive? Meningitidis infections 30% of invasive listeriosis 10% of invasive H influenzae infections 4% of invasive group B streptococcal infections 1

2 Netherlands (3) S pneumoniae 72% N meningitidis 11% Serogroup B 82% L monocytogenes 5% H influenzae 3% Other strepococcal sp 5% other Treponema pallidum Borrelia burgdorferi Cryptococcus neoformans Coccidioides immitis Tuberculosis S aureus 1% Drug-induced = emergency Mortality aseptic meningitis Absence of gram-staining Viral (Enterovirus) Other (mycobacteria, funghi, spirochetes) Medication (Malignancy) Symptomatology comparable, however self-limiting 3. SIGNS AND SYMPTOMS TRIADE (3) (41%) Fever (74%) Alterated mental state (71%) Nuchalrigidity / neckstifness (74%) Headache (83%) Nausea (62%) Photofobia Rash(8%) Classic triad (fever, neck stiffness, altered mental state or headache) 50-95% present (partially or fully) 40-45% sensitivity in bacterial meningitis diangnosis (4) Intracranial hypertension, skin rash, neurologic deficit less common (less usefull) (4) In eldery: confusion Viral meningitis Enteroviruses, HSV(-2), HIV, WNV, VZV, mumps LP: wbc <250/µL, protein <150mg/dL, normal glucose, PCR 4. PNEUMOCOCCAL VERSUS MENINGOCOCCAL MENINGITIS Pneumococcal meningitis Triade in 58% of patients (5) Mortality 17% (2) Meningococcal meningitis: meningitis and/or sepsis Triade in 27% + rash, myalgia (6) leg pain, cold hands and feet, and abnormal skin color Absence of focality Rash, shock (+- Waterhouse Friedrichson), DIC, Purpura fulminans Mortality 10 to 15 percent despite antibiotic treatment (2) (7) 2

3 5. CEREBRO SPINAL FLUID (CSF) CSF should be sent for: Cell count and differential Glucose concentration Protein concentration Gram stain and bacterial culture depending upon the level of concern for other etiologies of meningitis or meningoencephalitis Traumatic lumbar puncture / intracerebral or subarachnoid hemorrhage WBC / RBC into subarachnoid space Adjusted WBC count : to subtract one WBC for every 500 to 1500 red blood cells (RBCs) measured in the CSF. Xanthogromia : ddtraumatic LP ddsab CSF abnormalities : CAVE early presentation recent prior antimicrobial therapy neutropenia. Lumbarpuncture Normal CSF pressure : mmh2o Obese patients : up tot 250 mmh20 Infection, bleeding or tumor : balance between CSF secretion and reabsorption intracranial hypertension Complications: Brain herniation <5% WBC counts (/mm3) Normal clear acellular < 5 (0-4) (< 5 RBC) Bacterial cloudy > Formula Glucose Protein (mg/dl) (mg/l) (glccsf/serum) Normal (>0.6) < 500 < 4 > 75-80% PMN <40 (<0.4) > > 4 TBC Cloudy lymfo Fungal blurred Neutro Viral clear < 500 lymfo Aseptic clear Normal Lactate CSF Other tests Rapid tests (9) Latex agglutination tests : AG of common meningeal pathogens in the CSF do not appear to modify the decision to administer antimicrobial therapy NB false-positive results have been reported sensitivity is 95 to 100 percent Multiplex PCR <2 h Sensitivity and specificity in % Contribution in emergency diagnosis should be clarified Listeria monocytesis pleiocytosis 100 % PMN to 100% mononucl > 25% lymfo <40 (<0.4) elevated Every patient with suspected meningitis should have CSF obtained unless lumbar puncture (LP) is contraindicated. Gram staining suspicion of bacterial meningitis : bacterial etiology one day or more before culture results are known Gram-positive diplococci : pneumococcal infection Gram-negative diplococci : meningococcal infection Small pleomorphic gram-negative coccobacilli : Haemophilus influenzae infection Gram-positive rods and coccobacilli : Listerial infection Sensitivity: 60-90% 6. CT PRIOR TO LP head CT should be performed before LP -one or more of the following risk factors (10) 1. Immunocompromised state (eg, HIV infection, immunosuppressive therapy, solid organ or hematopoietic cell transplantation) 2. History of central nervous system (CNS) disease (mass lesion, stroke, or focal infection) 3. New-onset seizure (within one week of presentation) 4. Papilledema 5. Abnormal level of consciousness 6. Focal neurologic deficit 7. GCS <11 (11) Specificity: 100% CT : LP is contraindicated therapy for bacterial meningitis should be continued (if indicated) or evaluation and treatment for an alternative diagnosis should be undertaken. Imaging should not delay antibiotic therapy Mortality increases by 13% for every hour without antibiotics (11) 3

4 7.COMPLICATIONS OF BACTERIAL MENINGITIS (12) SYSTEMIC DIC MOF ARDS Septic or reactive artritis NEUROLOGICAL Impaired mental status Increased intracranial pressure and cerebral edema Seizures Focal neurologic deficits (eg, cranial nerve palsy, hemiparesis) Cerebrovascular abnormalities Sensorineural hearing loss Intellectual impairment Adolescents andadults Adults >50y, immunocompromised patients After head trauma After neurosurgery/csfdrainage N meningitidis, S pneumoniae (H. influenzae and group B Streptococcus ) S pneumoniae, N meningitidis, L monocytogenes S aureus, G-bacillae, H influenzae, S pneumoniae S Aureus, coagulasenegativestaf, G-bacillae, P aeruginosa ceftriaxone 2x2g IV or cefotaxime 6x2g IV ceftriaxone 2x2g IV or cefotaxime 6x2g IV PLUS Amoxicilline 6x2g IV or cotrimoxazole 4x160/800mg IV Beta-lacta allergy: vancomycin+ moxifloxacin 1x400mg IV ceftriaxone 2x2gIV or cefotaxime 6x2g IV ceftazidime 3x2gIV PLUS vancomycin2x1g IV Empiric therapy according to Antibioticagids.be Fig. I. Making decisionson clinical parameters andcsf Neurological sequelae occur in 5-40% of patients (13) to diminish rate of complications 8. USE OF CORTICO- STEROIDS Unfavourable outcome (3) 10mg dexamethasone 4x/d, 4 days34% vs 41% (p<0,0001) Unfavourable outcome OR 0,54 Death OR 0,46 Hearing loss OR 1,32, (p 0,3) Cochrane review (13) non-significant reduction in mortality (17.8% versus 19.9%; risk ratio (RR) 0.90, 95% confidence interval (CI) 0.80 to 1.01, P value = 0.07 reducedmortality in Streptococcus pneumoniae(s. pneumoniae) meningitis (RR 0.84, 95% CI 0.72 to 0.98 lower rates of severe hearing loss (RR 0.67, 95% CI 0.51 to 0.88), any hearing loss (RR 0.74, 95% CI 0.63 to 0.87) and neurological sequelae (RR 0.83, 95% CI 0.69 to 1.00). severe hearing loss in children with H. influenzaemeningitis (RR 0.34, 95% CI 0.20 to 0.59) 9. ANTIBIOTIC TREATMENT Treatment should be initiatedas soon as possible Prognostic markers: hypotension, altered mental status and seizures (14) Prediction of risk: Low (0): 9% adverse outcome (death or neurologic deficit ) Intermediate (1): 33% adverse outcome High (2-3): 56% adverse outcome Additional risk factor: advancement TREATMENT OF ACUTE MENINGITIS 1. Antibiotic therapy 2. Encefalitis Iv aciclovir10 mg/kg / 8u (3x/d) HSV PCR 3. Use of corticosteroids Dexamethasone IV 10 mg/ 6u 4 days (4x/d) In association with antibiotics 4

5 Health care associated(16) After 48 hours of hospitalisation until7 days after release Different spectrum of microorganisms Craniotomy 0,8-1,5%, Ventricular or lumbar catheters 8 / 5% head trauma 1,4% LP 1/ PROFYLAXIS 3. Timing of prophylaxis secondary disease : highest immediately after the onset of disease in the index patient. within 10 days of the primary case as early as possible ( <24 ) 4. Anitmicrobial profylaxis Rifampicin : 2d 2x600 mg PO Ciprofloxacine : 1x 500 mg PO Ceftriaxone : 1x 250 mg I.M. Azithromycin is not recommended as a first-line agent for chemoprophylaxis. Act-Hib Meningitec (2002) Health care associated Prevention - Vaccination Prevenar 13, Pneumovax 23 PCV7 2006, PCV No serotype replacement of non vaccine serotypes (Netherlands (4)) Incidencenon PVC7-serotypes increasedby 61% 95% CI 54-69) 1. What? index case Invasive infection PROFYLAXIS use of droplet precautions be continued for 24 hours after institution of effective antibiotics in patients with suspected or confirmed N. meningitidis infection [2 2. Whom to treat? Close contacts as early as possible (>8 hours) contact directly exposed to the patient's oral secretions 7days before the onset until 24 hours after initiation of appropriate antibiotic therapy [2]. Prevention Vaccination (17) Introduction of PCV7 in 2000 in USA Decreased incidence PM 64% in children <2y, 54% >65y Introduction of PCV13 in 2010 in USA DecreasedincidencePM 39% from2008 to2014 Fatalityratewas not affected Prophylaxis is not indicated if exposure to the index case is brief. ex. healthcare workers <-> direct exposure to respiratory secretions 5

6 10. REPORTING HEALTH CARE CASUS 1 v, 17 Jaar Medische voorgeschiedenis blanco Presentatie e maal braken Deze nacht ziek geweest, overdag niet naar school geweest. gebraakt hevige hoofdpijn in ambulance ingedaald bewustzijn slecht reagerend op prikkels Bij aankomst op spoed niet meer responsief indalend bewustzijn. Ontstaan van rash op onderbenen. Geen reizen Voordien niet ziek geweest Therapie bij opname nihil REPORTING HEALTH CARE Klinisch onderzoek Ligt met de ogen open, kijkt niet aan. Spreekt niet, voert geen opdrachten uit. 3 vingers nekstijf. Pupillen eerder mydriatisch, slechts discreet lichtreactief. Geen terugtrekreactie op pijn in de 4 LM. Bij testing nekstijf grijpt pte naar nek/hoofd. VZR bilateraal in flexie. Petechiën thvol > BL. 11. CASUSSEN En dan nu, Praktische voorbeelden Eerste labo én hemoculturen onmiddellijk gestart met triple therapie na afname van hemoculturen Rocephine 2x2gIV Zovirax 3x10mg/kg/d Dexamethasone 4x10mg/d Na toediening van medicatie: CT Intubatie Oplijnen LP 6

7 Zeer snelle evolutie bilateraal mydriatische pupillen afwezigheid van hersenstamreflexen controle CT schedel : lichte toename van het cerebrale oedeem toonde. NCH : infauste prognose Geen ventriculo-externe drainage Hersendood Na overleg met ouders, screening voor orgaandonor Prelevatie van de organen werd uitgevoerd na 48 uur antibiotische behandeling. Lumbaal punctie: CASUS 2, M 67 j Medischevoorgeschiedenis Operatie meniscus rechts Genitale HSV 2 Presentatie op speodgevallen 16/04: continue, drukkende pijn in de bovenbuik gekregen Bandvormige pijn Bij stappen superponerende pijn. Geen vomitus of nausea. Geen diarree. Heeft sinds deze middag ook last van hoofdpijn, nu nog aanwezig. parietaal continue zeurende pijn. Geen fotofobie of sonofobie. Deze middag 2x400mg brufen genomen zonder effect Geen koorts gemaakt. Geen spierpijn. Geen rillingen. Geen zieken in de omgeving. Verdere systeemanamnese negatief Thuistherapie bij opname geen CT hersenen: 16/03 Normaal hersenparenchym. Geen verschuiving van de middellijn. Beperkte vernauwing van de voorhoornen van beide laterale ventrikels en de temporale hoornen. Bewaarde witgrijze stof differentiatie. Geen intra-craniëlebloeding. Geen evidentie voor cerebrale massa. CT hersenen herevaluatie: 17/03 9u Verdere verstrijking vd sulci en iets nauwer kaliber vd laterale ventrikels ikvlichte toename vhhersenoedeem. Geen obliteratie vdbasale cisternen. Geen tonsillaireinklemming Bewaarde witgrijze stof differentiatie. Geen intracraniële bloeding / abces / verweking. Klinisch onderzoek : Parameters: Bloeddruk (mmhg): 161/81 Pols (/min): 87 T 37.2 C AHfreq 16/min O2sat 97% Alg: helder en adequaat Hartauscultatie: RR, S1S2, geen souffle Longauscultatie: Zuiver VAG, geen bijgeluiden Abdomen: normoperistalsis, wisselend tympaan, soepel, geen drukpijn, geen hepatosplenomegalie, Murphy - Drukpijn basale ribben, erger bij rechtkomen Geen malleolaire oedemen, licht gestuwde CVD, HJR - Geen NSP, geen WSP Neuro: craniale zenuwen ok, bewaarde kracht en sensibiliteit in BL, Barre -, Mingazinni Echo abdomen: Gevorderde leversteatose. Geen argumenten voor pancreatitis met enige reserve gezien zeer beperkte sensitiviteit van echografie in de detectie van pancreatitis. Geen intra-abdominale infectiefocus aantoonbaar. 1/ Gevorderde leversteatose. BESLUIT: wandpijn en forse leversteatose, op basis van anamnese vermoedelijk alcoholisch 7

8 Op 17/04: opnieuw presentatie op spoedgevallen toegenomen hoofdpijnklachten : 8x ibuprofen hebben ingenomen, zonder enige beterschap. vertraagde respons volgens echtgenote Holocranieel niet bandvormig, niet kloppend, eerder zeuren Er is mogelijks lichte fotofobie maar geen sonofobie Geen koorts Geen misselijkheid, geen braken. Klinisch onderzoek: idem Neuro: geen uitvalverschijnselen, geen lateralisatie, terminaal nekstijf Behandeling? Geen beeld van encefalitis noch myelitis immuuncompetent antivirale therapie ter behandeling van een postprimaire HSV 2 meningitis? Hier vrij uitgesproken beeld: start anti-viraletherapie (IV Zovirax 10mg/kg, 3 keer per dag) 7-10 dagen. Cave weinig literatuur over, evidence based? NB : Circa 20-30% van patiënten met genitale herpes zullen één of meerdere episoden van (een subklinische tot licht symptomatische) virale meningitis doormaken. 12. TAKE HOME MESSAGES 1. Community-acquired healthcare associated 2. Pneumococcal meningococcal 3. Triade not alwayspresent 4. Empiric antibiotics asapafter CSF analysis 5. Corticosteroids reduce neurologic sequelae REFERENCES (1) Pathophysiologyof bacterialmeningitis: mechanism(s) ofneuronalinjury. ScheldWM, KoedelU, NathanB, Pfister HWJInfect Dis. 2002;186Suppl2:S225. (2) Bacterial meningitis in the United States, Thigpen MC, Whitney CG, Messonnier NE, Zell ER, LynfieldR, Hadler JL, Harrison LH, FarleyMM, ReingoldA, Bennett NM, Craig AS, Schaffner W, Thomas A, LewisMM,Scallan E,Schuchat A, Emerging Infections Programs Network NEnglJMed. 2011;364(21):2016. (3) Community-acquired bacterial meningitis in adults in the Netherlands, : a prospective cohort study.aubijlsma MW, Brouwer MC, Kasanmoentalib ES, Kloek AT, Lucas MJ, Tanck MW, van der Ende A, vandebeek DSOLancet Infect Dis. 2016Mar;16(3): Epub2015Dec1. (4) Clinicaldecision rules for acutebacterial menigitis : current insights Clinical presentation varies according to several factors: age, duration, evolution of symptoms at time of clinical examination (5) Clinical features and prognostic factors in adults with bacterial meningitis. van de Beek D, de Gans J, Spanjaard L,Weisfelt M, Reitsma JB, Vermeulen M N Engl J Med. 2004;351(18):1849. (6) Clinical features, outcome, and meningococcal genotype in 258 adults with meningococcal meningitis: a prospective cohort study. Heckenberg SG, de Gans J, Brouwer MC, Weisfelt M, Piet JR, Spanjaard L, van der EndeA, vandebeek DMedicine (Baltimore). 2008;87(4):185. (7) Population-based analysis of meningococcal disease mortality in the United States: Sharip A, SorvilloF, Redelings MD, MascolaL,Wise M,Nguyen DM Pediatr Infect DisJ. 2006;25(3):191. (8) Medical microbiology: laboratory diagnosis of invasive pneumococcal disease.auwerno AM, Murdoch DRSOClinInfect Dis. 2008;46(6):926. (9) Computedtomography ofthe head beforelumbar punctureinadultswithsuspected meningitis.auhasbun R,Abrahams J,Jekel J,Quagliarello VJSON EnglJMed. 2001;345(24):1727., (10) clinicaldecision rules foracute bacterial meningitis: current insights (11) Spectrum of complications during bacterial meningitis in adults. Results of a prospective clinical study.aupfister HW, FeidenW, Einhäupl KMSOArch Neurol. 1993;50(6):575. (14)AnnIntern Med. 1998Dec1;129(11): Community-acquired bacterial meningitis: risk stratification for adverse clinical outcome and effect of antibiotictiming.aronin Sl, peduzzi o, quagliarello VG (16) Nosocomial Bacterial Meningitis Diederik van de Beek, M.D., Ph.D., James M. Drake, M.B., B.Ch., and Allan R.Tunkel, M.D.,Ph.D. N Engl J Med 2010; 362: January 14, 2010DOI: /NEJMra

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