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SEPSIS - MENINGITIS - MALARIA. Pr. B. Vandercam Consultation Maladies Infectieuses et Tropicales Cliniques Universitaires St-Luc Octobre 2004 . Sepsis. Focus Absence of focus Purpura fulminans Community acquired sepsis immunocompentent adult Nosocomial sepsis immunocompetent adult

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SEPSIS - MENINGITIS - MALARIA

Pr. B. Vandercam

Consultation Maladies Infectieuses et Tropicales

Cliniques Universitaires St-Luc

Octobre 2004


Sepsis

  • Focus

  • Absence of focus

    • Purpura fulminans

    • Community acquired sepsis immunocompentent adult

    • Nosocomial sepsis immunocompetent adult

    • IV DU

    • Asplenic (anatomic or functional)

    • Neutropenia

    • Toxic shock syndrome


Working definitions associated with sepsis and related disorders


Source of infection

  • Anamnesis (pets, travel, household, …)

  • Physical examination (purpura, scar …)

  • Blood culture

    Urine culture

    RX thorax

    Echo (scan abdo) obstacle abscess collection

    Echo cardio


  • Activated protein C (- 6 %)

  • Corticosteroids (low (HC 200-300 mg/day) - long (5-7d))

  • Intensive insuline therapy (- 17%)

  • Volume resuscitation (- 15%)


Prior medicare database analyses

  • MEEHAN T. Jama 1997; 278:2080 Mortality increased significantly with delay in first Abx dose > 8 hrs (registration to dose)

  • GLEASON PP. Arch Intern Med 1999, 159:2562 Mortality based on abx (OR)

    Cephalosporin 1.0

    Cephalosporin + mac 0.76

    Fluoroquinolone0.64


  • Method : review of Medicare database for patients > 65 yrs hospitalized with x-ray confirmed CAP

  • Period reviewed : July ’98 - March ’99

  • Patients : 13 771

  • PSI score : III - 47 % IV - 24 %


Results


Skin lesions and systemic infections


Purpura fulminans : treatment

  • Cefotaxime 2 gr q 4 - 6 h

    or Ceftriaxone 2 gr q 12 h

  • Allergy

    Vanco 1 gr q 12 h + Aztreonam 2 gr q 6 h or Moxifloxacin 0,4 gr q 24 h or Levofloxacin 0,5 gr q 12 h


Community acquired sepsis - immunocompetent adults

  • Infecting organisms

    • Enterobacteriacae

    • Staph aureus

    • Strept pneumoniae & spp

    • N. meningitidis

    • Bacteroides spp

  • Treatment

    • Cefotaxime or Ceftriaxone

    • Amoxi clav or cefurox + amino


IVDU

  • Infecting organisms

    • Staph aureus

  • Exclude endocarditis

  • Previous antibiotherapy

  • Treatment

    Oxacilline 2 gr q 6 h or Vancomycine 1 gr q 12h +

    Genta 2,5 mg/kg q 12 h


Asplenia

  • Overwhelming sepsis

  • Stand by therapy

    • Amoxi clav

    • Allergy, travel --> Moxifloxacin, Levofloxacin

    • Vaccination

  • Antibioprophylaxis


Asplenia sepsis

  • Infecting organisms

    • S. pneumoniae

    • H. influenzae

    • N. meningitidis

    • Capnocytophaga spp

  • Treatment

    • Ceftriaxone or Cefotaxime


Nosocomial *sepsis - immunocompetent adult

  • Infecting organisms

    • Enterobacteriacae

    • S. aureus

    • Strep pneumoniae

    • Bacteroïdes spp

    • P. aeruginosa

    • CNS

      * readmission - nursing home


Nosocomial sepsis

  • Local epidemiology

  • Colonization

  • Previous antibiotherapy

  • IV line

  • Urinary catheter

  • Invasive procedure


Treatment

  • Vancomycin ?

  • Cefotaxime or Ceftriaxone or Pip/tazo

    + amino

  • Ceftazidime or Cefepime or Carbapenem + amino


Sepsis neutropenia

  • Infecting organisms

    • Strepto spp

    • CNS

    • S. aureus

    • Enterobacteriacae

    • P. aeruginosa

  • Colonization

  • Previous antibiotherapy


Neutropenia « Low risk »

Amoxi clav 2 gr q 6-8 h +

Cipro 750 q 12 h OR

Ceftriaxone 2 gr q 12 h +

Amikacin 15-25 mg/kg q 24 h


Neutropenia « High risk »

  • Ceftazidime 2 gr q 8 h

  • Cefepime 2 gr q 8 h

  • Pip/tazo 4 gr q 6 h

  • Imipenem 750 mg q 6 h

  • Meropenem 2 gr q 8 h

    + amino ???


Toxic shock syndrome

  • Infecting organisms

    • Strepto A, B, C,

    • Staph aureus

  • Treatment

    • Cefazoline 2 gr q 8 h + Clindamycine 600 mg q 8 h


Clinical diagnosis

  • Fever sensitivity 85%

  • Menigism70%

  • Altered mental status60%

  • Kernig

    Sensitivity 5%

    Specificity 95%

    Poser la question = y répondre


Case presentation

  • 25-year-old man

  • 2-day history of severe headache, fever, neck stiffness

  • 38,3 °C

  • No rash

  • Normal mental status and neurologic examination

  • Pain on neck flexion but able to flex his neck fully

  • No Kernig and Brudzinski signs


Contraindications of lumbar puncture

  • Known or suspected space-occupying lesions with mass effect

     LP deferred until CT scan

  • Severe uncorrected coagulopathy (INR > 1.5)

  • Trombocytopenia (platelet count < 50 000/mm³)

  • Infection at the puncture site (decubitus ulcer)

    - Glasgow < 13

    - Shock


When should a computerized tomography scan precede a lumbar puncture ?

  • Age over 60 years

  • Immunocompromised state

  • History of primary neurologic disease, head trauma, neurosurgery

  • History of seizure within the past week

  • Altered mental status, cilated or poorly reactive pupils, occular palsy and focal neurologic abnormalities

  • Papilledema, bradycardia, irregular respiration

  • History of cancer

  • Suspicion of brain abscess (endocarditis, bacteremia …)

    Empiric anti infective therapy without delay


CSF examination

  • Gram stain - Ziehl - Ink

  • Culture (bacteria, fungi, brucella, nocardia …)

  • Bacterial antigens

    • if antibiotherapy

    • Gram or culture negative

  • PCR virus + BK

  • Blood culture 60 % + in acute bacterial meningitis


CSF characteristics in selected neurologic conditions


  • Purpura, petechia  N. meningitidis

  • Cellulitis face  S. aureus

    H. influ

  • VRS, VRI  S. pneumoniae

    H. influ

  • Parotitis  Mumps

  • Endocarditis  S. aureus

  • Septic arthritis  S. pneumoniae S. aureus

  • Pregnancy  Listeria


Acute meningitis treatment

  • IV line - blood cultures

  • AB + dexa 10 mg within 30 min(*)

  • LP if no contraindication

  • Chest x-ray

  • Delta scan if needed

    (*) S. pneumoniae : 4 h

    N. meningitidis : 2 h LCR


Antibiotherapy

  • Listeria : ampi or CTX

  • S. pneumoniae : peni i 10% cef 3 i 1%

  • H. influ :  vaccination


Antibiotherapy dosage

Penetration - bactericide - CMI

  • Cefotax 2 gr -(4 gr) q 4h (ratio 25%)

  • Ceftriaxone 2 gr q 12h (ratio 15 - 30%)

  • Ampi 2 gr q 4h (ratio 10 - 15%)

  • Cefepime (ratio 10%)

  • Ceftazidime (ratio 20 - 40%)

  • Cotrimoxazole (ratio 30 - 35%)


Antibiotic therapy in meningitis

  • IV from the beginning to the end …

  • Standard therapy

    • 7 days for N. meningitidis

    • 10 - 14 days for S. pneumoniae

    • (14) - 21 days for L. monocytogenes


Meningitis : child > 3 months - adults < 50 yrs

  • Infecting organisms

    • S. pneumoniae

    • N. meningitidis

    • H. influ

    • L. monocytogenes

  • Treatment

    • Cefotaxime + ampicilline

    • Ceftriaxone + ampicilline


Meningitis : alcoohol - adults < 50 yrs Cellular immune deficiency - Debilitating illness

  • Infecting organisms

    • S. pneumoniae

    • L. monocytogenes

    • N. meningitidis

    • Gram negative bacilli

  • Treatment

    • Cefotaxime + ampicilline

    • Ceftriaxone + ampicilline


Meningitis : HIV /AIDS

  • Infecting organisms

    • C. neoformans

    • S. pneumoniae

    • M. tuberculosis

    • L. monocytogenes

    • T. pallidum

    • N. meningitidis

    • HIV


Meningitis : cerebrospinal fluid shunt

  • Infecting organisms

    • Coag neg staph

    • S. aureus

    • Diphteroids

    • Enterobacteriaceae

  • Treatment

    • Vancomycin + cefta


Meningitis : after cranial or spinal trauma

  • Infecting organisms

    • S. pneumoniae

    • H. influ

  • Treatment

    • Cefotaxime or Ceftriaxone


Meningitis after cranial or spinal trauma (> 4 days)

  • Infecting organisms

    • Enterobacteriaceae

    • S. aureus

    • P. aeruginosa

    • S. pneumoniae

  • Treatment

    • Vancomycin + ceftazidime


People on the move: demographics year 2003

  • 175 million persons live outside of their country of origin (2,9%) of the world's population

  • Population of concern to UNHCR: 21,6 million

  • Refugees 11,7 million

  • Internally displaced persons: 20-30 million

  • Rural to urban migration: 20-30 million/year

  • 1-2 million migrate permanently every year

  • 700 million tourist arrivals/year


Malaria risk pyramid for 1 month of travel without chemoprophylaxis

  • Oceania1:5

  • Africa1:50

  • South Asia1:250

  • Southeast Asia1:2500

  • South America1:5000

  • Mexico and Central America 1:10 000

01643


Délai d’apparition de malaria selon espèce

Schwartz NEJM 2003; 349, 1510


Malaria en Belgique

Institut de Santé Publique-Louis Pasteur


Who dies from travelers’ malaria ?

USA & Canada (n = 21) Total (%)

No chemo 21 100

Dealy seeking care 1 5

Missed by MD 13 62

Lab misdiagnosis 9 43

Mistreatment11 52

MMWR July 20, 2001 & 1999; 48:SS-1 Kain K et al. CMAJ 2001, 164:654-659


Toute fièvre au retour des tropiques est une malaria jusqu’à preuve du contraire !!


Contribution de certaines anomalies biologiques au diagnostic de la malaria

  • Thrombopénie : 60-85%

    Si de plus GB  N : VPP : 77%VPN : 92%

  • Leucopénie ou GB N : quasi-constante

  • CRP: 100% (mais très peu spécifique)

    Précoce

    Très élevé // à parasitémie et à évolution

     VPN très bonne (probable) si CRP N

  •  LDH :(très) sensible : 83-100%

    peu spécifique : 60%

  •  haptoglobine :  90% des cas

    VPN élevée de taux N

    Intérêt potentiel couplé à CRP


Malaria à P. falciparum

Règles: Vu la provenance essentiellement africaine des souches isolées en Belgique

Hospitaliser si:

  • patient non immun

  • patient immun avec > 2% GR+ et/ou critères de gravité

    Préférer un traitement à base de quinine (5j ± 2j)si malaria sévère(+ doxycycline)


  • La parasitémie peut augmenter durant les premières 24h de traitement

    (action sur points limités du cycle qui continue à évoluer "malgré" le traitement)

     Résistance R3 est déterminée à 48h (où diminution de 75% doit être obtenue)

  • La température peut persister pendant 72-96h sans signification péjorative

  • Si haute suspicion de malaria, et GE (-) :

    répéter 3 - 4 x sur 48h


Traitement de la malaria à P. falciparum sévère

  • Bihydrochlorate de quinine

    • 500 mg IV (dans 250ml glucosé ED) en 4h/ 3x/j pdt 3-7j

    • 10 mg/kg (soit 8mg/kg de quinine base) 3x/j chez enfant

      N.B.: si origine S. Est Asiatique (ou si malaria sévère ?)

      dose charge : 20 mg/kg (donc 1 seule fois)

      ou (dès que possible/début si pas V /peu critères gravité)

  • Sulfate de quinine: 500 mg per os 3x/j pdt 3-7 jours


+

Doxycycline 200 mg/j puis 100 mg/j pdt 6 j

ou

Clindamycine 600 mg 3-4x/jour pdt 3-7 j

(par exemple, si grossesse)


Malaria treatment

P. falciparum (zone A) - P. vivax, P. ovale (*)

  • Day 1 : nivaquine 600 mg + 300 mg

  • Day 2 : 300 mg

  • Day 3 : 300 mg

    (*) Primaquine 15 mg q 24 h x 14 days


Malaria treatment

P. falciparum

  • Malarone P.O 4 x 3 days (food, milky drink)

  • Quinine sulfate 500 mg q 8 h x 3-7 days

    + Doxy 100 mg q 12h x 7 days

  • Quinine I.V. 10-20 mg/kg over 4 h in 5% dextrose

    Quinine I.V. 10 mg/kg over 4 h q 8 h

    + Doxy 100 mg q 12h or Clinda 10 mg/kg q 8h

  • Qt ! Halofantrine ! Mefloquine 2 weeks


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