Sepsis meningitis malaria
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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

SEPSIS - MENINGITIS - MALARIA

Pr. B. Vandercam

Consultation Maladies Infectieuses et Tropicales

Cliniques Universitaires St-Luc

Octobre 2004


Sepsis

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

Working definitions associated with sepsis and related disorders


Source of infection

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


Sepsis meningitis malaria

  • 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

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


Sepsis meningitis malaria

  • 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

Results


Skin lesions and systemic infections

Skin lesions and systemic infections


Purpura fulminans treatment

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

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


Sepsis meningitis malaria

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

Asplenia

  • Overwhelming sepsis

  • Stand by therapy

    • Amoxi clav

    • Allergy, travel --> Moxifloxacin, Levofloxacin

    • Vaccination

  • Antibioprophylaxis


Asplenia sepsis

Asplenia sepsis

  • Infecting organisms

    • S. pneumoniae

    • H. influenzae

    • N. meningitidis

    • Capnocytophaga spp

  • Treatment

    • Ceftriaxone or Cefotaxime


Nosocomial sepsis immunocompetent adult

Nosocomial *sepsis - immunocompetent adult

  • Infecting organisms

    • Enterobacteriacae

    • S. aureus

    • Strep pneumoniae

    • Bacteroïdes spp

    • P. aeruginosa

    • CNS

      * readmission - nursing home


Nosocomial sepsis

Nosocomial sepsis

  • Local epidemiology

  • Colonization

  • Previous antibiotherapy

  • IV line

  • Urinary catheter

  • Invasive procedure


Treatment

Treatment

  • Vancomycin ?

  • Cefotaxime or Ceftriaxone or Pip/tazo

    + amino

  • Ceftazidime or Cefepime or Carbapenem + amino


Sepsis neutropenia

Sepsis neutropenia

  • Infecting organisms

    • Strepto spp

    • CNS

    • S. aureus

    • Enterobacteriacae

    • P. aeruginosa

  • Colonization

  • Previous antibiotherapy


Neutropenia low risk

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

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

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

Clinical diagnosis

  • Fever sensitivity 85%

  • Menigism70%

  • Altered mental status60%

  • Kernig

    Sensitivity 5%

    Specificity 95%

    Poser la question = y répondre


Case presentation

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

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

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

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

CSF characteristics in selected neurologic conditions


Sepsis meningitis malaria

  • 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

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

Antibiotherapy

  • Listeria : ampi or CTX

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

  • H. influ :  vaccination


Antibiotherapy dosage

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

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

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

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

Meningitis : HIV /AIDS

  • Infecting organisms

    • C. neoformans

    • S. pneumoniae

    • M. tuberculosis

    • L. monocytogenes

    • T. pallidum

    • N. meningitidis

    • HIV


Meningitis cerebrospinal fluid shunt

Meningitis : cerebrospinal fluid shunt

  • Infecting organisms

    • Coag neg staph

    • S. aureus

    • Diphteroids

    • Enterobacteriaceae

  • Treatment

    • Vancomycin + cefta


Meningitis after cranial or spinal trauma

Meningitis : after cranial or spinal trauma

  • Infecting organisms

    • S. pneumoniae

    • H. influ

  • Treatment

    • Cefotaxime or Ceftriaxone


Meningitis after cranial or spinal trauma 4 days

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

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

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


D lai d apparition de malaria selon esp ce

Délai d’apparition de malaria selon espèce

Schwartz NEJM 2003; 349, 1510


Malaria en belgique

Malaria en Belgique

Institut de Santé Publique-Louis Pasteur


Who dies from travelers malaria

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 fi vre au retour des tropiques est une malaria jusqu preuve du contraire

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


Contribution de certaines anomalies biologiques au diagnostic de la malaria

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 p falciparum

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)


Sepsis meningitis malaria

  • 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 p falciparum s v re

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


Sepsis meningitis malaria

+

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

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 treatment1

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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