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Microbiology

Infections

Question 77 of 77

A 72 year old patient presents to ED with a fever, headache and neck stiffness. You suspect meningitis. A lumbar puncture is performed and the results shown below. What is the most likely causative infective pathogen:

  • WCC: 840 cells x 106/L (neutrophil predominance)
  • Protein: markedly elevated
  • Glucose: 2.1 mmol/L (blood glucose 6 mmol/L)
  • Gram stain shows a Gram-positive diplococci

Answer:

The CSF analysis is characteristic of a bacterial meningitis. The most common causes of bacterial meningitis in this age group are Streptococcus pneumoniae (Gram-positive diplococci), Neisseria meningitidis (Gram-negative diplococci) and Listeria monocytogenes (Gram-positive rod).

Meningitis

Infective Agents

  • Viral causes
    • Enteroviruses (Coxsackievirus, poliovirus and Enterovirus)
    • Varicella zoster virus
    • Herpes simplex virus
    • Mumps virus
  • Bacterial causes vary by age:
Age Pathogens
Neonate (< 1 month) Group B Streptococcus, Escherichia coli, Listeria monocytogenes
Children (< 15 years) Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae
Adult (< 55 years) Streptococcus pneumoniae, Neisseria meningitidis
Adult (> 55 years) Streptococcus pneumoniae, Neisseria meningitidis, Listeria monocytogenes
Immunosuppressed Mycobacterium tuberculosis, Cryptococcus

Clinical Disease

  • Headache
  • Photophobia
  • Fever
  • Neck stiffness
  • Poor feeding/irritability
  • Altered consciousness or confusion
  • Kernig's sign (extension of flexed knee causes pain and resistance to movement)
  • Brudzinski's sign (passive neck flexion causes bilateral hip and knee flexion)
  • Bulging fontanelle

Diagnosis

  • Lumbar puncture for CSF analysis, Gram-stain, microscopy and culture
  • Blood for culture, rapid antigen detection and glucose determination
  • CT head to exclude encephalitis

CSF Interpretation

  • Physical characteristics
    • Opening pressure: normally 10 - 20 cm H2O, may be elevated in infection or bleed
    • Colour: clear and colourless is normal
    • Turbidity: cloudy or turbid CSF may indicate the presence of WBCs, RBCs, microorganisms or an increase in protein levels
    • Viscosity: ‘thick’ CSF may be seen in infection
  • Biochemistry
    • CSF glucose: usually about 2/3s that of serum glucose, may be decreased in bacterial or TB infection but usually remains normal in viral infection
    • CSF protein: increase in protein may be seen in infection
    • CSF lactic acid: usually raised in bacterial infection, but normal in viral infection
    • CSF lactate dehydrogenase (LDH): usually raised in bacterial infection, but low or normal in viral infection
    • CSF xanthochromia (bilirubin): seen following subarachnoid haemorrhage
  • Microscopy
    • CSF RBC count: presence of red blood cells may indicate bleeding into the CSF or a ‘traumatic tap’
    • CSF WBC count: raised in infection or inflammation of the CNS
    • CSF WBC differential: neutrophils increased in bacterial infection, an increase in lymphocytes with viral or TB infection
  • Microbiology
    • CSF Gram stain
    • CSF culture and sensitivity
    • CSF viral PCR testing
    • Other specific tests depending on which organisms are suspected
CSF Analysis Normal (adults) Bacterial Viral TB
Appearance Clear and colourless Turbid Normal Fibrin web
WCC (mm3) 0 - 5 High High High
Predominant cell type - Neutrophils Lymphocytes Lymphocytes
Glucose (mmol/L)

CSF:Serum Ratio

2.5 - 4.4 mmol/L

0.6

Low Normal Low
Protein (g/L) 0.2 - 0.4 High Normal or High High

Treatment

Infection Treatment
Initial empirical treatment for suspected meningitis
  • Benzylpenicillin should be given immediately if meningococcal disease is suspected in the community
  • In hospital, if aetiology unknown:
    • For child < 3 months, cefotaxime + amoxicillin
    • For adult and child 3 months - 50 years, ceftriaxone
    • For adult > 50 years, ceftriaxone + amoxicillin
    • Consider adding vancomycin if prolonged or multiple use of other antibacterials in the last 3 months, or if travelled, in the last 3 months, to areas outside the UK with highly penicillin- and cephalosporin-resistant pneumococci
Meningitis caused by Meningococci spp.
  • Benzylpenicillin or cefotaxime/ceftriaxone (suggested duration 7 days)
  • If penicillin allergic, chloramphenicol
Meningitis caused by Pneumococci spp.
  • Cefotaxime/ceftriaxone (suggested duration 14 days)
  • Consider adjunctive treatment with dexamethasone
  • If microorganism penicillin-sensitive, replace cefotaxime with benzylpenicillin
  • If microorganism highly penicillin and cephalosporin resistant, add vancomycin +/- rifampicin
Meningitis caused by Haemophilus influenzae
  • Cefotaxime/ceftriaxone (suggestive duration 10 days)
  • Consider adjunctive treatment with dexamethasone
  • If penicillin allergic or microorganism resistant to cefotaxime, chloramphenicol
  • For H. influenzae type b give rifampicin for 4 days before hospital discharge to those under 10 years of age or to those in contact with vulnerable household contacts
Meningitis caused by Listeria
  • Amoxicillin (or ampicillin) + gentamicin (suggested duration of treatment 21 days)
  • If penicillin allergic, co-trimoxazole

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  • Biochemistry
  • Blood Gases
  • Haematology
Biochemistry Normal Value
Sodium 135 – 145 mmol/l
Potassium 3.0 – 4.5 mmol/l
Urea 2.5 – 7.5 mmol/l
Glucose 3.5 – 5.0 mmol/l
Creatinine 35 – 135 μmol/l
Alanine Aminotransferase (ALT) 5 – 35 U/l
Gamma-glutamyl Transferase (GGT) < 65 U/l
Alkaline Phosphatase (ALP) 30 – 135 U/l
Aspartate Aminotransferase (AST) < 40 U/l
Total Protein 60 – 80 g/l
Albumin 35 – 50 g/l
Globulin 2.4 – 3.5 g/dl
Amylase < 70 U/l
Total Bilirubin 3 – 17 μmol/l
Calcium 2.1 – 2.5 mmol/l
Chloride 95 – 105 mmol/l
Phosphate 0.8 – 1.4 mmol/l
Haematology Normal Value
Haemoglobin 11.5 – 16.6 g/dl
White Blood Cells 4.0 – 11.0 x 109/l
Platelets 150 – 450 x 109/l
MCV 80 – 96 fl
MCHC 32 – 36 g/dl
Neutrophils 2.0 – 7.5 x 109/l
Lymphocytes 1.5 – 4.0 x 109/l
Monocytes 0.3 – 1.0 x 109/l
Eosinophils 0.1 – 0.5 x 109/l
Basophils < 0.2 x 109/l
Reticulocytes < 2%
Haematocrit 0.35 – 0.49
Red Cell Distribution Width 11 – 15%
Blood Gases Normal Value
pH 7.35 – 7.45
pO2 11 – 14 kPa
pCO2 4.5 – 6.0 kPa
Base Excess -2 – +2 mmol/l
Bicarbonate 24 – 30 mmol/l
Lactate < 2 mmol/l
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