Question 21.1

A 75-year-old male with chronic lymphocytic leukaemia (CLL) presents with a 4-day history of fever,
headache and neck stiffness.

On examination, his temperature is 39°C, with a Glasgow Coma Score of E3M6V4 and a positive Kemig's sign. There are no focal neurological signs.

Cerebrospinal fluid results are shown below:

Parameter	Patient Value	Adult Normal Range
Opening Pressure	24 cmH2O	12 – 25
Total protein	1.20 g/L*	0.15 – 0.45
Glucose	1.2 mmol/L*	3.3 – 4.4
White Cell Count	970 cells/µL*	< 5
Mononuclear cells	50 cells/µL*	< 3
Polymorphonuclear cells	920 cells/µL*	0
Gram-stain	Gram-positive cocci

a) What is the most likely diagnosis? (10% marks)

b) What is the most appropriate anti-microbial therapy? (15% marks)

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College answer

1. Streptococcal Pneumoniae (pneumococcal) meningitis
2. IV Benzyl Penicillin 2.4g 4-hrly or IV Ceftriaxone 2g 12-hrly Or
IV Moxifloxacin 400mg daily or IV Vancomycin (penicillin or beta-lactam allergy), to target plasma trough levels of 15-20 mg/L

Discussion

Let's go through these data systematically.

The opening pressure, though within the normal range, is still pretty high.
The protein is ridiculously elevated. This could be due to:
- Exudate:
  - Viral or bacterial meningitis, with inflamed meninges exuding the protein
  - Viral or bacterial encephalitis
  - Malignancy, leaking protein into the CSF through immature capillaries and disrupted blood-brain barriers
  - Mycobacterial infection, CNS tuberculosis
  - Seizures
- Local synthesis (eg. of immunoglobulin)
  - Multiple sclerosis
  - Neurosyphilis
  - Sarcoidosis
  - Viral or bacterial meningitis or encephalitis
  - CNS lymphoma
- Decreased resorption:
  - communicating hydrocephalus, eg. due to CNS lymphoma
The glucose is very low. This could be due to:
- Bacterial meningitis
- viral meningitis, to a far lesser extent
- CNS lymphoma
- CNS sarcoidosis
- Subarachnoid haemorrhage (the RBCs also consume glucose)
The cellularity is abnormal (what you might call a pleocytosis). It is neutrophil-dominant, and though we do not have a peripheral blood count, we can assume it is infectious because the neutrophil count is elevanted in the absence of any red cells (theyare not even mentioned).
Gram-positive cocci are swarming throught his sample. That basically solves the riddle for you.

So, the question "what is the most appropriate antimicrobial therapy" really means "which coccus is it?" A betting man would put their money on S.pneumoniae, as that's the most common organism in the community which answers this description. The CLL patient is often found to be immunocompromised due to a failure of humoural immunity, even without cytotoxic treatment, which would put them at risk from these encapsulated organisms (Morra et al, 1999). For the record, the other two organisms commonly seen in this immunoglobulin-deficient population are L.monocytogenes and H.influenzae.

Thus, the most appropriate choice for a suspected S.pneumoniae meningitis (via eTG) is

Benzylpenicillin, if sensitive, or
Ceftriaxone, or
Vancomycin, or if none of these are appropriate,
Moxifloxacin

References

Morra, E., A. Nosari, and M. Montillo. "Infectious complications in chronic lymphocytic leukaemia." Hematology and cell therapy 41.4 (1999): 145-151.

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