Central nervous system infections
3 quick cases….
Case 1
67 yo woman Past history
– Type 2 DM– HT
Presented to ED via ambulance– called by daughter (who lives in Frankston)
Difficult historian– On questioning says has had headaches for 2
days– Lethargy, anorexia
Case 1
On examination– Drowsy but eye opens to voice– Disoriented to time but not place– Febrile T 37.8– Chest clear– FWT leucocyte, nitrite positive
Case 1
Differential diagnosis?
Case 1
Daughter noticed patient to be ‘vague’ and saying strange things over the phone last 4 days
Didn’t mention to daughter about headache
Telephoned her at 3.30 am that morning asking her where her cat was
Case 1
FBE: wbc 12, PMN 9CRP 123Electrolytes normalMSU: wcc 32
Next…..
Case 1
CT brain normalLP:
– wcc 15, 100% lymphocytes– rcc 3– Protein 0.35 g/l– Glucose normal
Case 1
Diagnosis?
Case 1
After d/w ID started on iv aciclovir and benzylpenicillin
2 days later HSV PCR on CSF positiveMRI brain:
HSV encephalitis
Case 2
27 yo female Brought in to ED 10pm Saturday night by
boyfriend Complaining of severe headache, present 2
days. Supposed to go to Sydney for the weekend but cancelled Friday because ‘felt like crap’. Assoc nausea, lethargy.
Feeling hot and flushed
Case 2
Examination– Lying curled up in dark cubicle– Not opening her eyes when talking to you
but able to answer all questions– Got up to go to toilet just after seen– T 36.8– Pulse 88, BP 115/80– Warm, well perfused
Case 2
Differential diagnosis?What next?
Case 2
CT brain normalFebrile T 38.4 when returns from CTLP:
– wcc 32070% PMN, 30% lymphocytes
– rcc 4– Protein 0.48 g/l– Glucose 3.2
Case 2
Diagnosis?
Case 2
No antibiotics givenAdmitted for analgesia, hydrationRecovered quickly, home Monday
morningEnterovirus PCR negative
Case 3
16yo boyPresents with 5 day history of
headaches, fevers‘Bad’ headaches. Some relief with
paracetamol but getting worse so presented to ED
URTI week prior but this resolved mostly
Case 3
On examination alert and oriented, no neck stiffness. No neuro signs. Febrile T38.1
FBE: wbc 11, PMN 8LFT, U+E normalCRP 300
Case 3
Differential diagnosis?What next?
Case 3
Sent home with analgesia, GP letter36 hrs later bld cultures flagged
positive for GPCWhat to do?
Case 3
Patients parents called. Instructed to present to GP
GP referred back to EDOn arrival still headache, orientedCRP 330Referred to medical team ?LPCT brain performed, reported as
normal
Case 3
LP– wcc 8
100% PMN– rcc 1– Prot 0.38– Gluc normal
Case 3
Significance of this result?
Case 3
AdmittedCT changed to report sphenoid
sinusitisAntibiotics with-held ? Viral24 hours after admission:
– decreased conscious state– ARDS– ICU
Bld cultures: Strep milleri
Case 3
Despite broad-spectrum antibiotics and ENT surgery pt deteriorated
CNS infections
Headache– Meningitis– Para-meningeal infection
Confusion/seizure/focal signs– Encephalitis– Brain abscess
**History of symptoms at beginning of illness and duration crucial in differential diagnosis
Meningitis
Acute meningitis– Bacterial– Viral
‘Chronic’ meningitis– Tuberculosis– Fungal (Cryptococcal)– Non-infectious (malignant, sarcoid)
Acute bacterial meningitis
Bacterial meningitis clinical presentation HEADACHE
– Severe– Can be sudden onset– Rapidly worsens
Fever– Sometimes afebrile/hypothermia– History of fever (v’s making diagnosis based on
temperature on arrival in ED) Neck stiffness common but not sensitive
enough to exclude dgx
Bacterial meningitis clinical presentationOnset of illness
– Patients often feel very unwell early and present within hours of onsetAverage time to presentation <24hrs
Severe myalgias indicate bacterial sepsis
More unwell than patients with viral meningitis: drowsy, pale, hypotension, tachycardia.
Bacterial meningitis - diagnosis
CSF Bacterial meningitis
Viral meningitis
Cell count(<4 LØ/mL)
>1000 <500
Differential >90% PMN LØ predom (may be PMN early)
Protein (0.2-0.4g/L)
>1 0.4-1
Glucose (2/3 of serum)
Decreased Normal
Aetiology
Neisseria meningitidis– Children and young adults
Streptococcus pneumoniae– All ages
Listeria monocytogenes– Infants and elderly
Haemophilus influenzae type B
N.meningitidis
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1999 2001 2003 2005 2007
meningoccocalnotifications australia
N.meningitidis
S.pneumoniae – CSF and blood culture isolate penicillin sens
Beta-lactam resistant S.pneumoniae Penicillin MIC:
SENS RES≤0.06 ≥0.12 mcg/mL
Penicillin levels approx 0.5 in CSF
Ceftriaxone MIC:SENS INT RES ≤0.5 1 ≥2 mcg/mL
Ceftriaxone levels approx 0.5-4 in CSF
Listeria meningitis
2nd most common cause of bacterial meningitis in adults >50
Even more common if immunosuppressed
Can produce meningoENCEPHALITISCan be culture negativeResistant to cephalosporins, sensitive
to penicillin
Listeria meningoencepalitis
Management of possible bacterial meningitisFocus is ensuring rapid administration
of treatment whilst attempting diagnosis– Lumbar puncture– Antibiotics– Corticosteroids– CT brain
Management of possible bacterial meningitisDelay in antibiotics leads to greater
mortality and worse neurological outcome– Delay >3hrs from time of arrival: mortality
OR 14 (Auburtin et al, Crit Care Med. 2006)
Management of possible bacterial meningitisFactors associated with delay in
antibiotics– Afebrile at presentation– Triage to physician time– Time from LP to abx– CT brain!!
Sequence of CT then LP then abx
Management of possible bacterial meningitisIs a CT brain required before LP in
adults with suspected meningitis?– 5% of patients will have mass effect– All of those with significant mass effect:
ImmunosuppressedAge >60Focal neuro/seizures/decreased
consciousness/papilloedema– In the absence of these features safe to
perform LP without CT brain(Hasbun NEJM 2001)
Management of possible bacterial meningitisSequence of management either:
1. LP then abxOR2. Abx then CT then LP
NOT CT then LP then abx
Management of possible bacterial meningitisCorticosteroids?
– Dexamethasone 10mg 6hrly 4 days– Started just prior to abx– Possibly not effective if started later– Reduction in mortality from 34% to 14%
Mostly from S.pneumoniae group(de Gans et al NEJM 2002)
Management of possible bacterial meningitisEmpiric antibiotics
– Ceftriaxone 2g 12 hourly (S.pneumo, N.meningitidis)
– Benzylpenicillin 2.4g 4 hourly (listeria)– Vancomycin (high dose, aim levels 20-
30) (ceftriaxone/pen resistant S.pneumo)
– Other Moxifloxacin? Rifampicin?
Viral meningitis
Viral meningitis
EnterovirusesNot as unwell (no hypotension, no
decreased conscious state)Self limitedBut it does hurt!CSF Enterovirus PCR
Viral meningitis
CSF Bacterial meningitis
Viral meningitis
Cell count(<4 LØ/mL)
>1000 <500
Differential >90% PMN LØ predom (may be PMN early)
Protein (0.2-0.4g/L)
>1 0.4-1
Glucose (2/3 of serum)
Decreased Normal
Viral meningitis
There is a differential diagnosis of ‘sterile’ meningitis with acute presentation– Tb, cryptococcal– Parameningeal infections– HIV, mumps, rat-lungworm
Measure pressure and get plenty of CSF (most people can tolerate 10-20ml). Lots of tests to do!
Cranial parameningeal infections
Cranial parameningeal infectionsResult from sinusitis
– Mastoid, frontal most common– Sphenoid and ethmoid more difficult to
diagnoseOsteomyelitis -> epidural -> subdural -
> brain abscessSuspect when history of sinus
symptoms then worsening headache
Cranial parameningeal infectionsDiagnose with imaging
– Need MRI for ethmoid/sphenoid sinusesCSF variable. Increased wcc 15- to
>1000 Management:
– Broad spectrum abx covering S.aureus, Strep, anaerobes
– Urgent surgical referral
Encephalitis
Encephalitis
Focal neurological signs, seizure, confusion, decreased conscious state
Can be some headache but this isn’t the primary symptom
+/- fever
Encephalitis
HSV-1Wide-spectrum of other viruses and
microorganisms– MVE, West-Nile, Nipah
ListeriaMany go undiagnosed
CSF with encephalitis
CSF Encephalitis Bacterial meningitis
Viral meningitis
Cell count(<4 LØ/mL)
<100 >1000 <500
Differential LØ predom >90% PMN LØ predom (may be PMN early)
Protein (0.2-0.4g/L)
Normal to slight incr
>1 Normal to slight incr (<1)
Glucose (2/3 of serum)
Normal Decreased Normal
HSV Encephalitis
HSV PCR very sensitive and specific. Can be negative early in course of disease
HSV encephalitis
iv aciclovirPrognosis depends on degree of
impairment at presentation
Brain abscess
Focal signs, fever and headache Presentation often more prolonged
– Days to weeks– But can present with eg seizure in previously well
person Source
– Contiguous– Haematogenous: lung abscess, dental
Strep milleri group, S.aureus
Management: surgery and prolonged abx
Central nervous system infections Precise history essential to diagnosis CSF findings very helpful in confirming
diagnosis Medical (or surgical) emergency
– Prioritise patients and act quickly– When suspect bacterial meningitis don’t let
imaging delay therapy Don’t forget steroids and vanc for bacterial
meningitis Call ID team!!
Ms IN
Cellulitis RCT at TNH
Trial of iv abx versus oral abx for cellulitis at The Northern.
Refer any patient in whom you would consider iv abx (even 1 dose or even if you aren’t sure)– Can be planned for inpatient stay or ready for
discharge– Don’t try to look for inclusion or exclusion
criteria yourself.– If patient accepted then we take over
management