Resident Version
Central Nervous System Infections Module
Created by Dr. Wendy Gerstein
Updated 5/09
Objectives:
1) Recognize three clinical symptoms and signs of central nervous system infections.
2) Know three risk factors for particular causes of central nervous system
infections.
3) Be able to adequately choose empiric treatment for bacterial CNS infection, and
order appropriate tests.
References:
1) van de Beek D, de Gans J, Tunkel AR, Wijdicks EFM. Community-Acquired
Bacterial Meningitis in Adults. N Engl J Med 2006; 354: 44-53.
2) de Gans J, van de Beek D. Dexamethasone in Adults with Bacterial Meningitis. N
Engl J Med 2002; 347:1549-56.
3) van de Beek D, de Gans J, Spanjaard L, et al. Clinical Features and Prognostic
Factors in Adults with Bacterial Meningitis. N Engl J Med 2004 351: 1849-59.
HPI: 40 yo male with history of HIV/AIDs, not on HAART, last cd4 count 138, presents
with 3 day history of headache, photophobia, fevers/chills, nausea/vomiting, and “feeling
bad.” Denies visual changes or new skin rashes. Exposure history significant only for
recent trip to Arizona and southern California. Denies any TB exposure or insect bites.
Past Medical History:
HIV/AIDs x 10 years
Herpes zoster
Thrush
Peripheral neuropathy
Hepatitis C
Bipolar disorder
Medications:
Bactrim
Valium
Lithium
Oxycodone/Tylenol
Completed recent course of famvir for herpes zoster lesions on thigh.
Social history: drinks, smokes, uses drugs occasionally (not IV), has sex with men, is a
student.
Family history: negative
PE: T = 98.6, p=77, bp =120/65, rr =12, 95% RA
Gen: alert, oriented, minimal discomfort.
Heent: normal except for few white plagues on buccal mucosa and posterior oropharynx
Neck: no meningismus, supple
Lungs: CTAB
CV: reg, normal exam
Abd: normal
Ext: normal strength, reflexes
Neurological exam – normal, no evidence for any localizing findings.
Skin: crusted lesions on left thigh consistent with healing zoster, no surrounding
redness/swelling, no new lesions present.
Labs: cbc normal except baseline wbc 3.8
Chem 7 and lfts wnl
Head CT without contrast negative
LP results:
Opening pressure 220 mmH20, WBC 88 with 94% lymphocytes, no RBC, protein 97,
glucose 34 (85 in serum).
Gram stain negative.
What is in your differential diagnosis at this point?
With predominant lymphocytes and wbc 88, viral or fungal are more likely. Unable to
rule out bacterial completely with such low cd4 count, so pneumococcus and listeria
cannot be eliminated completely.
Possible viral etiologies: enterovirus, varicella (had h/o recent zoster), WNV, HSV (less
likely with no rbc in LP and no behavioral changes, no h/o oral or genital herpes).
Fungal: coccidioides (recent travel to endemic areas), cryptococcus (common in AIDs
patients). With low cd4 ct other etiologies to worry about include syphilis, TB,
toxoplasmosis, CNS lymphoma. Lastly, drug induced meningitis from bactrim or
ibuprofen use.
What is the next step in management?
Start empiric antibiotics – ampicillin, vancomycin and ceftriaxone.
MRI brain to r/o solitary lesions or changes consistent with HSV due to low CD4 count.
Lab tests: blood, urine and CSF cultures, cryptococcal serum and csf antigen,
coccidioides serum antibody, serum toxo IgG/IgM, Enteroviral PCR, serum RPR and
CSF VDRL, HSV PCR and WNV PCR on CSF, place PPD.
All of the above tests were negative at 48 hours (except PCR studies still pending), MRI
brain completely normal, patient improved.
Now what?
With aerobic and anaerobic cultures negative at 48 hours (cultures and lumbar puncture
done off antibiotics), and CSF findings, it is safe to stop empiric antibiotics. There is no
evidence for HSV with normal MRI and no RBC in CSF. Cryptococcal antigen is very
sensitive, as is coccidioides antibody, and patient is improving with no treatment. Patient
was given a diagnosis of viral/aseptic meningitis of unknown etiology, and on f/u visit all
PCR tests were negative, and patient was back to baseline health.
Outline for discussion:
1) Presentation:
A) Acute bacterial meningitis: fever, stiff neck, headache, mental status changes,
CN palsies, seizures.
B) Viral meningitis: can be more indolent, with prodrome or URI symptoms.
C) Encephalitis: can have more behavioral changes, decreased level of
consciousness.
D) Fungal: can be a more indolent, chronic presentation unless immunsuppressed
(they may present more acutely).
2) Differential: based on exposure history and risk factors. Important to ask about travel
history, insect and animal exposures, underlying immunosuppression.
A) Immunocompetent adults (18-50 years of age): S. pneumoniae, N.
meningitides, enteroviruses, WNV
B) Age >50: S. pneumoniae, L. monocytogenes, Group B strep, GN bacilli, HSV
C) Immunosuppressed/pregnant: L. monocytogenes, Group B strep, GN bacilli,
TB
D) HIV/AIDS: above organisms plus Cryptococcus, Coccidioides immitis, T.
gondii, neurosyphilis
D) Hardware present or history of trauma: S. aureus, GN bacilli, S. epidermidis
E) Not infectious: malignancies, autoimmune diseases, medications
3) Diagnosis:
A) Head CT scan: if patient has a focal neurological exam, altered mental status,
history of seizure activity, or is immunosuppressed. Scan is looking for spaceoccupying lesions, or evidence of increased intracranial pressure (mass effect).
B) Empiric antibiotics before studies if suspecting acute bacterial meningitis.
C) Basic labs, blood cultures, and CSF analysis with lumbar puncture.
Normal csf – 20ml/hr produced, average person with 125-150 ml.
Normal pressure 150 mm H2O, >250 considered elevated.
Normal wbc <5 (<3 pmn’s), normal rbc <5
Normal protein 50% serum, glucose 2/3rd serum.
On any sample, the minimum information obtained should be:
Opening pressure, gram stain, cell count, protein, glucose, anaerobic and
aerobic cultures.
Further studies can be ordered based depend on differential diagnosis/risk
factors.
D) Special studies on CSF: HSV PCR, Enteroviral PCR, WNV PCR, VDRL,
MTB-PCR, AFB stains and culture, fungal stains and culture, Cryptococcal
antigen, Coccidioides antibody.
4) Treatment (goal is antibiotics within one hour of presentation):
A) No gram stain available or negative gram stain:
ampicillin/vancomycin/ceftriaxone (add ampicillin if risk factors present such as
pregnant, immunosuppressed, older age).
B) Gram stain positive:
- GPC: vancomycin/ceftriaxone
- GNC: pen G (chloramphenicol if b-lactam allergic)
- GPR: ampicillin and gentamicin (or bactrim if b-lactam allergic)
- GNR: ceftriaxone and gentamicin
C) Steroids: NEJM 2002 – dexamethasone 10 mg given 15-20 minutes before first
dose of antibiotics reduced relative risk of unfavorable outcome to .50
(significant) in patients with pneumococcal meningitis. It is now standard of care
to administer in adults suspected of having acute bacterial meningitis – the
steroids can be stopped if CSF results not consistent with acute bacterial
meningitis.
D) Viral entities: HSV: acyclovir 10 mg/kg iv q 8 hours. Enteroviral: if PCR
positive, no therapy needed.
E) TB: start 4 drug regimen (ETM, INH, PZA, Rif), steroids
F) Fungal: fluconazole at high doses (800 mg) for coccidioides meningitis. May
also need serial lumbar punctures to lower CSF pressures. Of note, in patients
with fungal meningitis, the fluconazole concentration in cerebrospinal fluid is
approximately 80% of the plasma concentration.
Need to use amphotericin if suspecting or diagnosed cryptococcus or
histoplasmosis meningitis, or for initial therapy of coccidioides in
immunosuppressed patients.
5) Duration:
A) Bacterial: 7-21 days depending on specific organism.
B) Empiric antibiotics with negative CSF at 48 hours (assuming not on antibiotics
as outpatient): discontinue at 48 hours, or sooner if alternative diagnosis obvious.
C) HSV: 21 days iv acyclovir.
D) Fungal: coccidioides – needs treatment indefinitely, cryptococcal – 2 years
with close monitoring.
E) TB: 12 months, steroids for initial 4 weeks.
6) Complications:
A) Overall mortality in community acquired adult bacterial meningitis was 21%
based on prospective evaluation of 696 episodes in the Netherlands.
Pneumococcus was associated with the highest mortality rates and poorest
outcomes.
B) Other risk factors for poor outcome (defined at discharge as focal neurological
deficit, seizures, disability based on Glasgow outcome scale):
Advanced age
Presence of otitis or sinusitis
Absence of rash
Low score on GCS on admission
Tachycardia
Positive blood culture
Elevated ESR
Thrombocytopenia
Low wbc in CSF
Review Questions:
1) 55 yo male with pmhx of controlled diabetes, hypertension, BPH and type I penicillin
allergy, presents with acute onset of headache, fevers, and stiff neck. Physical exam is
notable for patient laying in dark room moaning, temperature 39 C, photophobia,
meningismus but no papilledema. Rest of exam including neurological exam is non-focal.
Labs notable for wbc 18k with left shift, normal kidney and liver function. The ER calls
you to see patient and asks you to do the LP.
Before obtaining the LP, you will:
A) Order head CT to evaluate for abscess; start ceftriaxone, vancomycin and ampicillin;
give .15mg/kg iv dexamethasone, then do LP.
B) Give .15 mg/kg iv dexamethasone, start vancomycin and bactrim, then do LP.
C) Have neurology see the patient first, order head CT, do LP, then start vancomycin and
meropenem.
D) Obtain MRI, give .15mg/kg iv dexamethasone, start vancomycin and ceftriaxone.
2) 34 yo woman presents to the ER with continued headache and fevers. She completed a
14 day course of amoxicillin for presumed acute sinusitis approximately 4 days ago, with
little relief in the drainage or headache, even with ibuprofen and tylenol. Fever and
headache progressed 2 days ago. She denies any visual changes or weakness in her
extremities, and exam is notable for temperature 38.5 C, normal bp and pulse,
photophobia, purulent nasal drainage, negative meningismus, normal neurological exam.
The ER doctor performs an LP which shows the following:
Normal opening pressure, WBC 10 with 70 % lymphs, 25% neutrophils. RBC 0, glucose
60 (serum 95), protein 60, gram stain negative. You are asked to admit the patient.
Your next step in management is:
A) Reassure the patient and ER doctor that this is a normal finding after recent therapy
for sinusitis, prescribe a 2 week course of oral levofloxacin for resistant sinusitis, and
arrange follow up appointment in one week time.
B) Admit patient, start vancomycin and ceftriaxone, and if cultures negative at 48 hours,
stop therapy with a diagnosis of aseptic meningitis (most likely from ibuprofen).
C) Admit patient, start vancomycin and ceftriaxone, order non-contrasted head CT scan
for the following morning.
D) Admit patient, start vancomycin and ceftriaxone, call the radiology resident to obtain
urgent contrasted head CT scan.
Post Module Evaluation
Please place completed evaluation in an interdepartmental mail envelope and address to
Dr. Wendy Gerstein, Department of Medicine, VAMC (111).
1) Topic of module:__________________________
2) On a scale of 1-5, how effective was this module for learning this topic? _________
(1= not effective at all, 5 = extremely effective)
3) Were there any obvious errors, confusing data, or omissions? Please list/comment
below:
________________________________________________________________________
________________________________________________________________________
________________________________________________________________________
________________________________________________________________________
4) Was the attending involved in the teaching of this module? Yes/no (please circle).
5) Please provide any further comments/feedback about this module, or the inpatient
curriculum in general:
6) Please circle one:
Attending
Resident (R2/R3)
Intern
Medical student