This document discusses a case of acute meningitis in a 19-year-old student who presented with fever and headache. On the third day, he developed severe headache, vomiting and was disoriented. His CSF analysis showed turbid, milky white fluid with elevated white blood cells and proteins. Gram stain of CSF showed chains of gram-positive cocci and cultures grew Streptococcus pneumoniae. The document then discusses symptoms, signs, clinical presentation and diagnostic evaluation of acute bacterial meningitis as well as appropriate antibiotic treatment and duration. It addresses questions around partially treated meningitis versus tuberculous meningitis, the role of repeated LP, risk factors for poor outcome and nosocomial meningitis.

1. Symposium on “Issues In Neurology”
Pyogenic meningitis

2. Case vignette
• A 19 yrs old student presented with
fever, and headache of 2 days duration
• He was treated with antipyretics.
• On day 3, he had severe headache,
vomiting and was disoriented.

3. Symptoms of meningitis
• Traditional “Triad of symptoms”
– Fever, neck stiffness, and altered mental
status.

5. Symptoms & signs of Meningitis
• Prospective study (n=696)
• community-acquired acute bacterial meningitis,
confirmed by CSF cultures
• The classic triad in only 44 percent of episodes

6. • 44% had the Triad
• 95% had 2 out of 4
• 4% had only one
• 1% had none
Neck stiffness
(83%)
Fever(71%)
Change in
mental
status(69%) Head ache(87%)

7. Symptoms & signs of Meningitis
Uncommon:
• Seizures in 15-40% (common in pneumococcal
meningitis).
• Focal neurological deficits
• Papilloedema.

8. Clinical clues to etiological diagnosis:
• Recurrent seizure –Pneumococcal .
• Rashes – Menigiococcemia,
Rickettesia
• CSF leak – S. Pneumonia.

9. • Premeningitis phase?
• Any symptom to say onset of bacterial
seeding of meninges?

10. Pre meningitis phase?
• Review of 27 studies (n= 5585)
• Could not identify any specific “symptom”
denoting a “premeningitis” phase or
heralded the onset of bacterial seeding of
the CNS*
*Bonadio WA. Medical-legal considerations related to symptom duration and patient outcome
after bacterial meningitis. Am J Emerg Med 1997; 15:420–3.

11. Case vignette
• On examination he was confused and
irritable. His optic disc was normal, had
positive Kernig’s sign; had no focal
neurological deficits and plantars were
flexor.
• How often do the clinical signs of meningitis
present in bacterial meningitis?

12. How often do the clinical signs of meningitis
present in bacterial meningitis?
• Meningeal signs may be absent in
– extremes of age,
– immunocompromised individuals,
– severely depressed mental status.
• False positive in cervical spine disease in older
individuals

13. • 297 adults with suspected meningitis were
prospectively evaluated for the presence of
these meningeal signs before lumbar
puncture was done.

15. How often do the clinical signs of meningitis
present in bacterial meningitis?
• Classical meningeal signs : sensitivity-
5% to 30%
• Absence of clinical meningeal signs does
not rule out the diagnosis of bacterial
meningitis.

16. New sign: “Jolt accentuation”
• Exacerbation of an existing headache with rapid
head rotation.
• A small prospective study of 54 patients with
meningitis found that jolt accentuation had a
sensitivity of 97% (Uchihara T et al, 1991).
• not been evaluated in any subsequent studies .

17. Case vignette
• Clinically he was diagnosed as acute
meningitis-Community acquired.
• What should be the next step in the
order of preference?

18. Suspected acute
Meningitis
Blood culture
Dexamethasone &
emperical antibiotics
CT SCAN
LP CSF analysis
CSF suggestive of
bacterial meningitis

19. Gram stain
Culture
Positive
Dexa+Targetted
antibiotics
Negative Dexa+Emperical
antibiotics

20. Which Patients with Suspected Meningitis
Should
Undergo CT prior to LP?

21. Recommended criteria for adult patients with
suspected bacterial meningitis who should undergo CT
prior to lumbar puncture (B-II).
Criterion Comment
Immunocompromised state HIV infection or AIDS, receiving immunosuppressive
therapy, or after transplantation
History of CNS disease Mass lesion, stroke, or focal infection
New onset seizure Within 1 week of presentation; some authorities would
not perform a lumbar puncture
on patients with prolonged seizures or would delay
lumbar puncture for 30
min in patients with short, convulsive seizures
Papilledema Presence of venous pulsations suggests absence of
increased intracranial pressure
Abnormal level of
consciousness …
Focal neurologic deficit Including dilated nonreactive
pupil, abnormalities of ocular motility, abnormal visual
fields, gaze palsy, arm or leg drift

22. Case vignette
• Blood culture taken, started on dexamethasone
with empirical antibiotics (Ceftriozone &
Vancomycin)
• Patient’s CT scan of brain was normal. He
underwent Lumbar Puncture and CSF analysis.

23. Case vignette
• CSF was turbid, milky white in colour.
– 1400 cells/ cumm, 90% polymorphs,
– sugar 10mgs%, protein 200mgs%,
• What is the role of Gram stain? What is the role
of Sr C-Reactive Protein and Sr Procalcitonin
estimation? What are the newer tests
available?

24. In untreated bacterial meningitis,LP CSF:
• WBC count 1000– 5000 cells/mm3,
• ( <100 to 110,000 cells/mm3).
• 80% to 95% Neutrophils;
– ∼10% lymphocyte predominance
• CSF glucose <40 mg% in 50%–60% of patients;
• CSF protein is elevated in virtually all patients
• CSF cultures positive in 70%–85% of patients
who have not received prior antimicrobial
therapy

25. What Laboratory Testing May Be Helpful in
Distinguishing
Bacterial from Viral Meningitis?
422 pts with acute bacterial or viral meningitis*
• CSF glucose <34 mg%, a ratio of CSF to blood
glucose of <0.23,
• CSF protein concentration of >220 mg%
• CSF leukocyte count of >2000 leukocytes/mm3,
• CSF neutrophil count of >1180 neutrophils/mm3
*Spanos A, Harrell FE Jr, Durack DT. Differential diagnosis of acute meningitis: an
analysis of the predictive value of initial observations.JAMA 1989; 262:2700–7.

26. CRP
• Sensitivity: 69% to 99%
• Specificity: 28% to 99%
• Normal CRP has a high negative
predictive value in the diagnosis of
bacterial meningitis (B-II).

27. Procalcitonin
• Sensitivity94%,
• Specificity was 100%.
•
Gendrel D, Raymond J, Assicot M, et al. Measurement of procalcitonin levels in children
with bacterial or viral meningitis. Clin Infect Dis 1997; 24:1240–2.

28. CSF lactate
• CSF lactate concentrations of 14.2 mmol/L*
– Sensitivity 96%,
– Specificity 100%,
– positive predictive value was 100%,
– negative predictive value was 97%
• In the postoperative neurosurgical patient,
initiation of empirical antimicrobial therapy
should be considered if CSF lactate
concentrations are 4.0 mmol/L, pending
results of additional studies (B-II).
*Genton B, Berger JP. Cerebrospinal fluid lactate in 78 cases of adult
meningitis. Intensive Care Med 1990; 16:196–200.

29. Gram stain
• 92% sensitive and 99% specific
– in patients who had not received antimicrobial
therapy before LP(Dunbar SA et al., 1998).
• The sensitivity of CSF Gram stain is
significantly reduced
– when the bacterial pathogen is a gram-
negative bacilli or L monocytogenes,
– when a LP is performed after the initiation of
antibiotics (Tunkel AR et al., 2004).

30. Latex agglutination tests.
• They are simple to perform, organism specific, and
yield results in less than 15 minutes.
• The sensitivity of these tests is fairly good:
– 78% to 100% for H. influenzae type B,
– 67% to 100% for S. Pneumoniae,
– 50% to 93% for N. Meningitides (Tunkel AR et al.,
2004).
• Latex agglutination may be most useful for the
patient who has been pretreated with antimicrobial
therapy and whose Gram stain and CSF culture
results are negative (B-III).

31. PCR
• Sensitivity and Specificity of PCR were
both 91%.
– CSF samples of 54 pts with and without
meningococcal disease*
*Ni H, Knight AI, Cartwright K, et al. Polymerase chain reaction for
diagnosis of meningococcal meningitis. Lancet 1992; 340:1432–4.

32. Syndrome
Signature
Specific
amplification
The amplified product is
introduced onto a
Syndrome signature
Evaluation Protocol
Then it undergoes a process called
Signature specific Hybridization, Then an enzymatic
reaction occurs and a
colored spot appears..

33. MENINGITIS

34. SES AES Lab Validation – NIMHANS , n=418
Group Category Conventional
Assay
SES Result
I Proven AES 131/ 131 128^ / 131 (97%)
II Suspected AES 0 /127 80 / 127 (64%)
III Infections not AES 0 / 78 8 / 78*
IV NIND 0 / 90 12** / 90
V Healthy Controls 0/ 50 0 / 50
** Tumour pts on chemotherapy; * HIV Positive TB/ Crypto / Toxo
On press, Courtesy Prof B Ravikumar & Prof Sankar NIMHANS,
Bangalore

35. Case vignette
• His Sr.CRP was high. CSF : Gram stain
showed chains of Gram +ve cocci.
Blood and CSF Culture: S. Pneumoniae
grown.
• What is the antibiotics of choice and
How long to be given?

36. Case vignette
1. Inj. Ceftrioxone 2g IV Q12th hourly
2. Inj. Vancomycin 500mg in 100ml of NS IV
Q 8th hourly
– continued for 14 days.
–
• Before first dose of antibiotics one dose of
Inj. Decadron 8mg IV and then 8th hourly
for initial 4 days.

37. How Quickly Should Antimicrobial Therapy Be
Administered
to Patients with Suspected Bacterial Meningitis?
• 305 pts of bacterial meningitis *
– 53 patients (17.4%) received an antimicrobial agent
prior to admission; there was only 1 death (1.9%),
– 252 pts did not receive antibiotics prior to admission;
there were 30 deaths (12%)
*The Research Committee of the British Society for the Study of Infection.Bacterial
meningitis: causes for concern. J Infect 1995; 30:89–94.

38. Recommendations for empirical antimicrobial therapy
for purulent meningitis based on patient age and
specific predisposing condition (A-III).
Predisposing factor Common bacterial pathogens Antimicrobial therapy
2–50 years N . meningitidis, S.
pneumoniae
Vancomycin plus a third-
generation cephalosporin
>50 years S. pneumoniae, N.
meningitidis, L.
monocytogenes,
aerobic gram-negative bacilli
Vancomycin plus ampicillin
plus a third-generation
cephalosporin

39. Once the Bacterial Etiology of Meningitis Is
Established, What Specific Antimicrobial
Agents Should Be Used for Treatment?

40. Recommendations for specific antimicrobial therapy in
bacterial meningitis based on isolated pathogen and
susceptibility testing.
Microorganism,
susceptibility
Standard therapy Alternative therapies
Penicillin MIC
<0.1 mg/mL
0.1–1.0 mg/mLb
>2.0 mg/mL
Cefotaxime or ceftriaxone
MIC
>1.0 mg/mL
Penicillin G or ampicillin
Third-generation
cephalosporine
Vancomycin plus a third-
generation cephalosporins
Vancomycin plus a third-
generation
cephalosporina,
Third-generation
cephalosporin,a
chloramphenicol
Cefepime (B-II),
meropenem (B-II)
Fluoroquinoloned (B-II)
Fluoroquinoloned (B-II)
Neisseria meningitidis

41. Microorganism,
susceptibility
Standard therapy Alternative therapies
Neisseria meningitidis
Penicillin MIC
<0.1 mg/mL
0.1–1.0 mg/mL
Penicillin G or ampicillin
Third-generation
cephalosporins
Third-generation
cephalosporin,
chloramphenicol
Chloramphenicol,
fluoroquinolone, meropenem
Listeria monocytogenes Ampicillin or penicillin G Trimethoprim-
sulfamethoxazole, meropenem
(B-III)
Escherichia coli and
other Enterobacteriaceaeg
Third-generation
cephalosporin (A-II)
Aztreonam, fluoroquinolone,
meropenem,
trimethoprimsulfamethoxazole,
ampicillin
Pseudomonas aeruginosa Cefepimee or
ceftazidimee (A-II)
Aztreonam,e ciprofloxacin,e
meropeneme

42. Microorganism,
susceptibility
Standard therapy Alternative therapies
Haemophilus influenzae
b-Lactamase negative
b-Lactamase positive
Ampicillin Third-generation
cephalosporin,a cefepime,
Third-generation
cephalosporin (A-I)
Cefepime (A-I),
chloramphenicol,
fluoroquinolone
chloramphenicol,
fluoroquinolone
chloramphenicol,
fluoroquinolone
Staphylococcus aureus
Methicillin susceptible
Methicillin resistant
Nafcillin or oxacillin
Vancomycinf
Vancomycin, meropenem
(B-III)
Trimethoprim-
sulfamethoxazole, linezolid
(B-III)
Staphylococcus epidermidis Vancomycin Linezolid (B-III)
Enterococcus species
Ampicillin susceptible
Ampicillin resistant
Ampicillin and vancomycin
resistant
Ampicillin plus gentamicin
Vancomycin plus
gentamicin …
Linezolid (B-III)

43. What Are the Indications for Repeated LP
in Bacterial Meningitis?
• Any patient who has not responded clinically
after 48 h of appropriate antimicrobial therapy
(A-III).

44. Antibiotics how long?
Microorganisn Duration of therapy in days
Neisseria meningitidis 7
Haemophilus influenzae 7
Streptococcus pneumoniae 10-14
Streptococcus agalactiae 14-21
Aerobic gram-negative bacillia 21
Listeria monocytogenes 21

45. Risk factors for an unfavorable
outcome
• Advanced age,
• Presence of otitis or sinusitis,
• Absence of rash,
• A low score on the GCS
• On admission,
– tachycardia,
– a positive blood culture,
– an elevated ESR,
– thrombocytopenia,
– a low CSF white-cell count.

46. FAQs
• Partially treated pyogenic meningitis Vs
Tuberculous meningitis…

47. FAQs
• Clinically bacterial meningitis
• Started on empirical antibiotic
• LP CSF TURBID
• Cell count just 100 ; sugar < 20mg%
Protein 220mg%
• Pt was responding well
• Repeat LP CSF showed 1000 cell ????

48. FAQs
Basilar skull
fracture
S. pneumoniae, H. influenzae,
group A b-hemolytic
streptococci
Vancomycin plus a third-
generation
cephalosporin

49. FAQs
Penetrating
trauma
Post neurosurgery
CSF shunt
1. Staphylococcus aureus,
2. aerobic gram-negative
bacilli (including
Pseudomonas aeruginosa)
3. coagulase-negative
staphylococci (especially
Staphylococcus
epidermidis),
Vancomycin plus
cefepime,
vancomycin plus
ceftazidime,
or vancomycin plus
meropenem

50. FAQs
• CSF Shunt related Bacterial Meningitis , Is It
Necessary to Administer Antimicrobial Therapy
by the Intraventricular Route?
• Does the Shunt Need to Be Removed for
Optimal Therapy, and When Can a New Shunt
Be Implanted?

51. FAQs
• Nosocomial meningitis
– Gram negative bacilli
• Enterobacteriaceae family;Ecoli,Klebsiella
• Pseudomonas
– Gram positive cocci
• Staph ,pneumococcus
– Multistrain resistant Acinetobacter baumannii

52. FAQs
• Multistrain resistant Acinetobacter
baumannii
– Rod shaped gram negative
– Petechial rash
– Waterhouse friderichsen syndrome
• Carbapenums

53. FAQs
• Role of cabapenums in bacterial
meningitis

54. Swarts et al NEJM 2004

55. Message
• Bacterial meningitis is a life threatening or brain
threatening medical emergency
• High index of suspicion is mandatory
• Clinical signs and symptoms has its own
limitations
• Follow the step “wise” approach
• Differential diagnosis with CSF report : cautious
• If not improving by 48 hrs....

56. Symposium on “Issues In Neurology”
Pyogenic meningitis