Noon conference sheils 011719

1. Noon Conference
Catherine Sheils PGY1
1/17/2019

2. © 2016 Virginia Mason Medical Center 2
Objectives
Bacterial Meningitis
• Clinical presentation
• Mortality and risks
• Workup
• Diagnostic tests
• Interpretation of CSF results
• Treatment
• Antibiotics
• Vaccination

3. © 2016 Virginia Mason Medical Center
Mortality and Risks
3
• Untreated, mortality approaches 100%
• With appropriate treatment, mortality ~25%
• Hypotension, AMS, seizures at
presentation associated with greater
mortality
• Strep pneumo meningitis
• Increased risk of persistent cognitive
dysfunction (21% vs 6%)
• Higher mortality (14% vs 4%)

4. © 2016 Virginia Mason Medical Center
Clinical presentation
“Classic Triad” * Prevalence
Fever
95% at presentation, additional 4% within 24 hr
Nuchal rigidity
88% on initial exam, persists > 7 days in most
patients
Altered mental status
78% on presentation; 22% responsive only to pain;
6% unresponsive to all stimuli
4
*more likely in pneumococcal meningitis than meningococcal
Sensitivity 5-25%
Specificity 87-95%

5. © 2016 Virginia Mason Medical Center
Etiology
5
Organism Risk factors Clinical sx
Mastoiditis, sinusitis,
otitis media
Classic triad
Hearing loss
Children and young
adults
Petechiae and palpable
purpura (64%)
Septic arthritis
Age > 50
Immunocompromised
Infants
Small brain abscesses
Seizures
Focal neurologic deficits (37%)
Ataxia, CN palsies, nystagmus
Incidence decreased
due to vaccine

6. © 2016 Virginia Mason Medical Center
Etiology
6
Organism Risk factors Clinical sx
Strep pneumoniae
(71%)
Mastoiditis, sinusitis,
otitis media
Classic triad
Hearing loss
Children and young
adults
Petechiae and palpable
purpura (64%)
Septic arthritis
Age > 50
Immunocompromised
Infants
Small brain abscesses
Seizures
Focal neurologic deficits (37%)
Ataxia, CN palsies, nystagmus
Incidence decreased
due to vaccine

7. © 2016 Virginia Mason Medical Center
Etiology
7
Organism Risk factors Clinical sx
Strep pneumoniae
(71%)
Mastoiditis, sinusitis,
otitis media
Classic triad
Hearing loss
Neisseria meningitis
(12%)
Children and young
adults
Petechiae and palpable
purpura (64%)
Septic arthritis
Age > 50
Immunocompromised
Infants
Small brain abscesses
Seizures
Focal neurologic deficits (37%)
Ataxia, CN palsies, nystagmus
Incidence decreased
due to vaccine

8. © 2016 Virginia Mason Medical Center
Etiology
8
Organism Risk factors Clinical sx
Strep pneumoniae
(71%)
Mastoiditis, sinusitis,
otitis media
Classic triad
Hearing loss
Neisseria meningitis
(12%)
Children and young
adults
Petechiae and palpable
purpura (64%)
Septic arthritis
Listeria monocytogenes
(4%)
Age > 50
Immunocompromised
Infants
Small brain abscesses
Seizures
Focal neurologic deficits (37%)
Ataxia, CN palsies, nystagmus
Haemophilis Influenza
(6%)
Incidence decreased
due to vaccine
Group B strep
(7%)

9. © 2016 Virginia Mason Medical Center
Empiric Treatment
9
Predisposing
Factor
Organism Regimen
Age 2 - 50 S. pneumoniae, n. meningitidis
Vancomycin
Ceftriaxone/cefotaxime
Age 50+
S. pneumoniae, n.
meningitidis, listeria
Vanco
Ceftriaxone/cefotaxime
plus ampicillin
Basilar skull
fracture
S. pneumoniae, n.
meningitidis, GAS
Vancomycin
Ceftriaxone/cefotaxime
Post NSGY
Gram negative rods (including
pseudomonas), staph aureus,
coag neg staph
Vancomycin
Cefepime OR meropenem
Immunocomprom
ised
S. pneumoniae, n.
meningitidis, listeria, gram
negative rods inc.
pseudomonas
Vancomycin
Plus ampicillin AND cefepime

10. © 2016 Virginia Mason Medical Center
Dexamethasone
• Cochrane 2015 meta-analysis of 4121
individual patients, 25 RCTs
• No difference in mortality in all pts
• Significant difference in pts with strep pnemo
meningitis
• 14% vs 34% mortality
• No increase in GIB
• Lower rates of severe hearing loss and
other neuro sequelae
• Q6 hours, 4 days
• First dose with abx
10

11. © 2016 Virginia Mason Medical Center
Workup
- Blood cultures
- Lumbar puncture
- Head CT?
- Empiric antibiotics
11

12. © 2016 Virginia Mason Medical Center
To CT or not to CT?
IDSA guidelines (2004)
CT head if:
- Immunocompromised
- Hx of CNS disease
- Seizure
- Papilledema
- Altered consciousness
- Focal neurologic deficit
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13. © 2016 Virginia Mason Medical Center 13
Immunocompromise
Hx of CNS disease
Seizure
Papilledema
Altered consciousness
Focal neurologic deficit
NO YES
Blood cultures
LP
Dexamethasone
Empiric antibiotics
Narrow abx based
on gram stain, CSF
studies
Blood cultures
Dexamethasone
Empiric antibiotics
CT head
If negative then LP

14. © 2016 Virginia Mason Medical Center
Delay in treatment
- CT head is ordered too frequently
- 2017 study of IDSA guidelines: 60% non
compliance
- Head CT ordered when not indicated in
355/549 (64%)
- Not done when indicated in 13/207 (0.6%)
- CT scan before LP leads to avg 2 hour
delay in diagnosis, 1 hour delay in
therapy
- Treatment delay leads to 13% increase
in mortality per hour (2018 study)
14

15. © 2016 Virginia Mason Medical Center
CSF studies
15
Bacterial meningitis Our patient
Opening pressure 200-500
Leukocytes 1000-5000
Neutrophil predominance
Glucose < 40
Protein 100-500
Gram stain positive in 60-
90%
Culture positive in 70-85%
? Opening pressure
Leukocytes 13412
79% neutrophils
Glucose 38
Protein 510
Gram stain with GPCs in
chains
Culture pos 4+ strep pneumo

16. © 2016 Virginia Mason Medical Center
Pneumococcal vaccination
- Cochlear implant, CSF leak, or hx of
pneumococcal disease
- Give PCV13 and PPSV23 > 8 weeks
later
- Once 65, give another dose of
PPSV23, and revaccinate every 5-10
years
16

17. © 2016 Virginia Mason Medical Center
Our 43 year old gentleman
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right lung nodules and infiltrates
• ED treatment
• CT scan: no intracranial lesion but bilateral mastoiditis
• LP performed (abx delay?)
• Initially started on vancomycin, ceftriaxone, acyclovir, and
dexamethasone
- Acyclovir dc’d after CSF studies, Vancomycin was discontinued after culture
- Transfer to Providence St Peter ICU
• ENT evaluation: bilateral PE tubes, purulent drainage
• Pesistent left otorrhea concerning for CSF leak
• Transfer to VM CCU
• Bradycardic to HR 30s (?vagal tone 2/2 CNS inflammation)
• Defervesced, ongoing nuchal rigidity, ?affect, hearing loss
• NSGY input: s/p lumbar drain, acetazolamide
• ID input: cont dexamethasone, ceftriaxone. HIV neg.
• Vaccinated with PSV13, 23 valent 8 weeks later.
• Skull base surgery planned neurosurg/ENT

18. © 2016 Virginia Mason Medical Center
Illness Scripts
18
Bacterial Meningitis Viral meningitis
Pathophysiology
Strep pneumo
N. Meningitidis
H. flu
Listeria
GBS
Enterovirus
Herpesvirus 1, 2
VZV
CMV
EBV
HH6
West Nile, St. Louis, Califormia
Epidemiology
Immune competent
Elderly (listeria)
Summer months (mosquito borne)
May and November (enterovirus)
Herpesvirus (year round)
Time course Acute/subacute Acute/subacute
Clinical
presentation
Altered mental status, nuchal rigidity, fever,
neuro sx, rash/arthralgia
Headache, fever, nuchal rigidity, n/v, myalgias,
maculopapular rash
Diagnostics
Opening pressure 200-500
Leukocytes 1000-5000
Neutrophil predominance
Glucose < 40
Protein 100-500
Gram stain positive in 60-90%
Culture positive in 70-85%
Opening pressure < 250
Leukocyte count 50-1000
Lymphocyte predominance
Glucose > 45
Protein < 200
Gram stain negative
Culture negative
Therapeutics
Antibiotics (Vanc, third gen cephalosporin,
ampicillin if risk factors) plus dexamethasone
Acyclovir for HSV/VZV
Supportive for Enterovirus, WNV, St Lous,
California

19. © 2016 Virginia Mason Medical Center
References
- MKSAP 2018 Infectious Disease
- Up to Date pages:
- Dexamethasone to prevent neurological complications of bacterial
meningitis in adults.
- Clinical features and diagnosis of acute bacterial meningitis in adults.
- Treatment of bacterial meningitis caused by specific pathogens in adults.
- Initial therapy and prognosis of bacterial meningitis in adults.
- Brower MC, McIntyre P, Prasad K, van de Beek D. Corticosteroids for acute
bacterial meningitis. Cochrane Database of Systematic Reviews 2015, Issue 9. Art.
No. : CD004405. DOI: 10.1002/14651858.CD004405.pub5.
- Glimaker, M., et al. (2015). "Adult bacterial meningitis: earlier treatment and
improved outcome following guideline revision promoting prompt lumbar puncture."
Clin Infect Dis 60(8): 1162-1169.
- Glimaker, M., et al. (2018). "Lumbar Puncture Performed Promptly or After
Neuroimaging in Acute Bacterial Meningitis in Adults: A Prospective National Cohort
Study Evaluating Different Guidelines." Clin Infect Dis 66(3): 321-328.
- Hasbun (2017). "Cranial Imaging Before Lumbar Puncture in Adults With
Community-Acquired Meningitis: Clinical Utility and Adherence to the Infectious
Diseases Society of America Guidelines." Clin Infect Dis 64(12): 1657-1662.
- Tunkel, A. R., et al. (2004). "Practice guidelines for the management of bacterial
meningitis." Clin Infect Dis 39(9): 1267-1284. 19

20. © 2016 Virginia Mason Medical Center
MKSAP Questions
20
1) A 25-year-old woman is admitted to the hospital for a 3-day history of severe
headache localizing to the back of the head. She recently had an episode of
sinusitis and has a history of sinus infections. Medical history is otherwise
unremarkable, and she takes no medications.
On physical examination, temperature is 38.9 °C (102.0 °F), blood pressure
is 134/82 mm Hg, pulse rate is 95/min, and respiration rate is 13/min. The
general medical examination is unremarkable except for mild, bilateral maxillary
sinus tenderness. On neurologic examination, she is awake and alert but
reports photophobia. There are no focal findings.
Lumbar puncture is performed.
Cerebrospinal fluid (CSF) profile:
Leukocyte count 1200/µL (1200 × 106/L) with 60% neutrophils and 40%
lymphocytes
Glucose 30 mg/dL (1.7 mmol/L)
Pressure (opening) 220 mm H2O
Protein 350 mg/dL (3500 mg/L)

21. © 2016 Virginia Mason Medical Center
Gram stain of a CSF specimen shows gram-
positive cocci in chains.
In addition to appropriate empiric antibiotics,
which of the following additional interventions is
most likely to improve outcomes?
A Dexamethasone
B Diuresis
C Maintaining head of the bed at greater
than 30 degrees
D Mannitol
21

22. © 2016 Virginia Mason Medical Center 22
Correct Answer: A
Key Point
Adjunctive dexamethasone will improve outcomes in patients with a presumptive
diagnosis of bacterial meningitis due to Streptococcus pneumoniae.
Treatment with adjunctive dexamethasone is the most likely intervention to improve
neurologic outcomes in this patient with a presumptive diagnosis of bacterial
meningitis due to Streptococcus pneumoniae. Meningitis leads to severe central
nervous system (CNS) inflammatory changes that may cause acute neurologic
changes and result in permanent, long-term neurologic damage. Neurologic sequelae
associated with pneumococcal meningitis include seizures, hearing loss, cranial nerve
deficits, and paralysis. The glucocorticoid dexamethasone decreases inflammation in
the CNS and leads to lower mortality, fewer short-term neurologic sequelae, and
decreased hearing loss in pneumococcal meningitis when used as adjunctive therapy
in developed countries. Because of these potential benefits, guidelines recommend
early dexamethasone treatment of possible or suspected pneumococcal meningitis; it
should be given approximately 15 minutes before administration of antimicrobial
agents and should be continued for the duration of antibiotic therapy.

23. © 2016 Virginia Mason Medical Center 23
A 57-year-old woman is evaluated in the emergency department for a 2-day history of
severe headache. She also reports nausea without vomiting and difficulty tolerating
bright lights. Medical history is unremarkable, and she takes no medications.
On physical examination, temperature is 38.5 °C (101.3 °F), blood pressure is
136/86 mm Hg, pulse rate is 110/min, and respiration rate is 14/min. BMI is 24. The
general medical examination is unremarkable. On neurologic examination, she shows
photophobia, and a nondilated funduscopic examination shows no papilledema. The
remainder of the examination is nonfocal.
A lumbar puncture is performed.
Cerebrospinal fluid (CSF) profile:
Leukocyte count
2235/µL (2235 × 106/L) with neutrophilic predominance
Glucose 24 mg/dL (1.3 mmol/L)
Pressure (opening) 410 mm H2O
Protein 468 mg/dL (4680 mg/L)
CSF Gram stain and culture results are pending.

24. © 2016 Virginia Mason Medical Center 24
In addition to dexamethasone, which of the
following is the most appropriate intravenous
empiric antibiotic treatment?
A Ampicillin, ceftriaxone, and vancomycin
B Ceftazidime and vancomycin
C Meropenem
D Moxifloxacin

25. © 2016 Virginia Mason Medical Center 25
Correct Answer: A
Key Point
Empiric antibiotic therapy for bacterial meningitis in the older adult should include
ampicillin, ceftriaxone, and vancomycin.
This patient should begin treatment with intravenous ampicillin, ceftriaxone, and
vancomycin. She has bacterial meningitis, and although the definitive cause has
not been determined, empiric treatment should be initiated to cover the most likely
infecting organisms. The most common causes of bacterial meningitis are
Streptococcus pneumoniae and Neisseria meningitides, which account for more
than 80% of cases. Therefore, primary empiric antibiotic therapy must adequately
cover these two organisms. Common empiric regimens include the third-
generation cephalosporins ceftriaxone or cefotaxime, which are bactericidal β-
lactams that penetrate the central nervous system (CNS) well with excellent
coverage of these organisms. One of these agents is combined with vancomycin,
which also penetrates the CNS adequately when it is inflamed and provides
coverage of possible penicillin-resistant organisms until specific identification and
sensitivities are known.

26. © 2016 Virginia Mason Medical Center
Additional antibiotic coverage is needed in patients
with risk factors for specific infections. Although
Listeria monocytogenes makes up only a small
percentage (<5%) of meningitis cases in
immunocompetent persons, the incidence increases
significantly with age. Therefore, in patients older
than 50 years, such as this patient, or persons with
impaired cell-mediated immunity, ampicillin is
added to empiric therapy because Listeria is not
adequately covered by the usual components of
empiric antibiotic regimens. Therefore, in this
patient, the combination of ampicillin, ceftriaxone,
and vancomycin provides the most appropriate
empiric coverage of the suspected pathogens while
culture results are pending. 26