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EPIDEMIOLOGY OF

BACTERIAL MENINGITIS, US, 1996

 Worldwide 1.2 million cases


each year
 10th most common cause of
infectious death
 135,000 deaths annually
 Neurologic sequelae common

Schuchat A, et al. NEJM 1997;337:970-6


Swartz M, NEJM 2004
MANAGING ACUTE MENINGITIS:
HISTORY
 Duration/pace of symptoms
 Recent exposure to someone with meningitis
 Tick exposure
 Rash (viral exanthems, ulcerations, petechial or palpable purpura)
 A recent infection (especially respiratory or otic infection)
 A history of recent head trauma, otorrhea or rhinorrhea
 Recent travel, particularly to areas with endemic meningococcal disease
such as sub-Saharan Africa
 A history of injection drug use
 HIV serostatus, sexual history
 Any other immunocompromising conditions
 Recent use of antibiotics
 Serious antibiotic allergies
 TB exposure
 Pregnancy
Nosocomial

 Risk Factors
 Head trauma
 Neurosurgery
 CSF leak
 VP shunt, hardware
 Underlying illness (DM, luekemia, AIDS, cirrhosis)
 Pathogens
 Staph aureus (MSSA and MRSA)
 Enteric GNRs (E coli, Klebsiella)
Polymicrobial gram negative meningitis: think
Strongyloides hyperinfection syndrome
 Mortality
 Up to 35%
CLINICAL FINDINGS IN COMMUNITY-
ACQUIRED BACTERIAL MENINGITIS
Symptom US, MGH Netherlands
1962-88 (296) 1998-92 (N=696)
Fever, neck stiffness &  MS 67% 44%
1 sign present: 99% (fever, neck 99% (fever, HA, neck
stiffness,  MS) stiffness,  MS)
2 signs present NA 95% (as above)
Fever 95% 77%
Neck stiffness 88% 83%
Headache NA 87%
Rash 11%* 26%

22/30 N. menigitidis, rash also present with S. pneumoniae, H. influenzae, negative culture
CSF FINDINGS IN COMMUNITY-ACQUIRED
ACUTE BACTERIAL MENINGITIS, MGH

 Opening pressure (mm H20)  Percent PMNs


 0-139 9%  0-19 2%
 140-299 52%  20-79 19%
 300-399 20%  >80 79%
 >400 19%  Glucose mg/dL
 WBC per mm3  <40 50%
 0-99 13%  Gram stain
 100-4999 59%  Positive 60%
 5000-9999 15%
 Culture
 >10,000 13%
 Positive 73%
Neurologic Complications

 Systemic  Neurologic
 Septic shock  Impaired mental status
 ARDS  Increased ICP, herniation
 DIC  Seizures (25%)
 Septic or reactive arthritis  CN palsies, focal neurologic
 Death (25%) deficits
 Older age  Sensorineural hearing loss
 Obtundation at presentation  Neurocognitive/intellectual
 Seizures within 24 hours impairment
 Strep pneumonia
TREATMENT:
GENERAL GUIDELINES

 Use bactericidal drugs


 Cover potential for resistance
 S pneumonia: Vanc (20% PCN-R, 5% CTX-R)
 Neisseria mening: Ceftriaxone
 Use highest safe dose
 Use antibiotics that penetrate CNS
 Provide all antibiotics by intravenous route
 If bacteristatic antibiotic is used (e.g., doxycycline) initiate after
bactericidal drug
 Ideally initiate antibiotics within 30 minutes for acute bacterial
meningitis
TREATMENT:
EMPIRIC THERAPY

 Age 18-50
 S. pneumoniae, N. meningitidis; much less likely H. influenzae,
L. monocytogenes, Grp B streptococcus
 Ceftriaxone 2 mg IV Q12 hr plus vancomycin 1 gm IV Q12 hr*
 Consider adding doxycycline 100 mg IV Q12 hr (RMSF season)
 Acyclovir if HSV or VZV suspected
 Age >50
 S. pneumoniae, N. meningitidis, L. monocytogenes; less often
Grp B streptococcus, H. influenzae, GNR
 Above plus ampicillin 2 gm IV Q4 hr
 Consider adding doxycycline 100 mg IV Q12 hr (RMSF season)
 Acyclovir if HSV or VZV suspected
30-45 mg/kg per day divided every 8-12 hours
TREATMENT:
EMPIRIC THERAPY

 Impaired cellular immunity


 L. monocytogenes, Gram-negative bacilli
 Ceftazidime* 2 g IV Q8 hr plus vancomycin 1 gm IV Q12 hr plus
ampicillin 2 mg IV Q4 hr
 Consider adding doxycycline 100 mg IV Q12 hr (RMSF season)

 Nosocomial meningitis
 Coagulase negative staphylococcus, S. aureus, Gram-negative
bacilli, streptococci
 Ceftazidime* 2 g IV Q8 hr plus vancomycin 1 gm IV Q12 hr
* Use ceftazidime instead of ceftriaxone for improved coverage of P. aeruginosa
TREATMENT:
PENICILLIN-ALLERGIC PATIENT

Options
 Replace ceftriaxone or ceftazidime with meropenem (carbapenem
approved for meningitis) – small risk of cross reactivity
 Coverage: MSSA, streptococci, penicillin-susceptible pneumococci,
meningococcus, GNRs, P. aeruginosa
 Replace ceftriaxone or ceftazidime with aztreonam (monobactam) –
low risk of cross reactivity (no coverage for pneumococcus)
 Coverage: Meningococcus, GNRs, P. aeruginosa
 Replace ceftriaxone with chloramphicol (or moxifloxacin)
 Coverage chloramphenicol: Streptococci, pneumococci, RMSF,
meningococcus, H. influenzae
DURATION OF THERAPY

 Neisseria meningitidis 7 days


 Hemophilus influenzae 7 days
 Streptococcus pneumoniae 10-14 days
 Streptococcus agalactiae 14-21 days
 Aerobic GNR 21 days
 Listeria monocytogenes >21 days
ETIOLOGIES OF ACUTE MENINGITIS
IN HIV INFECTED PATIENTS

 Usual bacterial agents: S. pneumoniae, N. meningitidis,


H. influenza
 Other bacteria: TB, Syphilis, L. monocytogenes
 Viruses (acute HIV, CMV, HSV, VZV)
 Fungi: Cryptococcus (most common), Histoplasma,
Coccidioides
CASE FATALITY RATE,
BACTERIAL MENINGITIS

Pathogen MGH (N=493) 4 states Netherlands


1962-88 (N=248) 1995 (N=696) 1998-02
S. pneumoniae 25% (28%)* 21% 21%
N. meningitidis 10% (10%) 3% 7%
H. Influenza 11% (11%) 6% ---
L. monocytogenes 21% (32%) 15% ---
GNR 23% (36%) --- ---
S. aureus 28% (39%) --- ---
Streptococci 17% (25%) 7% (GBS) ---
Enterococcus 25% (50%) ---- ---
NEJM 1993;328:21-28 (* total mortality); NEJM 1997;337:970-6; NEJM 2004;351:1849-59
MANAGEMENT OF MENINGITIS:
KEY CLINICAL DECISIONS

 Clinical presentation
 Meningitis: Viral, bacterial, fungal, mycobacterial
 Encephalitis (abnl brain function—motor/sensory, change in
MS, personality, speech/movement): Arboviruses, HSV
 Onset
 Acute: S. pneumoniae, N. meningitidis
 Chronic: Fungal, mycobacterial
 Recurrent: S. pneumoniae
 Host
 Normal
 Immunocompromised: HIV, organ transplant, steroids
Aseptic Meningitis

 Definition: signs/sx/laboratory evidence of meningitis with


negative standard bacterial cx
 Most common cause: enteroviral (summer, coxsackie, echovirus,
nonpolio enteroviruses, dx by PCR)
 Other etiologies: spirochetes (lyme, RMSF, syphilis),
mycobacteria (TB), mycoplasma, drugs (NSAIDS, sulfa), cancer,
parameningeal focus, autoimmune (neurosarcoid, behcet’s, SLE)
 Viruses: primary HSV, VZV, HHV6, CMV, acute HIV, mumps,
LCM, West Nile virus, adenovirus
 Parasites: Angiostrongylus cantonensis (rat lungworm, SE Asia),
CSF eosinophilia
 Recurrent aseptic (Mollaret’s) meningitis: HSV-2
ED MANAGEMENT:
SUSPECTED MENINGITIS

 Initiate droplet precautions (N. meningitidis)


 Appropriate resuscitation (fluids, airway, etc.)
 Blood cultures x 2
 LP within 30 minutes
 If LP cannot be performed within 30 minutes initiate empiric
antibiotics
 Consider dexamethasone for bacterial meningitis, especially if
pneumococcal disease suspected or demonstrated
 CT with contrast or MRI with gadolinium if CNS mass lesion
suspected
INDICATIONS FOR BLOOD CULTURES

 Before the use of parenteral or systemic antimicrobial therapy in


ANY hospitalized patient with fever (>38 oC) combined with
leukocytosis or leukopenia
 Systemic and localized infections including suspected acute
sepsis, meningitis, osteomyelitis, arthritis, acute untreated
bacterial pneumonia, and fever of unknown origin in which
abscesses or other bacterial infection is possible.
 Test of cure: 48-72 hours after initiation of therapy for bacteremia
or fungemia
DOs AND DON’Ts OF
OBTANING BLOOD CULTURES

 Always obtain using strict aseptic technique to prevent


contamination (i.e., a false positive result)
 Label bottles properly (name, hospital number)
 Fill bottles with proper volume
 Adults: 10 mL per bottle
 Children: 0.5-5 mL per bottle (based on weight)
 Obtain at least 2 blood cultures
 Yield related to number of cultures obtained
 Allows assessment of skin commensals contaminating cultures
DOs AND DON’Ts OF
OBTANING BLOOD CULTURES

 Obtain cultures from different sites (or same site


separated by at least 30 min)
 Never split blood obtained at single time from single site into
multiple blood culture sets
 Avoid femoral site (if possible)
 Avoid obtaining blood through non-intact skin (if possible)
 Obtain via an arterial line only if no other site available
DOs AND DON’Ts OF
OBTANING BLOOD CULTURES

 Do not obtain blood via a peripheral catheter


 Rate of contamination 9.1% (via catheter) vs 2.8% (via
peripheral stick) {Weinstein M. CID 1996;23:40}
 Do not change needles between venipuncture and
inoculation of blood culture bottles
CONTAMINATION AND TRUE INFECTION
RATE OF BLOOD CULTURES, UNC
Total contamination rate ED contamination rate Total true positives

9.00%
8.00%
7.00%
6.00%
5.00%
4.00%
3.00%
2.00%
1.00%
0.00%
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May

2007 2008
ISOLATION FOR
AIRBORNE/DROPLET DISEASES

Airborne isolation Droplet isolation


 Private room, direct out  Private room
exhausted air, negative  Mask for entering room
pressure  Diseases: invasive
 N95 respirator for meningococcal infection,
entering room influenza, pertussis
 Diseases: TB, measles,
varicella
Any healthcare worker can initiate isolation
Only a physician can discontinue isolation
Post Exposure Prophylaxis

 Regimen options:
 Ciprofloxacin 500 mg PO x 1
 Ceftriaxone 250 mg IM x 1 (children, pregnant women)
 Rifampin 600 mg PO 2x/day for 2 days (resistance described)
 Definition of exposure
 Droplet spread disease
 Close contact with respiratory secretions (mouth-to-mouth
resuscitation, intubation, nasotracheal suctioning)
IMPACT OF
DELAYED ANTIBIOTIC THERAPY

 Retrospective study of 269 patients with community


acquired meningitis (Aronin SI, et al. Ann Intern Med 1998;129:862-9)
 Indicators of poor outcome (death, neurologic deficit): Altered
mental status, hypotension and/or seizures
 Delay in therapy associated with worse outcome if patient
developed all 3 above signs
 Retrospective study of 123 patients with community
acquired meningitis (Proulx N, et al. QJM 2005;98:291-98)
 OR for mortality: Door-to-antibiotics >6 hr, 8.4; afebrile at
presentation, 39.4; severely impaired mental status, 12.6
IMPACT OF
DELAYED ANTIBIOTIC THERAPY

 Prospective study of 156 patients with pneumococcal


meningitis found a delay of >3 hours was independently
associated with 3-month mortality (Crit Care Med 2006;34:2758)
REASONS FOR OBTAINING CSF

 Allows exclusion of meningitis*


 Provides diagnosis of meningitis*
 Allows specific etiologic diagnosis of acute bacterial
meningitis (e.g., S. pneumoniae, N. meningitidis)
 May make alternative diagnosis (e.g., cryptococcus, HSV)
 Allows susceptibility testing of isolate (esp. important for
S. pneumoniae)
 May have prognostic significance
Rarely CSF may be normal in early bacterial meningitis
EMPIRIC DIAGNOSIS
BASED ON CSF PROFILE

Pattern PMN predominant Lymphocytic Lymphocytic


Low glucose Normal glucose Low glucose
Spectrum Bacterial Parameningeal Mycobacterial
Viral Fungal
Pathogens S. pneumonia, Enteroviruses M. tuberuculosis
N. meningitidis Brain abscess Endemic fungi
Mumps, LCM
Non- Sulfa drugs Auto-immune
infectious Non-steroidals diseases
EFFECTS OF
PRIOR ANTIBIOTICS ON CSF FINDINGS

 A short period of antibiotic therapy prior to LP does not


change cerebrospinal fluid (CSF) white blood cell count,
protein, or glucose
 The yield of CSF gram stain and culture may be reduced
by a short period of antibiotic therapy, but these tests
often remain positive
EFFECTS OF
PRIOR ANTIBIOTICS ON CSF FINDINGS

 Retrospective study of 1,316 patients; 54.6% had received antibiotics


before presentation (Geiseler PJ, et al. RID 1980;2:725)
 No significant differences in CSF WBC, glucose, or protein concentrations
for S. pneumoniae, H. influenzae, N. menigitidis
 Significantly lower frequency of positive blood and CSF cultures for all 3
organisms, esp. N. meningitidis
 Retrospective study of 128 patients (Kanegaye JT. Pediatr 2001;1081:169)
 3/9 patients with N. meningitis were sterile within 1 hour (1 15 min) and all
negative by 2 hours
 Pneumococcal disease: first negative at 4.3 hours, 5/7 negative at 4-10
hours
MANAGEMENT ISSUE
CT or MRI before LP
INDICATIONS FOR CT/MRI BEFORE LP

 Immunocompromised state (eg, HIV infection,


immunosuppressive therapy, active cancer, BMT or
organ transplantation)
 History of CNS disease (mass lesion, stroke, or focal
infection)
 New onset seizure (within one week of presentation)
 Papilledema
 Abnormal level of consciousness
 Focal neurologic deficit

Tunkel AR, et al. CID 2004 39:1267-84 (IDSA)


EVALUATING RISK OF LP WITHOUT CT

 Reports of harm (herniation post-LP) only case reports with


temporal relationship (Ann Neurol 1980;7:524, Pediatr 2003;112:e174, J
Neurol Psychopathol 1933;14:116)
 Even with focal CNS lesions, herniation post-LP uncommon
 200 patients with increased ICP from brain tumor; no adverse
effects of LP (Res Nerv Ment Dis Proc 1927;8:422)
 103 patients with increased ICP; death during hospitalization in 4,
no herniation (J Neurol Psychoopath 1933;14:116)
 Even with papilledema LP almost always safe (J Mt Sinai Hosp NY
1956;23:808, Neurol 1959;9:290)
EVALUATING RISK OF LP WITHOUT CT

 Among patients dying with meningitis, herniation is a


common cause of death (even with a normal LP herniation
may occur) – MGH 8/27 autopsied patient had herniation
 Prediction rules for abnormal CT have been proposed
(Hasbun R, et al. NEJM 2001;345:1727)
 235 patients with CT before LP: 5% had mass effect
 Age >60 years, seizure within 7 days, immunocompromised, hx
of CNS disease, altered mental status, gaze or facial palsy,
inability to answer 2 questions or follow 2 commands, visual
field abnormalities, arm or leg drift, or abnormal language
MANAGEMENT ISSUE
Use of dexamethasone
Tunkel AR, et
al. CID 2004;
39:1267-84
Case Answers

 HIV Elisa negative, HIV RNA PCR negative


 HSV, VZV pcr negative
 Gram stain, culture negative
 Lyme ab negative, RPR/VDRL negative
 Enteroviral PCR of stool and CSF: positive
 Rash: viral exanthem
 EKG: myocarditis
 Management: supportive
GENERAL REFERENCES

 Durand ML, et al. Acute bacterial meningitis in adults. NEJM


1993;328:21-28.
 Van de Beek, D, et al. Community-acquired bacterial meningitis
in adults. NEJM 2006;354:44-53.
 Weisfelt M, et al. Bacterial menigitis: a review of effective
pharmacotherapy. Expert Opin 2007;8:1493-1504.
 Fitch MT, et al. Emergency diagnosis and treatment of adult
meningitis. Lancet ID 2007;7:191-200.
 Fitch MT, et al. Emergency department management of
meningitis and encephalitis. ID Clin NA 2008;22:33-52.
 Tunkel AR, et al. Practice guidelines for the management of
bacterial meningitis. Clin Infect Dis 2004;39:1267-84
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