Professional Documents
Culture Documents
Meningitis 2005
Meningitis 2005
MENINGITIS
Gebre K. Tseggay, MD
November 21, 2005
MAJOR CHANGES IN EPIDEMIOLOGY
OF MENINGITIS SINCE THE 1990’S
mainly due to the introduction of Hib vaccine
Dramatic drop in the number of H.influenzae meningitis cases
NEJM 1997;337:970-6
Etiology Of Bacterial Meningitis In The US
NEJM 1997;337:970-6
CHANGES IN EPIDEMIOLOGY
(cont’d)
Increase in cases of MDR- S. pneumoniae.
[Resulted in changes in empiric Rx]
Cohen & Powderly: Infectious Diseases, 2nd ed., Copyright © 2004 Mosby
CLINICAL PRESENTATION
Symptom or Sign Relative Frequency (% )
FEVER >90
HEADACHE >90
NUCHAL RIGIDITY >85
ALTERED MENTAL STATUS 80
BRUDZINSKI SIGN 50
KERNIG SIGN 50
VOMITING ~35
SEIZURES 10-30
FOCAL NEURO SIGNS 10-30
PAPILLEDEMA <1
PHOTOPHOBIA
SKIN RASH (e.g., petechia/purpura in meningococcemia)
CONFIRMATION OF SUSPECTED
BACTERIAL MENINGITIS
Lumbar puncture ASAP.
Gram Stain
Latex Agglutination (the Practice Guideline Committee does not recommend
routine use of this modality):
Does not appear to modify the decision to administer antimicrobial therapy
False-positive results have been reported
Some would recommend it for patients with a negative CSF Gram stain
result and may be most useful for the patient who has been pretreated with
antimicrobial therapy and whose Gram stain and CSF culture results are
negative.
Polymerase Chain Reaction (PCR)
Broad-based PCR may be useful for excluding the diagnosis of bacterial
meningitis, with the potential for influencing decisions to initiate or
discontinue antimicrobial therapy.
Although PCR techniques appear to be promising for the etiologic diagnosis
of bacterial meningitis, further refinements of the available techniques may
lead to their use in patients with bacterial meningitis for whom the CSF
Gram stain result is negative.
CID 2004;39:1267-1284
What Laboratory Testing May Be Helpful in Distinguishing
Bacterial from Viral Meningitis?
CSF LACTATE:
Not recommended in suspected community-acquired bacterial meningitis
May be helpful in the postoperative neurosurgical patient,
If CSF lactate concentrations are 4.0 mmol/L, initiation of empirical
antimicrobial therapy should be considered pending results of additional studies.
C-REACTIVE PROTEIN:
Normal CRP has a high negative predictive value in the diagnosis of bacterial
meningitis.
Measurement of serum CRP concentration may be helpful in patients with CSF
findings consistent with meningitis, but for whom the Gram stain is negative
and you’re considering withholding antimicrobial therapy.
INFECTIONS: NON-INFECTIOUS:
Viral meningitis (early Chemical-meningitis
phase only) (contrast…)
Some parameningeal Behcet syndrome
foci/ cerebritis
Drug –induced ( NSAIDs,
Leakage of brain Sulfa, INH, IVIG, OKT3…)
abscess into ventricle
Amebic
meningoencephalitis
TB meningitis (rarely, &
usu. only early)
BACTERIAL MENINGITIS MAY NOT ALWAYS
HAVE NEUTROPHILIC PLEOCYTOSIS?
Staphylococcus
aureus
Methicillin Nafcillin or oxacillin Vancomycin, meropenem
susceptible
Methicillin resistant Vancomycin (consider Trimethoprim-sulfamethoxazole,
adding rifampin) linezolid (consider adding rifampin)
Staphylococcus Vancomycin Linezolid
epidermidis
Enterococcus
species
Ampicillin Ampicillin + gentamicin ...
susceptible
Ampicillin resistant Vanc + gentamicin ...
Neisseria meningitidis 7
Haemophilus influenzae 7
NEJM 1997;337:970-6
(based on 248 cases from 4 states, in 1995)
ROLE OF STEROIDS
Decrease subarachnoid space inflammatory response to
abx-induced bacterial lysis
Neonates
Insufficient data to make a recommendation on the use of adjunctive
dexamethasone.
CID 2004;39:1267-1284
What Are the Indications for Repeated Lumbar Puncture
in Patients with Bacterial Meningitis?
•Not indicated routinely in patients with bacterial meningitis who have responded
appropriately to antimicrobial therapy,
• Repeated CSF analysis should be performed in:
• Any patient who has not responded clinically after 48h of appropriate antimicrobials
This is especially true for the patient with pneumococcal meningitis caused by
penicillin-or cephalosporin-resistant strains, especially for those who have also received
adjunctive dexamethasone therapy.
• Neonate with meningitis due to gram-negative bacilli should have repeated LPs
•To document CSF sterilization, because the duration of antimicrobial therapy is
determined, in part, by the result.
CID 2004;39:1267-1284
PREVENTION OF BACTERIA
MENINGITIS
Isolation of index patient
Droplet precautions
For 24 hrs after 1st dose of appropriate abx)
Post-exposure prophylaxis
Vaccination
POST-EXPOSURE PROPHYLAXIS
Candidates:
Household members
Day care center contacts
Direct exposure to pt’s oral secretion ( as in kissing,
mouth-to-mouth , intubation/ET tube management)
Index patient (if not treated w 3rd gen cephalosporins)
Regimen:
Meningococcus: Rifampin, ciprofloxacin, or ceftriaxone
Hempohilus influenzae serotype b: Rifampin.
Vaccination
Hib vaccine.
Has had major impact in incidence of pediatric Hib meningitis
Pneumococcal vaccine.
For chronically ill and elderly, & now universal use in children.
PCV-7. Use of PCV-7 for children has been an effective means of
preventing disease in older adults (JAMA. Vol. 294 No. 16, October 26,
2005 )
Meningococcal vaccine
Effective vs serotype A, C, Y, W135
Major reduction of disease in military recruits
Recommended for travelers to endemic areas.
Offered to college students, specially those residing in dormitory
A new quadrivalent vaccine (Menactra) was recently approved.
Who Should Be Vaccinated with the NEW
MENINGOCOCCAL VACCINE
(Menactra)
•Children aged 11-12 years
•Other adolescents who choose to get the vaccine to reduce their risk
"As the vaccine supply increases, CDC hopes, within three years, to recommend routine
vaccination [for] all adolescents beginning at 11 years of age," per CDC's news release
FDA and CDC Issue Alert on Menactra Meningococcal Vaccine
and Guillain Barre Syndrome
• FDA and CDC alerted consumers and health care providers to five reports of
Guillain Barre Syndrome (GBS) following administration of Meningococcal
Conjugate Vaccine (trade name Menactra).
• It is not known yet whether these cases were caused by the vaccine or are
coincidental.
• Established plan for physician visits, nurse visits, laboratory monitoring, and
emergencies
• Patient and/or family compliance with the program
• Safe environment with access to a telephone, utilities, food, and refrigerator
CID 2004;39:1267-1284
REVIEW
Most common cause overall….
CT?
Duration of Rx…
Steroids for…
Most deadly…
Isolation for…. How long?
Chemoprophylaxis
For which pathogens?
Which contacts?
What Regimen?
Vaccination?
MANAGEMENT
DO YOU WANT MORE SLIDES ON
BACTERIAL MENINGITIS??
SHUNT INFECTION
Removal of all components of the infected shunt, external drainage, +abx
COAG-NEGATIVE STAPH.:
1. If normal CSF findings, and a negative CSF culture results after externalization,
the patient can be reshunted on the 3rd day after removal.
2. If CSF abnormalities are present and a coagulase-negative staphylococcus is
isolated, 7 days of antimicrobial therapy are recommended prior to reshunting as
long as additional CSF culture results are negative and the ventricular protein
concentration is appropriate (<200 mg/dL);
3. If additional culture results are positive, abx are continued until CSF culture
results remain negative for 10 consecutive days before a new CSF shunt is placed.
STAPH. AUREUS :
10 days of negative culture results are recommended prior to reshunting .
GRAM-NEGATIVE BACILLI:
10-14 day course of antimicrobial therapy should be used, although longer durations
may be needed depending on the clinical response.
[Some experts also suggest that consideration be given to a 3-day period off antimicrobial
therapy to verify clearing of the infection prior to shunt reimplantation; although this
approach is optional, it may not be necessary for all patients].
Neisseria Meningitidis
5-15% asymptomatic nasopharyngeal colonization.
Transmission by air-droplets, kissing, sharing saliva…
Most common cause of meningitis in children and young adults , with
overall mortality rate of 3- 13%.
Causes epidemics in the “meningitis belt.”
Predisposing Factors :
Deficiencies in the terminal complement components (C5-C9)
Splenectomy
Crowding (military recruits, college dormitory, Hajj…). Tarvel.
College freshmen in dormitory>>dormitory >> freshman>>college
students overall.
Rates of meningococcal disease, by risk
group--United States, Sept. 1998--Aug. 1999
MMWR 2000,49(RR-7)1-20
Meningococcal Meningitis
Penicillin (or 3rd gen cephalosporin)
Resistance to penicillin still very rare
If penicillin used for Rx, eradication of
pharyngeal colonization of index case advisable
Duration of Rx, 7 days
Chemoprophylaxis for close contacts
Droplet isolation (for 24h after 1st dose of abx)
Streptococcus Pneumoniae
Most common cause of bacterial meningitis in the
US, with mortality rate of 19 to 26%.
Often from contiguous or distant foci of infection (e.g.,
pneumonia, otitis media, mastoiditis, sinusitis,
endocarditis, or after head trauma w CSF leak).
Predisposing factors:
Anatomic or functional asplenia, multiple myeloma,
hypogammaglobulinemia, alcoholism, malnutrition,
chronic liver or renal disease, malignancy, and diabetes
mellitus.
Pneumococcal Meningitis
Before MICs: Vancomycin + 3rd gen cephalosporin
If PSSP: Penicillin (or 3rd gen cephalosporin) alone
If PRSP(CTX-S): 3rd gen cephalosporin
If PRSP&CTX-R: Vancomycin +3rd gen cephalosp
Delayed
Seizure disorder
Focal paralysis
Subdural effusion
Hydrocephalus
Intellectual deficits
Sensorineural hearing loss
Ataxia
Blindness
Bilateral adrenal hemorrhage
Death
COMPLICATIONS of BACTERIAL
MENINGITIS
Cerebral infarction from occlusion of
inflammed vessels (focal neurologic signs, seizures,
AMS..)
Brain edema from disturbance of
cerebrovascular autoregulation, leakage of fluid
from damaged vessels, cytotoxic edema from
damaged barin cells, or dural sinus thrombosis
which impede blood drainage from brain)
Obstruction of flow of CSF (hydrocephalus)
Recommended dosages of antimicrobial agents
administered by the intraventricular route (A-
III).
Daily
intraventricular
Antimicrobial agent dose, mg
Vancomycin 5 20
Gentamicin 1 8
Tobramycin 5 20
Amikacin 5 50
Polymyxin B 5
Colistin 10
Quinupristin/dalfopristin 2 5
Teicoplanin 5 40
NOTE. There are no specific data that define the exact dose of an antimicrobial agent that should be
administered by the intraventricular route.
a Most studies have used a 10-mg or 20-mg dose.
b Usual daily dose is 1 2 mg for infants and children and 4 8 mg for adults.
c The usual daily intraventricular dose is 30 mg.
d Dosage in children is 2 mg daily.
e
RECURRENT MENINGITIS
Bacterial: Chemical:
Anatomic defect/CSF Endogenous: cranio-
leak pharyngioma, epidermid
Parameningeal infection cyst.
Immunologic (Ig def, Drugs, Behcet, SLE,
asplenia, complement Mollaret...
def...)
Hasbun et al. NEJM 2001: 345 (24): 1727
Hasbun et al. NEJM 2001: 345 (24): 1727-33
What Laboratory Testing May Be Helpful in Distinguishing Bacterial from Viral
Meningitis?
CSF Lactate
•Not recommended for patients with suspected community-acquired bacterial meningitis
•However, measurement of CSF lactate concentrations was found to be superior to use of the ratio of
CSF to blood glucose for the diagnosis of bacterial meningitis in postoperative neurosurgical patients,
in which a CSF concentration of 4.0 mmol/ L was used as a cutoff value for the diagnosis…
Therefore, 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.
C-reactive Protein
Measurement of serum CRP concentration may be helpful in patients with CSF findings consistent
with meningitis, but for whom the Gram stain result is negative and the physician is considering
withholding antimicrobial therapy, on the basis of the data showing that a normal CRP has a high
negative predictive value in the diagnosis of bacterial meningitis.
Procalcitonin
At present, because measurement of serum procalcitonin concentrations is not readily available in
clinical laboratories, recommendations on its use cannot be made at this time (C-II).
Polymerase Chain Reaction
In patients who present with acute meningitis, an important diagnostic consideration is whether the
patient has enteroviral meningitis. Rapid detection of enteroviruses by PCR has emerged as a valuable
technique that may be helpful in establishing the diagnosis of enteroviral meningitis.
IMPACT OF PCV-7