Transcript Diagnosis

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Meningitis – inflammation of the meninges
Encephalitis – inflammation of the brain
parenchyma
Meningoencephalitis – inflammation of brain +
meninges
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Meningitis is a clinical syndrome characterized
by inflammation of the meninges
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There are numerous infectious and
noninfectious causes of meningitis
(common noninfectious causes eg, medications
and carcinomatosis)
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may be classified as acute or chronic
 Acute meningitis -hours to several days
 Chronic meningitis -at least 4 weeks.
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acute bacterial meningitis
 2.acute aseptic meningitis
 3.chronic meningitis
 4. other (depend on specific pathogen);
fungal meningitis, parasitic meningitis i.e
Three major pathways which an infectious agent gains
access to the CNS and causes meningeal disease
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Hematogenous (eg, from bacteremia, viremia, fungemia)
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Retrograde neuronal pathway (eg, Naegleria fowleri,
rabies, HSV, VZV)
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Direct contiguous spread (eg, sinusitis, otitis media,
congenital malformations, trauma, direct inoculation during
intracranial manipulation)
Fever , malaise
 Headache
 nausea, vomiting
 photophobia
 Hyperirritability
 neck stiffness
 changes in mental status
 Seizure occur in approximately 30% of
patients
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meningeal irritation sign
 Nuchal rigidity, Kernig-, Brudzinsky
signs,
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Sign of increase ICP
◦ Papilledema
◦ Cushing’s triad
 Bradycardia
 Hypertension
 Irregular respiration
◦ Changes in pupils
◦ LR palsy
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Focal neurological deficit
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Atypical presentation may be observed in
certain groups
◦ Elderly, especially with underlying comorbidities (eg,
diabetes, renal and liver disease), may present with
lethargy and an absence of meningeal symptoms.
◦ Patients with neutropenia may present with subtle
symptoms of meningeal irritation.
◦ Other ; immunocompromised hosts, including organ
and tissue transplant recipients and patients with HIV
and AIDS
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patients with aseptic meningitis syndrome usually
appear clinically nontoxic with no vascular instability.
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sexual contact and high-risk behavior:
HSV meningitis is associated with primary genital
HSV infection and HIV infection
exposure to a patient with a similar illness is an
important epidemiological clue when determining
etiology (eg, meningococcemia).
intake of unpasteurized milk predisposes to
brucellosis and L monocytogenes infection.
Animal contacts rabies (LCM) virus Leptospira
History of neurosurgery eg, ventriculoperitoneal
shunt cochlear implants
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Sinusitis or otitis suggests direct extension into the
meninges, usually with S pneumoniae and H
influenzae
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Rhinorrhea or otorrhea suggests a CSF leak from a
basilar skull fracture, with meningitis most commonly
caused by S pneumoniae.
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petechiae are seen in meningococcal disease with or
without meningitis
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The presence of a murmur suggests infective
endocarditis with secondary bacterial seeding of the
meninges
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Hepatosplenomegaly and lymphadenopathy
suggest a systemic disease, including viral (eg,
mononucleosislike syndrome in EBV, CMV, and
HIV) and fungal (eg, disseminated
histoplasmosis) disease.
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Vesicular lesions in a dermatomal distribution
suggest varicella-zoster virus. Genital vesicles
suggest HSV-2 meningitis
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the widespread use of HIB vaccine has decreased the incidence
of HIB meningitis by more than 90% the median age of patients
shifting from younger than 2 years to 25 years
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◦ gram-positive cocci, colonize at human nasopharynx.
◦ most common bacterial cause of meningitis, accounting for 47% of
cases with mortality rates 19-26%
◦ Mechanism: hematogenous or direct extension from sinusitis or
otitis media
◦ Risk factor
 basilar skull fracture and CSF leak.
 Patients with hyposplenism or splenectomy
 hypogammaglobulinemia, multiple myeloma
 glucocorticoid treatment
 diabetes mellitus, renal insufficiency, alcoholism,
malnutrition, and chronic liver disease
◦ gram-negative diplococci that is carried in the
nasopharynx (10-15%)
◦ leading cause of bacterial meningitis in children and
young adults, accounting for 59% of cases
◦ Meningococcal disease: purulent conjunctivitis,
septic arthritis, sepsis +/- meningitis
◦ Risk factors:
 household crowding ,college dormitories , military
facilities
 chronic medical illness
 corticosteroid use
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small, pleomorphic, gram-negative coccobacilli
frequently found as normal flora in the upper respiratory
tract of humans
can spread by airborne droplets or direct contact with
secretions
Meningitis is caused by the encapsulated type B strain
It primarily affects infants younger than 2 years. Its
isolation in adults suggests the presence of an underlying
medical disorder, including sinusitis, otitis media,
alcoholism, CSF leak following head trauma,
hyposplenism and hypogammaglobulinemia
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◦ small gram-positive bacillus
◦ one of the highest mortality rates (22%).
◦ Most human cases appear food-borne: coleslaw, milk,
cheese i.e
◦ Risk factor:
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infants and children, elderly (>60 y)
pregnant women
Alcoholism
Patients with CMI defect
immunocompromised
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most common infectious syndrome affecting
the CNS
acute onset of meningeal symptoms, fever,
and cerebrospinal pleocytosis (usually
prominently lymphocytic)
with negative bacterial microbiologic data
Most episodes are caused by a viral pathogen
but they can also be caused by bacteria,
fungi, or parasites
Virus
 HERPES (HSV, HZV, EBV, CMV),
 ENTERO (Echo,Coxakie,Polio,Enterovirus
68-71 etc.)
 ARBO (JEV, Tick-bite encephalitis virus)
 Adenovirus
 LCMV
 HIV
 Rabies virus
 Mump ,Measles
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VZV and CMV
◦ causes meningitis in immunocompromised hosts,
especially AIDS and transplant recipients
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Lymphocytic choriomeningitis virus(LCMV)
◦ transmit by aerosols and direct contact with rodents.
◦ may be associated with orchitis, arthritis, myocarditis,
and alopecia.
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HIV
◦ Aseptic meningitis may be the presenting symptom in a
patient with acute HIV infection. This usually is part of
the mononucleosislike acute seroconversion
phenomenon.
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Mump
◦ Meningitis usually follows the onset of parotitis, which
clinically resolves in 7-10 days
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Bacteria
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Partially-treated bacterial meningitis
L monocytogenes
Brucella species
Rickettsia rickettsii
Ehrlichia species
Mycoplasma pneumoniae
B burgdorferi
Treponema pallidum
Leptospira species
Mycobacterium tuberculosis
Nocardia species
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Parasites
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N fowleri
Acanthamoeba species
Balamuthia species
Angiostrongylus cantonensis
G spinigerum
Baylisascaris procyonis
S stercoralis
Taenia solium (cysticercosis)
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Fungi
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Cryptococcus neoformans
C immitis
B dermatitidis
H capsulatum
Candida species
Aspergillus species
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constellation of signs and symptoms of
meningeal irritation associated with CSF
pleocytosis that persists for longer than
4 weeks.
◦ acid-fast bacilli
◦ spread through airborne, droplet
◦ The presentation may be acute, but the classic
presentation is subacute and spans weeks
◦ Patients generally have a prodrome of fever of
varying degrees, malaise, and intermittent headaches
◦ Patients often develop central nerve palsies (III, IV, V,
VI, and VII), suggesting basilar meningeal
involvement
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clinical staging of meningeal tuberculosis is
based on neurologic status
◦ Stage 1 - no change in mental function with no
deficits and no hydrocephalus
◦ Stage 2 - confusion and evidence of neurologic
deficit
◦ Stage 3 - stupor and lethargy
Always consider tuberculous meningitis in
the differential diagnoses of patients with
aseptic meningitis or chronic meningitis
syndromes
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T pallidum
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modes of transmission:
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sexual contact
direct contact with an active lesion
passage through the placenta
blood transfusion (rare)
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Three stages of disease are described, and involvement
of the CNS can occur during any of these stages.
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Syphilitic meningitis usually occurs during the primary
or secondary stage. Its presentation is similar to other
agents of aseptic meningitis
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Other CNS syphilitic syndromes include
◦ meningovascular syphilis
◦ parenchymatous neurosyphilis
◦ gummatous neurosyphilis
and the symptoms are dominated by focal
syphilitic arteritis (ie, focal neurologic symptoms
associated with signs of meningeal irritation)
C. neoformans
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an encapsulated yeast-like fungus that found in
high concentrations in aged pigeon droppings
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50-80% of cases occur in immunocompromised
hosts
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The infection is characterized by the gradual
onset of symptoms, the most common of which
is headache.
The onset may be acute, especially among
patients with AIDS
Free-living amoebas (ie, Acanthamoeba, Balamuthia,Naegleria)
◦ infrequent but often life-threatening illness
◦ N fowleri
is the agent of primary amebic
meningoencephalitis (PAM)
◦ Infection occurs when swimming or playing in the
contaminated water
◦ invade the CNS through the nasal mucosa and cribriform
plate.
◦ PAM occurs in 2 forms.
 an acute onset of high fever, photophobia,
headache, and change in mental status, similar to
bacterial meningitis with involvement of the
olfactory nerves sensation. Death occurs in 3 days in
patients who are not treated.
 subacute or chronic form, is an insidious onset of
low-grade fever, headache, and focal neurologic
signs.
Acanthamoeba and Balamuthia cause
granulomatous amebic encephalitis, which spreads
hematogenously from the primary site of infection
(skin or lungs)
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A cantonensis
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G spinigerum
◦ cause eosinophilic meningitis (pleocytosis with >10%
eosinophils)
◦ acquire the infection by ingesting raw mollusks.
◦ present with nonspecific and self-limited abdominal pain
caused by larval migration into the bowel wall.
◦ On rare occasions, the larva can migrate into the CNS and
cause eosinophilic meningitis
◦ cause eosinophilic meningoencephalitis
◦ acquire the infection following ingestion of undercooked
infected fish and poultry.
Encephalitis
 Brain Abscess
 Noninfectious meningitis, including medicationinduced meningeal inflammation
 Meningeal carcinomatosis
 Stroke
 CNS vasculitis
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Lumbar puncture for CSF examination is
urgently warranted in individuals in
whom meningitis is clinically suspected
 CSF for
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◦ Chemistry (glucose & protein)
◦ cell count & diff
◦ Gram stain ,AFB stain
◦ Culture for pathogens
◦ Other : India ink ,serology ,PCR ,Ag
Identification ,cytology i.e
Between L3-L4(iliac crest level) or L4-L5
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Contraindications:
◦ increase risk of herniation(suspected space
occupying lesion in CNS)
◦ Skin & soft tissue infection at area of tap
◦ Bleeding disorder
◦ Respiratory distress (positioning)
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Complications
◦ Cerebral herniation
◦ Postdural puncture headache
◦ Traumatic tap ,Spinal trauma
 CBC
 BS
 Anti-HIV
 H/C
 cultures
from other possible sites
of infection
CT or MRI of the brain
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indicated in patients with
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focal neurologic deficit
increased ICP
suspicious for space-occupying lesions
suspected basilar fracture
diagnosis is unclear
Helpful in the detection of CNS complications of
bacterial meningitis, such as hydrocephalus,
cerebral infarct, brain abscess, subdural empyema,
and venous sinus thrombosis
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Bacterial meningitis is a neurological
emergency that is associated with significant
morbidity and mortality. The initiation of
empiric antibacterial therapy is therefore
essential for better outcome
usually based on the known predisposing
factors and/or initial CSF Gram-stain results.
delays in instituting antimicrobial treatment
in individuals with bacterial meningitis could
lead to significant morbidity and mortality
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penicillins, certain cephalosporins (ie, thirdand fourth-generation cephalosporins), the
carbapenems, fluoroquinolones, and rifampin
provide high CSF levels
Once the pathogen has been identified and
antimicrobial susceptibilities determined, the
antibiotics may be modified for optimal
targetted treatment
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Recommended Empiric Antibiotics According to Predisposing
Factors for Patients With Suspected Bacterial Meningitis
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Recommended Empiric Antibiotics for Patients With
Suspected Bacterial Meningitis and Known CSF Gram
Stain Results
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Specific Antibiotics and Duration of Therapy for
Patients With Acute Bacterial Meningitis
Agent
Dosage
Ampicillin
12 g/day q 4h
Cefepime
6 g/day q 8h
Cefotaxime
12 g/day q 4h
Ceftriaxone
4 g/day q 12h
Ceftazidime
6 g/day q 8h
Gentamicin
7.5 mg/kq/day q 8h
Meropenem
3 g/day q8h
Metronidazole
1500-2000 mg/day q 6h
Nafcillin
9-12 g/day q 4h
Penicillin G
20-24 million U/day q 4h
Vancomycin
2 g/day q 2h
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The use of corticosteroids such as dexamethasone as
adjunctive treatment was significantly associated with
a reduction in case-fatality rate and neurologic
sequelae
Strongly consider in patients with certain types of
bacterial meninigitis, such as H influenzae, tuberculous,
and pneumococcal meningitis
should be administered prior to or during the
administration of antimicrobial therapy
May associate with decreased penetration into the CSF
of some antimicrobials, such as vancomycin
Dexamethasone (0.15 mg/kg per dose q6h for 2-4 d)
◦ Most viral meningitis are benign and self-limited.
Often, they require only supportive care and do not
require specific therapy
◦ In certain instances, specific antiviral therapy may be
indicated, if available
 Acyclovir (10 mg/kg IV q8h) for HSV-1 and HSV-2
 Ganciclovir (induction dose of 5 mg/kg IV q12h,
maintenance dose of 5 mg/kg q24h) and foscarnet
(induction dose of 60 mg/kg IV q8h, maintenance dose
of 90-120 mg/kg IV q24h) for CMV meningitis in
immunocompromised hosts.
◦ Instituting highly active antiretroviral therapy (HAART)
may be necessary for patients with HIV meningitis
that occurs during an acute seroconversion syndrome
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The demonstration of the acid-fast in the CSF
is difficult and usually requires a large volume
of CSF
The culture for Mycobacterium usually takes
several weeks and may delay definitive
diagnosis.
Nucleic acid amplification forM tuberculosis
have the advantage of a rapid, sensitive, and
specific
The need for mycobacterial growth in cultures
remains because this offers the advantage of
performing drug susceptibility assays.
◦ Isoniazid (INH) and pyrazinamide (PZA) attain good
CSF levels (approximate blood levels). Rifampin (RIF)
penetrates the BBB less efficiently but still attains
adequate CSF levels.
◦ use the combination of the first-line drugs (ie, INH,
RIF, PZA, ethambutol, streptomycin.
◦ The dosage is similar to what is used for pulmonary
tuberculosis (ie, INH 300 mg qd, RIF 600 mg qd, PZA
15-30 mg/kg qd, ethambutol 15-25 mg/kg qd,
streptomycin 7.5 mg/kg q12h).
◦ A treatment duration of 12 months is the minimum,
and some experts suggest a duration of at least 2
years.
◦ The use of corticosteroids is indicated for individuals
with stage 2 or stage 3 disease (ie, patients with
evidence of neurologic deficits or changes in their
mental function). The recommended dose is 60-80
mg/d, which may be tapered gradually during a span
of 6 weeks.
Diagnosis : identification of the pathogen in the CSF
 C neoformans culture from CSF
 India ink preparation : sensitivity of only 50%, but
highly diagnostic if positive
 CSF cryptococcal antigen : sensitivity of greater than
90%
 blood cultures and serum cryptococcal antigen to
determine if cryptococcal fungemia is present
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Induction therapy: amphotericin B (0.7-1
mg/kg/d IV) for at least 2 weeks
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Consolidation therapy: fluconazole (400 mg/d
for 8 wk). Itraconazole is an alternative
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Maintenance therapy: Long-term antifungal
therapy with fluconazole (200 mg/d)
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In case of increased ICP. Make an effort to
reduce such pressure by repeated lumbar
puncture, a lumbar drain, or shunt
 Induction/consolidation: Administer amphotericin
B (0.7-1 mg/kg/d) plus flucytosine (100
mg/kg/d) for 2 weeks. Then, administer
fluconazole (400 mg/d) for a minimum of 10
weeks.
 A lumbar puncture is recommended after 2 weeks
to document sterilization of the CSF. If the
infection persists, longer therapy is
recommended. Solid organ transplant recipients
require prolonged therapy.
◦ C. immitis
 oral fluconazole (400 mg/d) or
 Itraconazole (400-600 mg/d)
 Duration of treatment usually is life long.
◦ H capsulatum
 Amphotericin B at 0.7-1 mg/kg/d to complete a total
dose of 35 mg/kg
 Fluconazole (800 mg/d) for an additional 9-12 months
may be used to prevent relapse.
◦ Candida species
 amphotericin B (0.7mg/kg/d)+/- Flucytosine (25 mg/kg
qid)
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The CSF is characterized by mild lymphocytic pleocytosis.
elevated CSF protein levels & decreased glucose levels may
be observed in 10-70% of cases.
Demonstrate the spirochete by using dark-field or phasecontrast microscopy on specimens collected from skin
lesions (eg, chancres and other syphilitic lesions).
CSF VDRL : sensitivity of 30-70% (a negative result does not
rule out syphilitic meningitis) and a high specificity (a
positive test result suggests the disease).
serologic tests to detect syphilis : VDRL test ,FTA-Abs ,TPHA
 penicillin G (2-4 million U/d IV q4h) for 10-14 days,
often followed with benzathine penicillin G 2.4 million
U IM.
 Alternative : administer procaine penicillin G (2.4
million U/d IM) plus probenecid (500 mg PO qid) for
14 days, followed by IM benzathine penicillin G (2.4
million U).
 Repeat CSF examination : cell count , serologic titers
 Because penicillin G is treatment of choice, patients
who are allergic to penicillin should undergo penicillin
desensitization
increased intracranial pressure (ICP)
 venous sinus thrombosis
 subdural empyema
 brain abscess
 cranial nerve palsies
 cerebral infarction result from impaired
cerebral blood flow
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Hearing impairment
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Obstructive hydrocephalus
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Brain parenchymal damage
Monitor the clinical course & response
to medical treatment
 surveillance for the development of
complications
 Seizure precautions are indicated,
especially for patients with impaired
mental function
 Proper isolation precautions in cases of
invasive meningococcal disease
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Monitor patients for potential adverse
effects of medications, such as
hypersensitivity reactions, cytopenia, or
drug toxicity
 Drug-level monitoring for some
antibiotics such as vancomycin and
aminoglycosides
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Capable of transmitting organism up to 24
hours after initiation of appropriate
therapy
Droplet precautions x 24 hours, then no
isolation
Incubation period 1 - 10 days, usually <4
days
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Persons who have had “intimate contact”
w/ oral secretions prior & during 1st 24 h
of antibiotics
“Intimate contact” – 300-800x risk
(kissing, eating/ drinking utensils, mouth-to-mouth,
suctioning, intubating)
Treat within 24 hours of exposure
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Rifampin
◦ Urine, tears, soft contact lenses orange;
OCP’s ineffective
◦ <1 mo 5 mg/kg PO Q 12 x 2 days
◦ >1 mo 10 mg/kg (max 600 mg) PO Q 12 x
2 days
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Ceftriaxone
◦ 12 y 125 mg IM x 1 dose
◦ >12 y 250 mg IM x 1 dose
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Ciprofloxacin
◦ 18 y 500 mg PO x 1 dose
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viral meningitis usually have a good prognosis for recovery.
The prognosis is worse for patients at the extremes of age
(ie, <2 y, >60 y) and with significant comorbidities and
underlying immunodeficiency.
Patients presenting with an impaired level of consciousness
are at increased risk for developing neurologic sequelae or
dying.
A seizure during an episode of meningitis also is a risk
factor for mortality or neurologic sequelae.
The presence of low-level pleocytosis (<20 cells) in patients
with bacterial meningitis suggests a poorer outcome.
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Delay in instituting effective antimicrobial therapy for
Acute bacterial meningitis result in increased morbidity and
mortality
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Meningitis caused by S pneumoniae, L monocytogenes, and
gram-negative bacilli has a higher case-fatality rate
compared to meningitis caused by other bacterial agents.
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Prognosis of meningitis caused by opportunistic pathogens
depends on the underlying immune function of the host.
Many of the survivors require lifelong suppressive therapy
(eg, long-term fluconazole for suppression in patients with
HIV-associated cryptococcal meningitis).