TREATMENT

TREATMENT
Therapeutic approach to px w/ presumed bacterial
meningitis depends on the nature of the initial
manifestations of the illness.
A child w/ rapidly progressing dse of <24 hr duration,
in the absence of increased ICP, should receive
antibiotics ASAP after an LP is performed.
If there are signs of increased ICP or focal neurologic
findings, antibiotics should be given w/out performing
an LP & before obtaining a CT scan.
Increased ICP should be treated simultaneously
Immediate tx of MOSF, shock, & ARDS is also
indicated.
 Px who have a more protracted subacute course &
become ill over a 47 day period should also be
evaluated for signs of increased ICP & focal neurologic
deficits.
Unilateral headache, papilledema, & other signs of
increased ICP suggest a focal lesion such as a brain or
epidural abscess, or subdural empyema.
Under these circumstances, antibiotic therapy
should be initiated before LP and CT scanning.
If no signs of increased ICP are evident, an LP should
be performed.
Initial Antibiotic Therapy
The initial (empirical) choice of therapy for
meningitis in immunocompetent infants and
children is primarily influenced by the
antibiotic susceptibilities of S. pneumoniae.
Selected antibiotics should achieve
bactericidal levels in the CSF.
Although there are substantial geographic
differences in the frequency of resistance of S.
pneumoniae to antibiotics, rates are
increasing throughout the world.
2550% of strains of S. pneumoniae are currently
resistant to penicillin
Resistance to cefotaxime & ceftriaxone is also evident
in up to 25% of isolates.
In contrast, most strains of N. meningitidis are
sensitive to penicillin and cephalosporins, although
rare resistant isolates have been reported.
Approximately 3040% of isolates of H. influenzae b
produce - lactamases and, therefore, are resistant to
ampicillin.
These -lactamase-producing strains are sensitive to
the extended-spectrum cephalosporins.
Based on the substantial rate of resistance of S. pneumoniae
to -lactam drugs, vancomycin (60 mg/kg/24 hr, given every 6
hr) is recommended as part of initial empirical therapy.
Because of the efficacy of 3rd-generation cephalosporins in
the therapy of meningitis caused by sensitive S. pneumoniae,
N. meningitidis, and H. influenzae type b, cefotaxime (200
mg/kg/24 hr, given every 6 hr) or ceftriaxone (100 mg/kg/24
hr administered once per day or 50 mg/kg/dose, given every
12 hr) should also be used in initial empirical therapy.
Patients allergic to -lactam antibiotics & >1 mo of age can be
treated with chloramphenicol, 100 mg/kg/24 hr, given every 6
hr.
Alternately, patients can be desensitized to the antibiotic
DURATION OF ANTIBIOTIC THERAPY
Therapy for uncomplicated penicillin-sensitive S.
pneumoniae meningitis should be completed with 10
to 14 days with a 3rd-generation cephalosporin or IV
penicillin (400,000 U/kg/24 hr, given every 46 hr).
If the isolate is resistant to penicillin and the 3rd-
generation cephalosporin, therapy should be
completed w/ vancomycin.
IV penicillin (400,000 U/kg/24 hr) for 57 days is the tx
of choice for uncomplicated N. meningitidis meningitis.
Uncomplicated H. influenzae type b meningitis should
be treated for 710 days.
Pxwho receive IV or oral antibiotics before LP
& who do not have an identifiable pathogen
but do have evidence of an acute bacterial
infection on the basis of their CSF profile
should continue to receive therapy w/
ceftriaxone or cefotaxime for 710 days.
If focal signs are present or the child does not
respond to tx, a parameningeal focus may be
present & a CT or MRI scan should be
performed.
 A routine repeat LP is not indicated in px w/
uncomplicated meningitis due to antibiotic-sensitive S.
pneumoniae, N. meningitidis, or H. influenzae type b.
Repeat examination of CSF is indicated in some
neonates, in px w/ g(-) bacillary meningitis, or in
infection caused by a -lactam-resistant S.
pneumoniae.
The CSF should be sterile w/in 2448 hr of initiation of
appropriate antibiotic therapy.
 Meningitis due to E. coli or P. aeruginosa requires
therapy w/ a 3rd-generation cephalosporin active
against the isolate in vitro.
Most isolates of E. coli are sensitive to cefotaxime or
ceftriaxone, & most isolates of P. aeruginosa are
sensitive to ceftazidime.
G(-) bacillary meningitis should be treated for 3 wk or
for at least 2 wk after CSF sterilization, w/c may occur
after 210 days of tx.
 Side effects of antibiotic therapy of meningitis include
phlebitis, drug fever, rash, emesis, oral candidiasis,
and diarrhea.
Ceftriaxone may cause reversible gallbladder
pseudolithiasis, detectable by abdominal
ultrasonography.
This is usually asymptomatic but may be associated
with emesis and upper right quadrant pain.
Corticosteroids
Rapid killing of bacteria in the CSF effectively sterilizes
the meningeal infection but releases toxic cell products
after cell lysis (cell wall endotoxin) that precipitates the
cytokine-mediated inflammatory cascade.
The resultant edema formation & neutrophilic
infiltration may produce additional neurologic injury w/
worsening of CNS signs & symptoms.
Therefore, agents that limit production of inflammatory
mediators may be of benefit to px w/ bacterial
meningitis.
 Data support the use of IV dexamethasone, 0.15
mg/kg/dose given every 6 hr for 2 days, in the tx of
children older than 6 wk w/ acute bacterial meningitis
caused by H. influenzae type b.
Among children w/ meningitis due to H. influenzae type b,
corticosteroid recipients have a shorter duration of fever,
lower CSF protein & lactate levels, & a reduction in SNHL
Data in children regarding the benefit, if any, of
corticosteroids in the tx of meningitis caused by other
bacteria are inconclusive.
Early tx of adults w/ bacterial meningitis, especially those
w/ pneumococcal meningitis, however, results in improved
outcome.
 Corticosteroids appear to have max. benefit if given 1
2 hr before antibiotics are initiated.
They also may be effective if given concurrently w/ or
soon after the 1st dose of antibiotics.
Complications of corticosteroids include
GI bleeding, HPN, hyperglycemia, leukocytosis, &
rebound fever after the last dose.
Supportive Care
Repeated medical & neurologic assessments of px w/
bacterial meningitis are essential to identify early signs
of cardiovascular, CNS, & metabolic complications.
Pulse rate, BP, & RR should be monitored frequently.
Neurologic assessment, including pupillary reflexes,
level of consciousness, motor strength, cranial nerve
signs, and evaluation for seizures, should be made
frequently in the 1st 72 hr, when the risk of neurologic
complications is greatest.
 Important laboratory studies include an assessment of
BUN;
serum sodium, chloride, potassium, and bicarbonate
levels;
urine output and specific gravity;
complete blood and platelet counts;
and, in the presence of petechiae, purpura, or
abnormal bleeding, measure of coagulation function
(fibrinogen, prothrombin, and partial thromboplastin
times).
 Pxshould initially receive nothing by mouth.
If a px is judged to be normovolemic, w/ normal BP, IV
fluid administration should be restricted to one half to
two thirds of maintenance, or 8001,000 mL/m2/24 hr,
until it can be established that increased ICP or SIADH
is not present.
Fluid administration may be returned to normal (1,500
1,700 mL/m2/24 hr) when serum Na levels are normal.
Fluid restriction is not appropriate in the presence of
systemic hypotension because reduced blood pressure
may result in reduced cerebral perfusion pressure &
CNS ischemia.
 Shock must be treated aggressively to prevent brain &
other organ dysfunction (ATN, ARDS).
Px w/ shock, a markedly elevated ICP, coma, and
refractory seizures require intensive monitoring w/
central arterial & venous access & frequent vital signs,
necessitating admission to a pediatric ICU.
Px w/ septic shock may require fluid resuscitation &
therapy w/ vasoactive agents such as dopamine &
epinephrine
The goal of such therapy in px w/ meningitis is to avoid
excessive increases in ICP w/out compromising blood
flow & oxygen delivery to vital organs.
 Neurologic complications include increased ICP w/
subsequent herniation, seizures, & an enlarging head
circumference due to a subdural effusion or
hydrocephalus.
Signs of increased ICP should be treated emergently w/
endotracheal intubation & hyperventilation (to
maintain the pCO2at 25 mm Hg).
 In addition, intravenous furosemide (Lasix, 1 mg/kg) &
mannitol (0.51.0 g/kg) osmotherapy may reduce ICP
Furosemide reduces brain swelling by venodilation
and diuresis without increasing intracranial blood
volume
Mannitol produces an osmolar gradient between the
brain & plasma, thus shifting fluid from the CNS to
the plasma, w/ subsequent excretion during an
osmotic diuresis.
Seizures are common during the course of bacterial
meningitis.
Immediate therapy for seizures includes IV diazepam (0.10.2
mg/kg/dose) or lorazepam (0.050.10 mg/kg/dose), and
careful attention paid to the risk of respiratory suppression.
Serum glucose, calcium, and sodium levels should be monitored.
After immediate management of seizures, px should receive
phenytoin (1520 mg/kg loading dose, 5 mg/kg/24 hr
maintenance) to reduce the likelihood of recurrence.
Phenytoin is preferred to phenobarbital because it produces less
CNS depression & permits assessment of a patient's level of
consciousness.
Serum phenytoin levels should be monitored to maintain them in
the therapeutic range (1020 g/mL).
COMPLICATIONS
During the treatment of meningitis, acute CNS
complications can include
seizures, increased ICP, cranial nerve palsies, stroke,
cerebral or cerebellar herniation, and thrombosis of
the dural venous sinuses.
Collections of fluid in the subdural space develop in 1030%
of px w/ meningitis & are asymptomatic in 8590% of px.
Subdural effusions are especially common in infants.
Symptomatic subdural effusions may result in a bulging
fontanel, diastasis of sutures, enlarging head circumference,
emesis, seizures, fever, and abnormal results of cranial
transillumination.
CT or MRI scanning confirms the presence of a subdural
effusion.
In the presence of increased ICP or a depressed level of
consciousness, symptomatic subdural effusion should be
treated by aspiration through the open fontanel
Fever alone is not an indication for aspiration.
 SIADH occurs in some patients with meningitis,
resulting in hyponatremia and reduced serum
osmolality.
This may exacerbate cerebral edema or result in
hyponatremic seizures
 Fever associated w/ bacterial meningitis usually
resolves w/in 57 days of the onset of therapy.
Prolonged fever (>10 days) is noted in about 10% of
px.
Prolonged fever is usually due to intercurrent viral
infection, nosocomial or secondary bacterial infection,
thrombophlebitis, or drug reaction.
Secondary fever refers to the recrudescence of
elevated temperature after an afebrile interval.
 Nosocomial infections are especially important to
consider in the evaluation of these px.
Pericarditis or arthritis may occur in px being treated
for meningitis, especially that caused by N.
meningitidis.
Involvement of these sites may result either from
bacterial dissemination or from immune complex
deposition.
In general, infectious pericarditis or arthritis occurs
earlier in the course of tx than does immune-mediated
disease.
 Thrombocytosis, eosinophilia, & anemia may develop
during therapy for meningitis.
Anemia may be due to hemolysis or BM suppression.
DIC is most often associated w/ the rapidly progressive
pattern of presentation & is noted most commonly in
px w/ shock & purpura.
The combination of endotoxemia & severe hypotension
initiates the coagulation cascade;
the coexistence of ongoing thrombosis may produce
symmetric peripheral gangrene.
PROGNOSIS
Appropriate antibiotic therapy & supportive care have
reduced the mortality of bacterial meningitis after the
neonatal period to <10%.
The highest mortality rates are observed w/
pneumococcal meningitis.
Severe neurodevelopmental sequelae may occur in
1020% of px recovering from bacterial meningitis, &
as many as 50% have some, albeit subtle,
neurobehavioral morbidity.
 The prognosis is poorest among infants younger than 6
mo & in those w/ high concentrations of
bacteria/bacterial products in their CSF.
Those w/ seizures occurring more than 4 days into
therapy or w/ coma or focal neurologic signs on
presentation have an increased risk of long-term
sequelae.
There does not appear to be a correlation between
duration of symptoms before diagnosis of meningitis &
outcome.
 The most common neurologic sequelae include hearing
loss, mental retardation, recurrent seizures, delay in
acquisition of language, visual impairment, and
behavioral problems.
Sensorineural hearing loss is the most common sequela
of bacterial meningitis &, usually, is already present at
the time of initial presentation.
It is due to labyrinthitis after cochlear infection and occurs
in as many as 30% of px w/ pneumococcal meningitis,
10% with meningococcal, and 520% of those with H.
influenzae type b meningitis.
Hearing loss may also be due to direct inflammation of the
auditory nerve.
 All px w/ bacterial meningitis should undergo careful
audiologic assessment before or soon after discharge
from the hospital.
Frequent reassessment on an outpatient basis is
indicated for patients who have a hearing deficit.