|
|
|
Overview |
|
|
Definition |
|
Meningitis is an inflammation of the meninges (the inner membranes of the
brain and spinal cord) that is most often caused by a viral or a bacterial
infection. Distinguishing between a viral and a bacterial infection is difficult
but essential because viral meningitis is usually benign and self-limited,
whereas untreated or improperly treated bacterial meningitis may result in brain
damage, learning disabilities, hearing loss, or even death. There are
approximately 25,000 cases of bacterial meningitis and 12,500 cases of viral
meningitis reported annually in the United States; of these, there are
approximately 2,200 deaths and 4,000 to 5,000 patients with significant
neurologic sequelae from bacterial infections. (Incidence rates vary in other
countries. In the United Kingdom, for example, there were an estimated 3,500
reported cases of meningococcal meningitis [meningococcal disease being the most
common cause of bacterial meningitis in children and young adults] in 1999.)
Other types of meningitis include, but are not limited to, fungal (e.g.
cryptococcus), tubercular, and chemical. |
|
|
Etiology |
|
Bacterial Meningitis
- Before 1986, meningitis was most often caused by Haemophilus
influenzae (45%), usually affecting infants and children under 6 years of
age. Since the introduction of a vaccine, H. influenzae meningitis has
virtually disappeared in the countries where the vaccine is administered.
- Neisseria meningitidis (meningococcal meningitis, 14% to 20%)
now causes most cases of meningitis in children and young adults; it is the only
type of meningitis that occurs in outbreaks.
- Streptococcus pneumonia (pneumococcal meningitis, 20%) is
frequently seen in patients with a recent history of upper respiratory
infection, pneumonia, otitis media, sinusitis, mastoiditis, or head injuries.
- Listeria monocytogenes (3% to 6%) meningitis often affects
neonates who have been infected by their mothers or elderly patients,
particularly those with preexisting medical conditions.
- Group B Streptococcus (S. agalactiae, 3% to 6%) often
affects neonates who have been infected by their mothers or by nursery
personnel, or adults over 60 years of age.
- Gram-negative bacilli (e.g., Escherichia coli, Proteus,
Pseudomonas aeruginosa, Klebsiella pneumoniae,
Salmonella spp., Enterococcus spp.) meningitis often affects head
trauma or neurosurgery patients.
- Staphylococcus aureus affects head trauma or neurosurgery
patients or patients with preexisting medical
conditions.
Viral Meningitis
- Common enteroviruses that cause meningitis (80% to 85%) include
echoviruses 3, 4, 5, 6, 7, 9, 11, 21, and 30 and coxsackieviruses A9,
B1, B2, B3, B4, and B5.
These viruses, which are most common among infants and small children, are
spread by the fecal-oral route, houseflies, wastewater, and sewage.
- Arboviruses are arthropod-transmitted and most often affect children.
The most common variety is St. Louis encephalitis virus.
- Mumps virus is a very common cause of meningitis in nonimmunized
individuals, usually children 5 to 9 years old.
- Lymphocytic choriomeningitis virus affects laboratory workers who have
contact with hamsters, rats, and mice or with their excreta.
- Of all the herpesviruses (e.g., herpes simplex virus types 1 (HSV-1)
and 2 (HSV-2), varicella-zoster virus, cytomegalovirus, Epstein-Barr virus,
herpesviruses 6 and 7), HSV-2 causes meningitis most often, especially following
the primary genital infection (36% of women; 19% of men).
- Human immunodeficiency virus (HIV) meningitis occurs as part of the
primary infection in 5% to 10% of
patients.
|
|
|
Risk Factors |
|
Bacterial Meningitis
- Crowded urban areas or dormitory living (meningococcal
disease)
- Otitis media, mastoiditis, sinusitis, pneumonia
- Significant head injury
- Cerebrospinal rhinorrhea
- Sickle-cell anemia (in children)
- Alcoholism
- Immunosuppression (pneumococcal disease)
- Neurosurgical procedures, skull trauma, endocarditis, and cancer
- Lack of H. influenza vaccine availability or
administration
Viral Meningitis
- Children who have not been immunized with the measles, mumps, rubella
(MMR) vaccine
- Persons who do not follow safe sex practices and are therefore at risk
for HSV-2 and HIV
- Laboratory workers who handle rats, hamsters, and mice or their
excreta
- Children who attend daycare centers
|
|
|
Signs and Symptoms |
|
- In neonates—irritability, high-pitched cry,
poor feeding, vomiting, fever (only 60%), stiff neck (only 15%), headache,
bulging fontanelle (only 30%), seizures
- In children and young adults—fever, headache,
vomiting, stiff neck, upper respiratory infection, photophobia, drowsiness,
Kernig's and Brudzinski's signs (50% of adults), petechiae or cutaneous
hemorrhages (50% of patients with N. meningitidis), and then confusion,
seizures (30%), obtundation, and loss of consciousness; N. meningitidis
can result in acute fulminating septicemia known as Waterhouse-Friedrichsen
syndrome, characterized by hypotensive shock from hemorrhage into the adrenal
glands
- In the elderly—an alteration in mental status
and lethargy may be the only signs of meningitis; often there is no fever and
signs of meningeal involvement are
variable.
|
|
|
Differential
Diagnosis |
|
- Subarachnoid hemorrhage
- Brain abscess
- Subdural empyema
- CNS neoplasm
- Various encephalopathies
- CNS syphilis
- Neurologic manifestations of Lyme disease
- Cerebral vasculitis
- Neuroleptic malignant syndrome
- Sarcoidosis
- Rocky Mountain spotted fever
- Multiple sclerosis
- Atypical migraine headache
|
|
|
Diagnosis |
|
|
Physical Examination |
|
Early diagnosis is the key to the successful treatment of meningitis. A
detailed history— including information about
pre-existing medical conditions; exposure to ticks, rodents, or birds;
alcoholism; and neurosurgical procedures—can help to
determine the most likely causative organism. When meningitis is suspected,
lumbar puncture is performed emergently so that a thorough examination of the
CSF can be done. Broad-spectrum antibiotic therapy is based on the physician's
initial clinical impression, age of the patient, and the patient's underlying
immunological status and is begun without waiting for culture
results. |
|
|
Laboratory Tests |
|
Bacterial Meningitis
- Lumbar puncture (LP)—to check opening
pressure (>180 mm H2O, up to 450 mm H2O) and assess
appearance of CSF (cloudy if >500 WBCs/mm3); WBCs (high; , between
100 and 100,000/mm3 with 80% PMNs); glucose (low; <1.9 mmol/L);
protein (high; >100 mg/dL); Gram stain of CSF (positive in 60% to 90% of
cases); CSF cultures are positive for the etiologic agent in 70% to 85% of
bacterial meningitis. (Caution: If papilledema or focal neurologic
symptoms are present, suggesting a mass lesion or mass effect, LP should be
deferred until obtaining a CT scan or MRI. However, antibiotic therapy should
not be delayed in the case of suspected bacterial meningitis even though this
may render the CSF sterile; the other findings will remain consistent with
bacterial meningitis.)
- Measurement of serum creatinine, electrolytes, blood urea
nitrogen—to determine renal function and electrolyte
balance
- Measurement of C-reactive protein concentration in the CSF (elevated
in 95% of patients)—a normal value excludes a
meningitis diagnosis
- DNA polymerase chain reaction (PCR) for H. influenza,
meningococci, streptococci, and Listeria
Viral Meningitis
- Blood cultures
- Lumbar puncture—CSF cell counts to detect
pleocytosis (cell count of 100 to 1,000/mm3) with lymphocyte
domination (although neutrophils may predominate in the first 48 hours; such a
finding should raise suspicion of bacterial meningitis); virus is infrequently
isolated from CSF; CSF protein will be slightly elevated; CSF glucose will be
slightly decreased; main purpose of this diagnostic test is to distinguish from
bacterial meningitis
|
|
|
Pathology/Pathophysiology |
|
Bacterial Meningitis
- Nasopharyngeal colonization, mucosal invasion, and then entry of
bacteria across the blood-brain barrier into the CSF where the host response is
usually ineffective
- Release of cytokines (e.g., tumor necrosis factor and interleukins 1
and 6) into the CSF, resulting in increased brain edema, increased intracranial
pressure and decreased cerebral blood flow, leading to cerebral
hypoxia
- Increased permeability of the blood-brain barrier, leading to
increased CSF protein levels
- Decreased glucose transport, leading to decreased glucose levels in
CSF
Viral Meningitis
- Entry of virus through the skin (e.g., mosquito vector) or
respiratory, gastrointestinal, or urogenital tracts
- Replication of the virus outside the CNS, then spread hematogenously
to CNS
- Cell count of 100 to 1,000/mm3 with neutrophils
predominating initially, then lymphocytes
- Mildly increased CSF protein and mildly decreased CSF
glucose
|
|
|
Imaging |
|
Computed tomography (CT) or MRI—in patients with
focal neurological findings to rule out an intracranial mass (e.g., cerebral
abscess, subdural empyema); imaging should not delay start of antibiotic
therapy. |
|
|
Other Diagnostic
Procedures |
|
- Counterimmunoelectrophoresis, latex agglutination test, enzyme-linked
immunosorbent assay, and coagglutination—to detect
antigens of meningeal microbes
- Polymerase chain reaction (PCR)—to illuminate
DNA from patients with meningitis from N. meningitidis and L.
monocytogenes; to detect enteroviral RNA and HSV DNA
- Echocardiogram, bone scan, or cultures of other body
fluids—to evaluate potential coexisting medical
conditions
|
|
|
Treatment Options |
|
|
Treatment Strategy |
|
When a patient presents acutely ill with the signs and symptoms of
meningitis, the following strategy may be warranted: (1) cultures should be
taken immediately to identify the offending organism, including from the blood
and CSF; (2) broad-spectrum antibiotics for presumed bacterial meningitis given
immediately (within the hour) prior to return of culture results.
Currently, there is no specific antiviral therapy available for infection
with enteroviruses, arboviruses, mumps virus, or lymphocytic choriomeningitis
virus; treatment is supportive only. HSV meningitis may be treated with
acyclovir, but it is not clear that the natural course of the disease is
changed. HIV meningitis is not treated with antiretroviral agents such as
zidovudine, didanosine, or dicalcitrine unless the CD4 lymphocyte count is below
500/mm3. Intravenous gamma-globulin is sometimes used as adjunctive
therapy for enteroviral meningitis. |
|
|
Drug Therapies |
|
The length of treatment varies with the organism being treated, ranging from
7 days for a meningococcal infection to 21 days for a Listeria infection.
- For neonates with likely pathogens of S. agalactiae, E.
coli, L. monocytogenes, and K.
pneumoniae—ampicillin plus third-generation
cephalosporins (e.g., cefotaxime, ceftriaxone) or ampicillin plus an
aminoglycoside such as gentamicin
- For infants with above pathogens plus S. pneumoniae, H.
influenzae, or
N. meningitidis—ampicillin (vancomycin
substituted if PCN allergic) plus a third-generation cephalosporin (e.g.,
cefotaxime, ceftriaxone)
- For children and young adults with S. pneumoniae, N.
meningitidis, or H. influenzae—a
third-generation cephalosporin plus vancomycin
- For adults with S. pneumoniae or L.
monocytogenes—ampicillin plus third-generation
cephalosporin (e.g., cefotaxime or ceftriaxone); third generation cephalosporin
plus vancomycin for penicillin-resistant strains (25%);
trimethoprim-sulfamethoxazole (TMP/SMX) and vancomycin for PCN
allergy
- For immunocompromised patients with S. pneumoniae, N.
meningitidis, L. monocytogenes, and P.
aeruginosa—vancomycin plus ampicillin plus
ceftazidime; TMP/SMX for penicillin-allergic patients
- For patients with recent head trauma or neurosurgery with likely
gram-positive and gram-negative organisms—vancomycin
plus ceftazidime
- Corticosteroid therapy (e.g., dexamethasone, 0.15 mg/kg every 6 hours
for 4 days, 2 to 3 hours before antimicrobial
therapy)—to reduce neurologic sequelae
- For seizures—diazepam (5 to 10 mg in adults)
and intravenous phenytoin
Dosages: ampicillin 2 g every 4 hours (children 50 mg/kg IV q 12 hours);
cefotaxime 2.0 gm IV every 4 to 6 hours; ceftazidime 2 g IV every 8 hours
(children 50 mg/kg IV q 12 hours); ceftriaxone 2 g every 12 hours (children 50
mg/kg IV QD); gentamicin 2 mg/kg IV load, then 1.7 mg/kg every 8 hours; TMP/SMX
160 mg/800 mg every 6 hours; vancomycin 1 g IV every 8 to 12 hours (children 15
mg/kg IV q 6 hours). |
|
|
Surgical Procedures |
|
- Surgical closure of CSF fistulas to prevent recurrent
meningitis
- Surgical correction of CSF
rhinorrhea
|
|
|
Complementary and Alternative
Therapies |
|
Bacterial meningitis has severe sequelae if not recognized and treated
aggressively. Nutritional and herbal therapies should be used only in support of
conventional treatment. Homeopathic remedies may be useful for symptomatic
relief and some herbal studies suggest efficacious antimicrobial and
immunomodulatory activities in the treatment of certain kinds of meningitis.
Garlic, for example, has demonstrated activity against cryptococcal meningitis
and appears to work synergistically with amphotericin B to treat this
condition.
To understand better how CAM therapies may be useful, some studies implicate
reactive oxygen species (ROS) and nitric oxide (NO) in the pathophysiologic
changes seen in early bacterial meningitis, particularly:
- Increased intracranial pressure
- Increased cerebral edema
- Increased CSF WBC count
The theory is that antioxidants would help to attenuate this damage. However,
results from studies of two antioxidants—vitamin C and
N-acetyl-L-cysteine—have been mixed and fairly
disappointing. |
|
|
Nutrition |
|
N-acetyl-L-cysteine (NAC)
N-acetyl-L-cysteine (NAC), an antioxidant, and S-methylisothiourea, an
inhibitor of inducible NO synthase (iNOS), have both been shown to limit early
pathological events in the course of bacterial meningitis. In view of these
results, an animal study was undertaken to evaluate the protective effects of
NAC and S-methylisothiourea against occurrences of advanced bacterial
meningitis. Treatment with NAC significantly reduced CSF white blood cell counts
but did not modulate CSF bacterial titers. In addition, although NAC did
modulate early brain changes in the rats with meningitis, the antioxidant did
not affect later brain manifestations of the disease. It is difficult to know
what to conclude from this information except, perhaps, that NAC may confer some
antioxidant properties against ROS early in the disease process, but does not
seem to impact upon the disease process during advanced stages in animals
(Koedel and Pfister 1997).
Vitamin C
Because vitamin C may be depleted in cases of infectious disease, it was
hypothesized that administering supplemental dosages of this vitamin might be
beneficial for patients with meningitis. However, in a controlled clinical trial
of this antioxidant, 42 children and infants hospitalized with acute meningeal
disease (either bacterial or viral) were randomly assigned to vitamin C or
placebo. The experimental group received an IV infusion of vitamin C, 100 mg/kg
up to a maximum of 3,000 mg infused over 30 minutes, followed by 50 mg/kg every
8 hours for a total of 9 doses over 3 days. Treatment failed to show any
beneficial effect on the clinical course of either form of meningitis compared
to placebo (Destro and Sharma 1977).
Vitamin B12
In a study of neurochemical markers in patients with aseptic and tuberculous
meningitis, decreased levels of vitamin B12 and significantly
increased levels of homocysteine were found only in CSF of patients with
tuberculous meningitis; no changes were noted in CSF of aseptic meningitis
patients (Qureshi et al. 1998). More research is needed to determine whether
measures to supplement vitamin B12 or decrease homocysteine can
influence the course of disease in patients with tuberculous meningitis.
Vitamin A
A study investigating meningococcal disease found that stores of vitamin A
were depleted in 41 children in sub-Saharan Africa; it is unknown whether
vitamin A supplementation would be beneficial for this condition (Semba et al.
1996). |
|
|
Herbs |
|
Garlic
In vitro experiments have demonstrated antifungal properties of garlic
(Allium sativum) as well as synergistic activities when garlic is
administered with amphotericin B. A concentrated garlic extract exhibited
fungistatic and fungicidal activities against three different isolates of C.
neoformans. On a weight basis, this concentrated extract of garlic was
determined to be as potent as fluconazole, ketoconazole, or 5-fluorocytosine but
was 60 times less potent than amphotericin B. Synergistic activity observed
between amphotericin B and the concentrated garlic extract was comparable to
that between amphotericin B and 5-fluorocytosine (Davis et al. 1994).
A small human case study of five patients with meningitis from
Cryptococcal neoformans suggests that the antifungal properties of garlic
seen in vitro may be conferred to people. In this study, commercial garlic
extract was administered to each of the five patients intravenously (1 mg/kg
body weight per day diluted into 500 ml saline over 4 hours) and no other
antimicrobial medications were given. Fungistatic activity was demonstrated in
three of the patients while fungicidal activity was demonstrated in the other
two (Davis et al. 1990).
More research is needed to fully evaluate both safety and efficacy of garlic
administration in the case of meningitis, as well as whether garlic has activity
against other kinds of meningitis; ideas for future study in this area are
intriguing.
Echinacea
Echinacea (Echinacea purpurea) has been shown to enhance nonspecific
immunity in immunosuppressed mice against systemic infections of L.
monocytogenes. In the immunosuppressed animals infected with L.
monocytogenes, echinacea extract reduced bacterial counts in the spleen
and liver to about 5% of the number in the untreated control animals and
significantly increased survival rates (Steinmuller et al. 1993). This study is
consistent with earlier results showing protection against a lethal dose of
L. monocytogenes in mice treated with polysaccharide extract of
echinacea soon after infection (Roesler et al. 1991).
Traditional Chinese Medicinal Herbs
Studies in Japan have used an animal model to demonstrate the efficacy of
traditional Chinese medicines in augmenting host resistance to L.
monocytogenes. Xiao-chai-hu-tang (Japanese name: Shosaiko-to) and
Ren-shen-yang-rong-tang (Japanese name: Ninjin-youei-to) were shown to enhance
macrophage-mediated protection (Yonekura et al. 1990; Yonekura et al. 1992). The
latter remedy contains:
- Angelicae archangelica (Angelica root)
- Atractylodis macrocephalae (Largehead atractylodis)
- Tuckahoe (Poria cocos)
- Rehmannia glutinosa (Rehmannia root)
- Panax ginseng (Asian ginseng)
- Cinnamomi aromaticum (Cinnamon bark)
- Citrus aurantium (Orange peel bitter)
- Paeoniae lactiflora (Peony root)
- Polygalae tenuifolia (Thinleaf Milkwort
root)
- Astragalus membranaceus (Milk vetch)
- Scisandrae chinensis (Chinese Magnoliavine fruit)
- Glycyrrhizae radix (Licorice root)
Shosaiko-to contains:
- Bupleurum falcatum L (Bupleurum)
- Pinellia ternata (Pinelliae tuber)
- Scutellariae baicalensis (Skullcap root)
- Zizyphi jujube (Jujube)
- Panax ginseng (Asian ginseng)
- Glycyrrhizae radix (Licorice root)
- Zingiber officinale (Ginger
root)
Traditionally, these remedies have been used in combination. Direction of
treatment, using herbal therapies as adjuncts to other medical care, is best
directed by a trained, licensed, and certified specialist. |
|
|
Homeopathy |
|
Clinical trials evaluating the safety or efficacy of homeopathy for
meningitis have not been documented to date; there are certain remedies, though,
used in clinical practice as adjuncts to treat meningitis that are reportedly
beneficial in helping to alleviate symptoms. Remedies include Apis, Arnica,
Bryonia, Helleborus, and Hyoscyamus (Morrison 1993).
- Apis—for meningitis in children with
intense head pain that drives them to bore their head into the pillow. Infants
for whom this treatment is appropriate may have a bulging fontanelle.
- Arnica—for meningitis following
surgery or head trauma. The appropriate patient will often insist that there is
nothing wrong.
- Bryonia—for meningitis with delirium
and a characteristic movement of the mouth in which the jaw moves side to side
quite rapidly in a somewhat contorted manner.
- Helleborus—for meningitis with
stupefaction and apathy, although patients may also be anguished and pleading
for help. Delirium and shaking or rolling of the head may be present.
- Hyoscyamus—for meningitis with
convulsions that occur with shrieking and grinding of the
teeth.
|
|
|
Patient Monitoring |
|
Patients must be monitored in the intensive care unit for 24 to 48 hours for
the following reasons: to be sure that the antimicrobial agent is having an
effect; to observe for seizure activity; and to prevent aspiration. CSF
examination should be repeated after 24 to 48 hours if there is no clinical
improvement. |
|
|
Other
Considerations |
|
|
Prevention |
|
- For chemoprophylaxis—rifampin (600 mg,
adults; 5 mg/kg, children every 12 hours for 4 doses) is given to household
contacts to eradicate nasopharyngeal colonization of meningococcal
infection
- Meningococcal vaccine (groups A, C, Y,
W135)—to immunize during epidemics and for persons
traveling to endemic areas
- H. influenzae type B (HIB) vaccine—for
pediatric population
- Pneumococcal vaccine—to prevent pneumonia in
elderly and debilitated patients; not effective in children under 2 years of
age; given post-splenectomy as well
- Live, attenuated mumps vaccine—for pediatric
population
|
|
|
Complications/Sequelae |
|
- Sensorineural hearing loss (10% of children)
- Seizures (20% to 30% of patients), which may be reversible
- Cerebral edema (25% of fatal cases)
- Hemiparesis, dysphasia, visual field defects, gaze disturbances (25%
of adults)
- Intellectual deficits, ataxia, and blindness
- Loss of airway reflexes, vasomotor collapse, and respiratory
arrest
- Recurrent meningitis (most common in patients with head trauma) is
most often due to S. pneumoniae but occasionally to H.
influenzae.
- Vancomycin is contraindicated as a single agent because of its erratic
CSF penetration; CSF levels of vancomycin may be reduced by
dexamethasone.
- Imipenem and meropenem are effective against pneumococcal meningitis
but have epileptogenic activity.
- Corticosteroids should not be used when patients present with severe
sepsis or septic shock.
|
|
|
Prognosis |
|
Although there are many new antimicrobial agents used for bacterial
meningitis, the morbidity and mortality are still unacceptably high.
Approximately 25% of adults who contract bacterial meningitis will die, and 60%
of infants who survive the infection will have neurologic sequelae or
developmental difficulties. Most patients recover completely from viral
meningitis without sequelae. |
|
|
Pregnancy |
|
Pregnant women often carry L. monocytogenes and S. agalactiae
asymptomatically in their genital tract or rectum and transmit these infections
to their children during birth. Pregnant women should not take rifampin for
prophylaxis as risks to the fetus have not been
determined. |
|
|
References |
|
Andes DR, Craig WA. Pharmacokinetics and pharmacodynamics of antibiotics in
meningitis. Infect Dis Clin North Am. 1999;13(3):595-618.
Ashwal S, Perkin RM, Thompson JR, Schneider S, Tomasi LG. Bacterial
meningitis in children: current concepts of neurologic management. Curr Prob
Pediatr. 1994;24(8)267-284.
Ashwal S, Tomasi L, Schneider S, Perkin R, Thompson J. Bacterial meningitis
in children: pathophysiology and treatment. Neurology.
1992;42(4):739-748.
Coyle PK. Overview of acute and chronic meningitis. Neurol Clin.
1999;17(4):691-710.
Davis LE, Shen J, Royer RE. In vitro synergism of concentrated
Allium sativum extract and amphotericin B against Cryptococcus
neoformans. Planta Med. 1994;60(6):546-549.
Davis LE, Shen JK, Cai Y. Antifungal activity in human cerebrospinal fluid
and plasma after intravenous administration of Allium sativum.
Antimicrob Agents Chemother. 1990:34(4)651-653.
de Louvois J. Acute bacterial meningitis in the newborn. J Antimicrob
Chemother. 1994;34:(Suppl A):61-73.
Destro RL, Sharma V. An appraisal of vitamin C in adjunct therapy of
bacterial and "viral" meningitis. Clin Pediatr. 1977;16(10):936-939.
Gold R. Epidemiology of bacterial meningitis. Infect Dis Clin North
Am. 1999;13(3): 515-525.
Hart CA, Cuevas Le, Marzouk O, Thomson AP, Sills J. Management of bacterial
meningitis. J Antimicrob Chemother. 1993;32:(Suppl A):49-59.
Hasbun R, Aronin SI, Quagliarello VJ. Treatment of bacterial meningitis.
Compr Ther. 1999;25(2):73-81.
Kaplan SL. Clinical presentations, diagnosis, and prognostic factors of
bacterial meningitis. Infect Dis Clin North Am. 1999;13(3):579-594.
Klugman KP, Madhi SA. Emergence of drug resistance. Impact on bacterial
meningitis. Infect Dis Clin North Am. 1999;13(3):637-646.
Koedel U, Pfister HW. Protective effect of the antioxidant
N-acetyl-L-cysteine in pneumococcal meningitis in the rat. Neurosci Lett.
1997;225(1):33-36.
Kornelisse RF, de Groot R, Neijens HJ. Bacterial meningitis: mechanisms of
disease and therapy. Eur J Pediatr. 1995;154(2):85-96.
Lauritsen A, Oberg B. Adjunctive corticosteroid therapy in bacterial
meningitis. Scand J Infect Dis 1995;27(5):431-434.
LeFrock JL. Acute bacterial meningitis. In: Conn RB, Borer WZ, Snyder JW,
eds. Current Diagnosis 9. Philadelphia, Pa: W.B. Saunders Company;
1997:821-825.
Meningitis Research Foundation. About Meningitis and Septicaemia. Accessed at
www.meningitis.org/whatis.html on October 20, 2000.
Miller LG, Choi C. Meningitis in older patients: how to diagnose and treat a
deadly infection. Geriatrics. 1997;52(8):43-44, 47-50, 55.
Morrison R. Desktop Guide to Keynotes and Confirmatory Symptoms.
Albany, Calif: Hahnemann Clinic Publishing; 1993:27-30, 36-39, 72-75, 176-177,
184-186.
Peltola H. Prophylaxis of bacterial meningitis. Infect Dis Clin North
Am. 1999;13(3):685-710.
Pfister HW, Scheld WM. Brain injury in bacterial meningitis: therapeutic
implications. Curr Opin Neurol. 1997;10(3):254-259.
Pong A, Bradley JS. Bacterial meningitis and the newborn infant. Infect
Dis Clin North Am. 1999;13(3):711-733.
Quagliarello VJ, Scheld WM. Treatment of bacterial meningitis. N Engl J
Med. 1997;336(10):708-716.
Qureshi GA, Baig SM, Bednar I, Halawa A, Parvez SH. The neurochemical markers
in cerebrospinal fluid to differentiate between aseptic and tuberculous
meningitis. Neurochem Int. 1998;32(2):197-203.
Radetsky M. Duration of symptoms and outcome in bacterial meningitis: an
analysis of causation and the implications of a delay in diagnosis. Pediatr
Infect Dis J. 1992;11(9):694-698.
Rockowitz J, Tunkel AR. Bacterial meningitis. Practical guidelines for
management. Drugs. 1995;50(5):838-853.
Roesler J, Steinmuller C, Kiderlen A, Emmendorffer A, Wagner H,
Lohmann-Matthes ML. Application of purified polysaccharides from cell cultures
of the plant Echinacea purpurea to mice mediates protection
against systemic infections with Listeria monocytogenes and Candida
albicans. Int J Immunopharmacol. 1991;13(1):27-37.
Rosen P, et al. Emergency Medicine: Concepts and Clinical Practice.
Vol 3. 4th ed. St. Louis, Mo: Mosby; 1998:2198-2209.
Saez-Llorens X, McCracken GH Jr. Antimicrobial and anti-inflammatory
treatment of bacterial meningitis. Infect Dis Clin North Am.
1999;13(3):619-636.
Schaad UB, Kaplan SL, McCracken GH Jr. Steroid therapy for bacterial
meningitis. Clin Infect Dis. 1995;20(3):685-690.
Scheld WM. Bacterial meningitis. In: Conn RB, et al, eds. Conn's Current
Therapy. Philadelphia, Pa: W.B. Saunders Company; 1999:102-108.
Segreti J, Harris AA. Acute bacterial meningitis. Infect Dis Clin North
Am. 1996;10(4):797-809.
Semba RD, Bulterys M, Munyeshuli V, et al. Vitamin A deficiency and T-cell
subpopulations in children with meningococcal disease. J Trop Pediatr.
1996;42(5):287-290.
Sormunen P, Kallio MJ, Kilpi T, Peltola H. C-reactive protein is useful in
distinguishing Gram stain-negative bacterial meningitis from viral meningitis in
children. J Pediatr. 1999;134(6):725-729.
Spach DH, Jackson LA. Bacterial meningitis. Neurol Clin.
1999;17(4):711-735.
Steinmuller C, Roesler J, Grottrup E, Franke G, Wagner H, Lohmann-Matthes ML.
Polysaccharides isolated from plant cell cultures of
Echinacea purpurea enhance the resistance of immunosuppressed mice
against systemic infections with Candida albicans and Listeria
monocytogenes. Int J Immunopharmacol. 1993;15(5):605-614.
Swartz MN. Bacterial meningitis. In: Cecil Textbook of Internal
Medicine. Vol 2. 21st ed. Philadelphia, Pa: W.B. Saunders Company;
2000:1645-1654.
Tunkel AR, Scheld WM. Acute meningitis. In: Mandell GL, et al, eds.
Mandell, Douglas, and Bennett's Principles of Infectious Diseases. 4th
ed. New York, NY: Churchill Livingstone; 1995:831-858.
Tunkel AR, Scheld WM. Issues in the management of bacterial meningitis. Am
Fam Physician. 1997;56(5):1355-1362.
Yonekura K, Kawakita T, Mitsuyama M, et al. Induction of colony-stimulating
factor(s) after administration of a traditional Chinese medicine,
Xiao-chai-hu-tang (Japanese name: Shosaiko-to). Immunopharmacol
Immunotoxicol. 1990;12(4):647-667.
Yonekura K, Kawakita T, Saito Y, Suzuki A, Nomoto K. Augmentation of host
resistance to Listeria monocytogenes infection by a traditional Chinese
medicine, Ren-shen-yang-rong-tang (Japanese name: Ninjin-youei-to).
Immunopharmacol Immunotoxicol.
1992;14(1-2):165-190. |
|
Copyright © 2000 Integrative Medicine
Communications This publication contains
information relating to general principles
of medical care that should not in any event be construed as specific
instructions for individual patients. The publisher does not accept any
responsibility for the accuracy of the information or the consequences arising
from the application, use, or misuse of any of the information contained herein,
including any injury and/or damage to any person or property as a matter of
product liability, negligence, or otherwise. No warranty, expressed or implied,
is made in regard to the contents of this material. No claims or endorsements
are made for any drugs or compounds currently marketed or in investigative use.
The reader is advised to check product information (including package inserts)
for changes and new information regarding dosage, precautions, warnings,
interactions, and contraindications before administering any drug, herb, or
supplement discussed herein. | |