Bacterial Meningitis
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Dr. Sudheer Kher
Case Study<br />
• A 3 yr old girl was brought to the emergency room by<br />
her parents because of fever and loss of appetite for the<br />
past 24 hrs and difficulty in arousing her for the past 2<br />
hrs.<br />
• The developmental history had been normal since birth.<br />
Her childhood immunization were current.<br />
• She attended a day care center and had a history of<br />
several episodes of presumed viral infections similar to<br />
those of other children at the center.
Clinical Features<br />
• Temperature was 39.5 C<br />
• Pulse-130/min<br />
• Respirations-24/min<br />
• BP-110/60 mm Hg
Physical Examination<br />
• Physical examination showed a well-developed and well-nourished<br />
child of normal height and weight who was drowsy.<br />
• When her neck was passively flexed, her legs also flexed (+ve<br />
Brudzinski sign, suggesting irritation of meninges).<br />
• Ophthalmoscopic examination showed no papilledema, indicating<br />
that there had been no long-term increase in intracranial pressure.<br />
• The remainder of her physical examination was normal.
Laboratory Findings<br />
• CSF fluid was cloudy. Gram staining showed many<br />
polymorphonuclear cells with gram negative diplococci<br />
suggestive of neisseria meningitidis.<br />
• White blood cell count – 25,000/µL ( markedly elevated), with<br />
88% PMN forms and an absolute PMN count of 22,000/µL<br />
(markedly elevated), 6% lymphocytes, and 6% monocytes.<br />
• CSF protein was 100 mg/dL (elevated)<br />
• Glucose was 15 mg/dL (low, termed hypoglycorrhachia)<br />
• Cultures of blood and CSF grew serogroup B N.<br />
MENINGITIDIS
What is meningitis<br />
• <strong>Meningitis</strong> is a common name for infections (inflammation)<br />
that take place in the meninges surrounding the brain and<br />
spinal cord.<br />
• One of the most serious forms of meningitis is<br />
Meningococcal meningitis. It is caused by Neisseria<br />
meningitidis.<br />
• An infection with meningococcal bacteria causes a serious,<br />
potentially fatal infection called meningococcal disease. You<br />
may have heard it referred to as bacterial meningitis.<br />
Meningococcal disease can also cause a very serious condition<br />
called sepsis (blood poisoning).
Types of meningitis<br />
• Aseptic meningitis: caused by viruses (e.g. mumps), SLE, and<br />
some types of medications.<br />
• <strong>Bacterial</strong> meningitis: caused by a bacterial infection.<br />
Numerous microorganisms may cause bacterial meningitis:<br />
• Neiseria meningitidis<br />
• Streptococcus pneumoniae<br />
• Listeria monocytogenes<br />
• Haemophilus influenzae (type B)<br />
• Mycobacterium tuberculosis<br />
• Group B Streptococci<br />
• Escherichia coli
Types of meningitis (cont.)<br />
• Viral meningitis: caused by viruses (enterovirus).<br />
• Tuberculous meningitis: caused by tuberculosis infection<br />
due to Mycobacterium tuberculosis.<br />
• Cryptococcal meningitis: caused by infection from a yeast<br />
called Cryptococcus (found in soil and bird droppings). Often<br />
associated with AIDS.<br />
• Neoplastic meningitis: caused by the spread of solid<br />
tumors to the brain or spinal cord.<br />
• Syphilitic meningitis: due to infection with the bacterium<br />
that causes syphilis
Epidemiology<br />
• SOURCE & RESERVOIR:<br />
• Man<br />
• Subclinical infection<br />
• carrier (they carry the bacteria in their nose and throat but<br />
never become sick)<br />
• MODES OF TRANSMISSION:<br />
• Close contact with a person who is sick with the disease<br />
• Contact with carriers<br />
• Living in close quarters, such as college dormitories<br />
• Being in crowded situations for prolonged periods of time<br />
• Sharing drinking glasses, water bottles, or eating utensils<br />
• Kissing, sharing a cigarette
Epidemiology (cont.)<br />
• INFECTIOUS MATERIAL:<br />
• Nasopharyngeal secretions<br />
• PEOPLE AT RISK:<br />
• Neonates<br />
• Children, teens, and young adults<br />
• Elderly<br />
• People who have a weakened immune system<br />
• AIDS patients are at high risk for Tuberculous meningitis
Etiology<br />
• <strong>Bacterial</strong> meningitis is due most often to hematogenous spread<br />
of bacteria to the leptomeninges.<br />
• It can also be seen after head trauma as skull fracture through<br />
the sinuses.<br />
• Local infections such as mastoiditis may also lead to meningitis.<br />
• Surgery or CNS infection such as cranial epidural abscess may<br />
lead to meningitis.
Etiology (cont.)<br />
• Neonates: Group B Streptococci, Escheridia coli, Listeria<br />
monocytogenes<br />
• Infants: Neissera meningitidis, Haemophilus influenzae,<br />
Streptococcus pneumoniae<br />
• Children: N. meningitidis, S. pneumoniae<br />
• Adults: S. pneumoniae, N. meningitidis, Mycobacteria,<br />
Cryptococci
Pathogenesis<br />
• Bacteria extend through the wall of blood vessels into the<br />
subarachnoid space followed more slowly by neutrophils as<br />
the blood brain barrier breaks down.<br />
• The combination of bacteria and neutrophils in the<br />
subarachnoid space irritates the underlying cerebral cortex<br />
causing edema and increased intracranial pressure.<br />
• If the meningitis is not treated neutrophils are followed by<br />
lymphocytes and macrophages which with the bacteria, cause<br />
irritation and degeneration of cranial nerves, production of<br />
intimal fibrosis in arteries and fibrosis of the leptomeninges<br />
which can lead to cortical infarcts and blockage of the<br />
foramina of Lushcka and Magendie with hydrocephalus.
Pathogenesis
General Gross Description<br />
• The brain in purulent meningitis has an opacity of the<br />
leptomeninges by neutophils and bacteria. This is seen<br />
over the convexity and the base.<br />
• The brain is also usually swollen.
General Microscopic<br />
Description<br />
• In acute purulent meningitis, the subarachnoid space is filled<br />
with neutrophils and bacteria with increasing numbers of<br />
macrophages and lymphocytes over time.<br />
• The underlying brain is usually protected by the pia so that<br />
there is no intracerebral inflammation, however, the cortex<br />
and white matter will show spongy change or vacuolization<br />
due to edema.<br />
• Infants more often show bacteria and neutrophils invading the<br />
underlying parenchyma.
Symptoms<br />
• Sudden high fever :<br />
The infection causes a high fever of about 130F or more which does<br />
not get lower with a tepid bath or fever reducing medicine<br />
• Severe, persistent headache<br />
• Neck stiffness and pain that makes it difficult to touch your chin to<br />
your chest is due to the swelling around the Meninges<br />
• Nausea and vomiting, sometimes along with diarrhea<br />
• Confusion and disorientation (acting "goofy") can progress to stupor,<br />
coma, and death<br />
• Drowsiness or sluggishness<br />
• Eye pain or sensitivity to bright light<br />
• Muscle or joint pain or weakness
Symptoms<br />
• Abnormal skin color<br />
• Reddish or brownish skin rash or purple spots that do not turn<br />
white when u press on them are a sign of sepsis. These may develop<br />
because of inflammation and bleeding in small blood vessels<br />
throughout the body, including those under the skin.<br />
• Ice-cold hands and feet<br />
• Numbness and tingling: Sepsis (also called blood poisoning) can<br />
reduce the amount of blood that gets to the persons hand and feet,<br />
causing coldness and numbness.<br />
• Seizures: Swelling of brain tissue, increases pressure inside the skull,<br />
and hampers blood flow, causing stroke symptoms, paralysis and<br />
seizures.
Glass Test<br />
• Press the side of the glass<br />
tumbler against the rash<br />
• If the rash does not disappear<br />
then it is a symptom of<br />
meningitis.
Symptoms In Children<br />
• Severe high fever<br />
• Feeding problems<br />
• Vomiting<br />
• Irritability<br />
• Seizures<br />
• High-pitched crying<br />
• Decreased appetite<br />
• The skin over the fontanelles (soft spots between the<br />
skull bones) becomes taut, and the fontanelles may bulge.<br />
• Infants may not develop a stiff neck
Diagnosis<br />
WHEN TO CALL THE DOCTOR:<br />
• If a child 2 years old or younger has an unexplained fever and<br />
the parent senses that the child is ill.<br />
• If a child becomes increasingly irritable or unusually sleepy,<br />
refuses to eat, vomits, has seizures, or develops a stiff neck.<br />
• If an adult has fever, headache, skin rash, confusion,<br />
unresponsiveness (stupor), seizures, and a stiff neck.
Diagnosis (cont.)<br />
KERNIG SIGN:<br />
• The Kernig sign is positive if pain in the lower back or<br />
posterior thigh occurs when the knee is extended while the<br />
patient is lying in the supine position and the hip is flexed at a<br />
right angle.
Diagnosis (cont.)<br />
BRUDZINSKI SIGN:<br />
• The Brudzinski sign is positive if knee and hip flexion occurs<br />
when the neck is flexed while the patient is in the supine<br />
position.
Diagnosis (cont.)<br />
NECK STIFFNESS:<br />
• Nuchal rigidity is typically assessed with the patient lying<br />
supine, and both hips and knees flexed.<br />
INVESTIGATIONS DONE:<br />
• Blood test<br />
• Chest X-ray<br />
• CSF analysis<br />
• CT scan or MRI (MRI preferred over CT due to its<br />
superiority in demonstrating areas of cerebral edema, ischemia,<br />
and meningeal inflammation)<br />
• Cultures of samples of CSF, blood, urine, mucus from the nose<br />
and throat, and pus from skin infections.
Diagnosis – CT Scan
Diagnosis (cont.)<br />
CSF ANALYSIS:<br />
• A spinal tap (lumbar puncture) is performed. A thin needle is<br />
inserted between L4/L5 to withdraw a sample of CSF.<br />
• The sample of CSF is sent to a laboratory, where the bacteria<br />
can be cultured and identified.<br />
• 3 tubes of CSF are collected<br />
• One for chemistry analysis for glucose & protein levels and<br />
cell count<br />
• One for microbiology analysis for Gram stain, bacterial<br />
culture…<br />
• One for cytology analysis<br />
• It will help doctors distinguish between the different type of<br />
meningitis.
CONDITION GLUCOSE PROTEIN CELLS<br />
<strong>Bacterial</strong> meningitis Low High High<br />
(>300/mm³)<br />
Viral meningitis Normal Normal or<br />
high<br />
Mononuclear<br />
(
• Antimicrobial susceptibility testing should be performed on all<br />
clinically relevant bacteria isolated from CSF, so that the<br />
antibiotic therapy that was started immediately can be<br />
adjusted if necessary.<br />
Diagnosis (cont.)<br />
• Culture media used for bacterial culture of CSF are:<br />
• 5% sheep blood agar<br />
• Enriched chocolate agar<br />
• Enrichment broth (eg, thioglycolate)<br />
• Culture plates should be incubated in an atmosphere<br />
containing 5 to 10% CO2.
Diagnosis (cont.)<br />
• METHODS FOR DETECTING BACTERIA IN CSF:<br />
• Gram staining<br />
• Acridine orange stain<br />
• Fluorochrome stain (bacteria appear bright red)<br />
• More sensitive than gram stain<br />
• Reduction in the time of examination of CSF smear<br />
• Requires fluorescence microscope<br />
• Wayson stain<br />
• Simple & sensitive stain for screening CSF smears for<br />
bacteria<br />
• Bacteria appear dark blue
Diagnosis (cont.)<br />
• Quellung procedure (Quellung capsular reaction)<br />
• Used to confirm presence of S.pneumoniae,<br />
N.meningitidis, or H.influenzae<br />
• Antisera specific for the capsular polysaccharides of each<br />
of these 3 bacteria are mixed with separate portions of<br />
clinical specimens.<br />
• Formation of Ag/Ab complexes on the surfaces of these<br />
bacteria induces changes in the refractive indices of their<br />
capsules.<br />
• The capsules appear clear & swollen.
Diagnosis (cont.)<br />
• METHODS FOR DETECTING BACTERIAL ANTIGENS:<br />
• CIE (counterimmunoelectrophoresis)<br />
• COAG (coagglutination)<br />
• LA (latex agglutination)<br />
• OTHER METHODS USED:<br />
• EIA (enzyme immunoassays)<br />
• LAL Assay (limulus amebocyte lysate assay)<br />
• GLC (gas-liquid chromatography)<br />
• PCR (polymerase chain reaction)
Complications<br />
If the disease is left untreated, the following manifestatations are seen:<br />
• Increased spinal fluid pressure<br />
• Myocarditis: inflammation of the heart<br />
• Hydrocephalus (blockage of spinal fluid in brain)<br />
• Mental retardation<br />
• Deafness :Loss of hearing from infiltration of the 8th nerve<br />
• Brain damage:Spread from the meninges to the brain is called<br />
meningoencephalitis<br />
• Severe diarrhea and vomiting<br />
• Internal bleeding<br />
• Low blood pressure<br />
• Shock<br />
• Death
Complications<br />
• Waterhouse-Friderichsen syndrome<br />
• Adrenal gland failure due to bleeding into the adrenal<br />
gland.<br />
• Symptoms include acute adrenal gland insufficiency and<br />
profound shock. It is deadly if not treated immediately
Treatment<br />
• Because bacterial meningitis is a medical emergency, it's<br />
important to start the treatment as soon as it is diagnosed or<br />
even suspected.<br />
• <strong>Bacterial</strong> meningitis is treated with antibiotics. The doctor will<br />
start intravenous (IV) antibiotics with a corticosteroid (eg,<br />
Dexamethasone) to bring down the inflammation before all<br />
the test results are even known. When the specific bacteria are<br />
identified, he may decide to change antibiotics or not.<br />
• In addition to antibiotics, it is important to replenish fluids lost<br />
from fever, loss of appetite, sweating, vomiting and diarrhea.
Treatment (cont.)<br />
• Some patients may need to stay in the hospital, depending on<br />
the severity of the illness and the treatment needed.<br />
• Complications can require additional treatment.<br />
• Anticonvulsants (eg, Diazepam or Phenytoin) might be given<br />
for seizures.<br />
• Additional IV fluids in case of shock or low blood pressure.<br />
• Supplemental oxygen or mechanical ventilation if the child<br />
has difficulty breathing.<br />
• All neonates should have a hearing test following their<br />
recovery to screen for hearing impairment.
Microorganism<br />
Recommended<br />
therapy<br />
Duration of<br />
treatment<br />
Streptococcus<br />
pneumoniae<br />
Neisseria<br />
meningitidis<br />
Penicillin G or Ampicillin<br />
OR<br />
Vancomycin + Thirdgeneration<br />
cephalosporin<br />
(eg, ceftriaxone or<br />
cefotaxime)<br />
Penicillin G<br />
OR<br />
Third-generation<br />
cephalosporin (eg,<br />
ceftriaxone or cefotaxime)<br />
2 weeks<br />
7 days
Haemophilus<br />
influenzae<br />
Third-generation<br />
cephalosporin (eg,<br />
ceftriaxone or cefotaxime)<br />
7 days<br />
Listeria<br />
monocytogenes<br />
Ampicillin or Penicillin G<br />
3 weeks<br />
Escherichia coli<br />
Third-generation<br />
cephalosporin (eg,<br />
ceftriaxone or cefotaxime)<br />
21 days or 2 weeks<br />
Group B<br />
streptococci<br />
Ampicillin or Penicillin G<br />
14-21 days
Prognosis<br />
• If treated immediately, most patients who have acute bacterial<br />
meningitis recover fully.<br />
• But when diagnosis or treatment is delayed, permanent brain<br />
damage or death becomes more likely, especially in very young<br />
children and older people.<br />
• Some patients develop seizures that require lifelong treatment.<br />
• Even with appropriate treatment, about 5-15% patients die<br />
from bacterial meningitis.<br />
• 10-20% of patients who survive bacterial meningitis have brain<br />
damage, hearing problems, or developmental difficulties<br />
(especially in children).
Prevention<br />
• Cases of bacterial meningitis should be reported to state<br />
or local health authorities so that they can follow and<br />
treat close contacts of patients and recognize outbreaks.<br />
• Overseas travelers should check to see if meningococcal<br />
vaccine is recommended for their destination. Travelers<br />
should receive the vaccine at least 1 week before<br />
departure, if possible.
Prevention (cont.)
Prevention (cont.)<br />
IMMUNIZATION:<br />
• Haemophilus influenzae type b (Hib) vaccine<br />
• Part of the recommended immunization schedule in<br />
children.<br />
• 3 doses given at 2, 4 and 6 months of age, a booster dose is<br />
given at 12-15 months of age.<br />
• Pneumococcal conjugate vaccine (PCV7)<br />
• Recommended for children under 2-5 years old who are at<br />
high risk of pneumococcal disease (weak immune system).<br />
• 4 doses given at 2, 4, 6 and 12-15 months of age.
Prevention (cont.)<br />
• Pneumococcal polysaccharide vaccine (PPV)<br />
• Recommended for adults >65 and children >2 years who<br />
have long-term health problems.<br />
• 1 dose is given (under some circumstances a 2nd dose may<br />
be given).<br />
• Meningococcal conjugate vaccine (MCV4)<br />
• Recommended for children from 11 to 18 years who<br />
haven't yet been vaccinated, who are at high risk of bacterial<br />
meningitis, for microbiologists, for overseas travelers.<br />
• 1 dose is given.
Prevention (cont.)<br />
CHEMOPROPHYLAXIS:<br />
• Rifampin is given to family members of an infected person to<br />
reduce their risk of contracting the disease as H influenzae can<br />
persist in the nasopharyngeal secretions even after a successful<br />
treatment.<br />
• Pregnant women should not take rifampin as it may harm the<br />
fetus. They should be treated with single doses of ciprofloxacin,<br />
azithromycin, or ceftriaxone.
Tuberculous meningitis<br />
DEFINITION:<br />
• Infection of the meninges caused by Mycobacterium<br />
tuberculosis (acid-fast Gram-positive mycobacterium), the<br />
bacteria that causes tuberculosis.<br />
• It is the most severe form of tuberculosis.<br />
• It is caused by the spread of Mycobacterium tuberculosis to<br />
the brain, from another site in the body. Infection begins in the<br />
lungs and may spread to the meninges by a variety of routes.
Tuberculous meningitis (cont.)<br />
EPIDEMIOLOGY:<br />
• In areas with much tuberculosis,<br />
• tuberculous meningitis usually affects young children<br />
• it develops after the primaty tuberculosis infection<br />
• In areas with less tuberculosis,<br />
• tuberculous meningitis tends to strike adults.<br />
• it is due to reactivation of an old focus of tuberculosis that<br />
had been dormant
Tuberculous meningitis (cont.)<br />
RISK FACTORS:<br />
• history of pulmonary tuberculosis<br />
• excessive alcohol use<br />
• AIDS<br />
• other disorders that compromise the immune system
Tuberculous meningitis (cont.)<br />
SYMTOMS: (usually begin gradually)<br />
• Fever<br />
• Sluggishness<br />
• Loss of appetite<br />
• Severe headache<br />
• Nausea and vomiting<br />
• Stiff neck<br />
• Sensitivity to light (Photophobia)<br />
• Loss of consciousness
Tuberculous meningitis (cont.)<br />
DIAGNOSIS:<br />
• CSF analysis<br />
• Chest radiography<br />
• CT scan or MRI<br />
• Sputum examination<br />
• Sputum culture<br />
• Tuberculin skin testing
Tuberculous meningitis (cont.)<br />
TREATMENT:<br />
• If tuberculous meningitis is seriously suspected, treatment<br />
should start immediately.<br />
• Start with 2 month intensive course of isoniazid, rifampin,<br />
pyrazinamide, and ethambutol followed by 4 months of<br />
isoniazid and rifampin.<br />
• The use of the corticosteroid (eg, dexamethasone) improves<br />
survival but probably does not prevent severe disability.<br />
• The hydrocephalus (accumulation of CSF in the brain) may<br />
require placement of a ventriculoperitoneal shunt.
Tuberculous meningitis (cont.)<br />
COMPLICATIONS:<br />
• Brain damage which may cause<br />
• motor paralysis<br />
• seizures<br />
• mental impairment<br />
• abnormal behavior<br />
• Cerebral ischemia ( anterior circulation most commonly)<br />
• Mesencephalic infarction<br />
• Syringomyelia ( disorder in which a cyst or tubular cavity<br />
forms within spinal cord)
Prognosis of TB meningitis<br />
• Fatal if untreated<br />
• It causes severe neurologic deficits or death in >50%<br />
of cases<br />
• Long-term follow up is necessary to detect<br />
recurrences
Tuberculous meningitis (cont.)<br />
PREVENTION:<br />
• BCG vaccine (given at birth)<br />
• PPD (Purified Protein Derivative) Tuberculin test determines if<br />
someone has developed an immune response to M.<br />
tuberculosis<br />
• 0.1mL injected immediately under the surface of the skin of<br />
the forearm<br />
• Test should be read between 48 and 72 hours after the<br />
injection for induration (hardness)<br />
• Classified as positive based on the diameter of the<br />
induration
Bibliography<br />
• http://www.cdc.gov/ncidod/DBMD/diseaseinfo/meningococcal_g.htm<br />
• http://www.umm.edu/altmed/articles/meningitis-000106.htm#Following%20Up<br />
• http://www.wrongdiagnosis.com/b/bacterial_meningitis/intro.htm<br />
• http://www.immunize.org/searchiac3/searchiac3.asp?zoom_cat=-<br />
1&zoom_and=1&zoom_per_page=10&zoom_query=bacterial+meningitis<br />
• http://www.clevelandclinic.org/health/health-info/docs/3300/3384.asp?index=11039<br />
• http://www.dhpe.org/infect/Bacmeningitis.html<br />
• http://www.emedicine.com/PED/topic198.htm<br />
• http://www.nlm.nih.gov/medlineplus/ency/article/000680.htm<br />
• http://www.kidshealth.org/parent/infections/lung/meningitis.html<br />
• http://www.meningitisuk.org/about-meningitis/bacterial-meningitis/frequently-askedquestions.htm<br />
• http://www.meningitisuk.org/about-meningitis/bacterial-meningitis/frequently-askedquestions.htm<br />
• http://www.guideline.gov/summary/summary.aspx?ss=15&doc_id=5946&nbr=00391<br />
5&string=bacterial+AND+meningitis
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