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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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