APPLIED

THERAPEUTIC II
FAR 454/3
TOPIC: MENINGITIS

GROUP 1
1. AHMAD KAMAL ARIFFIN BIN ABDUL JAMIL UF070001
2. CHANG YEN MEAI 90299
3. FATHIEN NAJJIHAH BINTI A AZIZ UF070004
4. JURIAH MOHAMED ISMAIL  85218
5. LIM KOK HAN 95298
6. NAZIRA BEGUM BT MOHAMED IQBAL UF070010
7. NURSYAHIDA BT AHMAD UF070011
8. MOHD SHAFIQ AKMAL BIN OMAR 95312
9. SULESA BINTI UTOK 95367
10. THAMRON KEOWMANI A/L EH SAU 95381
11. PUVANESVARAN A/L NARAINAN 95355

LECTURER: Ms.Nur Hafzan Md Hanafiah

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 TOPIC: MENINGITIS (GROUP 1)

1) Define abbreviations and technical terms.

a) CC Chief complaint
b) PTA Prior to admission
c) ED Emergency Department
d) HPI History of present illness
e) FH Family History
f) SH Social History
g) QID 4 times a day
h) NKDA No known drug allergy
i) ROS Review of system
j) PE Physical examination
k) VS Vital signs
l) BP Blood pressure
m) HEENT Head, eyes, ears, nose and throat
n) PERLLA Pupils equal, round, and react to light and accommodation
o) EOMI Extraocular movements (muscles) intact
p) JVD Jugular venous distension
q) RRR Regular rate and rhythm
r) CTA Clear to auscultation
s) ABD Abdomen
t) NT/ND Non-tender, non-distended
u) BS+ Bowel sound positive
v) A&O Alert and oriented
w) EXT Extremities
x) CCE Clubbing, cyanosis, edema
y) KVO Keep vein open

2) What signs, symptoms, and laboratory values are consistent with meningitis in this
patient?

Signs:
- nuchal rigidity (neck stiffness - Stiffness in the nape of the neck, often accompanied by pain
and spasm on attempts to move the head; the most common sign of meningitis)
- fever

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Symptoms:
-neck stiffness, photobhobia(eye discomfort in exposure to bright light), headache, vomiting
-skin rash/aches
-others: complained of myalgias, arthralgias, aching over her neck
Laboratory CSF WBC 850/mm3 (>500/mm3) elevated
values CSF Glucose 32mg/dL(<50% serum glucose) lowered
CSF Protein 94mg/dL (> 50 mg/dL) elevated

3) What other clinical features not identified in this patient?

Several clinical signs facilitate the diagnosis of meningitis. Kernig’s sign and Brudzinski’s
sign are easy to elicit and can alert physicians to the precarious situation of a patient with
meningitis. Both of these signs are thought to be caused by the irritation of motor nerve roots
passing through inflamed meninges as the roots are brought under tension.
 Brudzinski’s sign
– Flexing the patient’s neck causes flexion of the patient’s hips and knee
 Kernig’s sign
– Flexing the patient’s hip 90 degrees then extending the patient’s knee causes pain.

Others: mental confusion (altered mental status), N/V, sleepiness, cyanosis (bluish skin),
etc

4) Discuss possible causes: (septic or aseptic)

There are two types of meningitis - viral (also called aseptic) and bacterial (septic). Many kinds
of viruses can cause viral meningitis, especially enterovirus. Only a few kinds of bacteria cause
bacterial meningitis. A sample of spinal fluid, usually collected by a spinal tap, is needed to find
out if someone has meningitis and to see what caused it.
Viral meningitis is the most common form. It is usually less severe.
Bacterial meningitis even though less common, but is very serious. The bacteria can destroy the
tissue that they infect and cause a lot of complications. A virus or bacteria can enter the body

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through the nose or mouth and travel to different places in the body. For most people, this causes
an infection in the nose, throat or ear. It becomes meningitis when the virus or bacteria travels
through the bloodstream to the brain and spinal cord and infect the meninges (the protective
tissue layers lining the brain’s internal structures)

Septic (bacterial) meningitis is commonly caused by the following 3 causative agents:

(accounted for ~ 80% of cases caused by bacterial)
Neisseria meningitidis - causes illness in people of any age called “meningococcal.”. The
bacteria are spread through saliva during kissing, sharing of food, drinks or cigarettes, and by
close contact with infected people who are sneezing or coughing.

Haemophilus influenzae type b bacteria, called Hib, can also cause meningitis. There is a
vaccine called “Hib vaccine” that prevents infants and young children from getting Hib disease.
Certain people who have come in close contact with the saliva of a person with meningitis from
this type of bacteria may need antibiotic.

Streptococcus pneumoniae are bacteria that cause lung and ear infections but can also cause
“pneumococcal” meningitis. Most people who have these bacteria in their throats stay healthy.
However, people with comorbidities or with weakened immune systems, and those who are very
young or very old, are at higher risk for getting pneumococcal meningitis. Meningitis caused by
Streptococcus pneumoniae is not spread from person-to-person.

Other bacteria can also cause meningitis, but meningitis from these other bacteria is much less
common and usually not contagious.

Aseptic meningitis
A group of viruses called enteroviruses is the most common cause(account for 85-95% ) of viral
meningitis, where infant & young children is the common victim. These viruses are found in the
throat and feces of infected people. The virus is most likely to be spread when people do not
wash their hands after using the toilet or changing a diaper or soiled sheets, then touch their own
mouths, prepare food for others, or touch others with their contaminated hands. These viruses

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can also be spread by the kind of close face-to-face contact. Many enteroviruses don’t cause
people to feel very sick. Others may cause only mild diarrhea or vomiting. In the vast majority of
cases the illness resolves itself within a week without any complications or need for specific
treatment.
Example:
 MUMPS VIRUS in an unimmunized population, mumps is one of the most common
causes of aseptic meningitis and encephalitis. Cases of vaccine-associated mumps
meningitis have also been reported.
 HIV VIRUS can infect the meninges early and persist in the CNS after initial infection
 HERPESVIRUSES: Overall, herpes simplex viruses account for approximately 0.5 to 3%
of all cases of aseptic meningitis.
 Cytomegalovirus and Epstein-Barr virus may cause aseptic meningitis in association with
a mononucleosis syndrome, particularly in an immunocompromised host.

However, aseptic meningitis can also be caused by bacteria, fungi, or parasites.

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From: http://emedicine.medscape.com/article/232915-overview

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 4) Discuss presence or absence of risk factors for bacterial meningitis

Presence of risk factors for bacterial meningitis

a. Age
Patient at age of 20 yo may prone to infection by N meningitides, S pneumoniae (most
common) & Haemophilus influenzae

b. IV drug use
IV drug use may increase the chance of bacterial infections. In this case, patient is on IV
hydration and IV Ketorolac 30mg before she was discharged.

c) Community setting.
Infectious diseases tend to spread quickly wherever larger groups of people gather together.
As a result, college students living in dormitories (as in this case), military personnel and
children in childcare facilities are at an increased risk.

Absence of risk factors for bacterial meningitis

 Pregnancy: Pregnant women are at an increased risk of getting listeriosis. The bacteria
that cause listeriosis, listeria bacteria, can also cause meningitis.
 Working with animals: Dairy farmers, ranchers, and other people who work with
domestic animals are at an increased risk of contracting listeriosis which can also cause
meningitis.
 Weakened immune system(immunosuppressed individual)
There are certain diseases, medications and surgical procedures that may weaken the
immune system and increase risk of meningitis.

 Others: absence of concurrent upper respiratory tract infection, HIV infection, active and
( passive )smoking, household exposure

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 6) Devise a problem list for this patient.

Main problem: meningitis

Patient is presented with the signs and symptoms of meningitis, most probably bacterial
meningitis based on lab data & presenting symptoms (fever, rash, headache, etc)

Findings: Bacterial Meningitis Findings: Viral Meningitis

CSF Color: Cloudy CSF CSF Color: Clear to Cloudy Fluid

CSF Glucose much less than 50 CSF Glucose: Normal (50-80mg/dl)

CSF Protein much greater than 45 CSF Protein > 45 (normal 20-45mg/dl)

CSF Leukocytes: Markedly CSF Leukocytes: Increased

increased Neutrophils CSF Lymphocytes

CSF Opening Pressure: increased >200 CSF Opening Pressure: Normal or

increased

Associated problems: pain, skin rashes (aching), light sensitivity, headache, etc

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7) What are the treatment goals for this patient?

The goals of treatment are:

1) eradication of infection
2) amelioration of signs and symptoms(fever, rashes, headache, etc)
3) preventing of neurologic sequelea such as seizures, deafness, coma, death
4) to prevent disease progression and subsequently the complication and mortality

8) Suggest therapeutic alternatives for empiric treatment of meningitis for this

patient?
Suspected individual of 2–50 years-most commonly N . meningitidis, S. pneumoniae
Empirical treatment: Vancomycin plus a third-generation cephalosporin (ceftriaxone or
cefotaxime)

Recommended dose (adult) : cefotaxime (total daily dose: 8–12 g (4–6 hourly))
OR ceftriaxone (4 g/daily (12–24 hourly))
+
vancomycin 30–45 mg/kg/day (8–12 hourly)
(TDM?? Maintain serum trough concentrations of 15–20
mg/mL)

Reference : ISDA Guidelines

http://www.uphs.upenn.edu/bugdrug/antibiotic_manual/idsameningitisNov04.pdf

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 Initial treatment was started as follows:
IV Cefotaxime 2g q6h x 10 days
IV Vancomycin 500mg q6h x 10 days
D5W/0.2% NaCl +20mEq/L KCl at 40cc/hr for 24hours, then KVO

9) Discuss the rationale for the above treatment.

Most studies showed that longer the duration of symptoms in patients with bacterial
meningitis, the more likely the possibility of experiencing an adverse outcome-thus empirical
treatment is vital as any delay in administration of antimicrobial therapy might be associated
with an adverse clinical outcome due to increased progeny of infectious organism.

The third-generation cephalosporins (the agent chosen in this case is cefotaxime) are the
preferred empirical treatment on admission. It’s quite effective in meningitis especially those
caused by aerobic gram-negative bacilli with cure rates of 78%–94% have been reported
Most clinical practices recommended a combination of 3rd Gen cephalosporin (cefotaxime or
cefriazone) plus a vancomycin for empirical treatment until the definitive causative organism
is confirmed.
Cefotaxime is known to have good cerebrospinal fluid penetration while vancomycin has
broad spectrum activity to cover the commonly suspected organism.

D5W/0.2% NaCl is administered to restore fluid /electrolyte level. KCl is given to restore
electrolyte level probably because the Cl value suggests that patient is dehydrated.

**Extra info:
For patients with immediate penicillin or cephalosporin hypersensitivity, use:
(i) vancomycin 12.5 mg/kg up to 500 mg (child <12 years: 15 mg/kg up to 500 mg) IV, 6-hourly
PLUS
(ii) ciprofloxacin 400 mg (child: 10 mg/kg up to 400 mg) IV, 12-hourly
OR
(iii) moxifloxacin 400 mg (child: 10 mg/kg up to 400 mg) IV, daily.

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10) The CSF culture was reported as positive for N.meningitides only. Blood cultures
showed no growth. Based on this new information, what is your response with
regards to antimicrobial therapy for this patient?

Standard treatment: Benzylpenicillin(Pen G) 4 mega units IV q 4-6hours for 7-10 days is the
preferred treatment for N.meningitidis.
Alternative treatment: third generation Cephalosporins (Ceftriaxone or cefotaxime)-duration
7-10 days

3rd generation cephalosporins

Cefotaxime 200 mg/kg/24hour IV in 3 divided doses (max:12/day)
(Usual dose: 2g q8hour) OR
Ceftriaxone 50-100 mg/kg/24hour IV in 2 divided doses (max:4g/day)
(Usual dose: 2g q12hour)

For this case, patient should be continued with previous treatment of IV Cefotaxime 2g q6h
provided she shows good response or change to benzylpenicillin, if otherwise.

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 11) What monitoring parameters are used to assess therapeutic efficacy and to detect
complications from the infection or treatment?

To assess therapeutic efficacy:

-monitor temperature (every 4-6hours), WBC with differential(daily), HR, RR, oxygen
saturation, urine output, mental status changes, blood pressure, CSF culture, electrolyte
assessment, Blood and CSFs’ glucose, protein, CBC (Complete Blood Count), urea, Cr, LFTs,
lactate etc
-improvement/resolution of sign/symptoms of meningitis over the period of therapy (assess
pain, fever, skin rashes, etc)
-maintaining fluid balance-monitor output and input

Evaluation: expected outcomes:

-afebrile, adequate urine output, CVP in normal range, alert mental status, normal vital signs,
pain controlled and optimal level of functioning after resolution.

To detect complications from the infection or treatment:

 Monitor patients for potential adverse effects of medications, such as hypersensitivity

reactions, cytopenia, or liver dysfunction-monitor LFT
 Assess neurologic status and vital signs
 Assess sensorineural status (hearing and vision), diminished cognitive functions
 Monitor/assess risk for deficient fluid volume, ineffective tissue perfusion(monitor CVP
frequently ), etc
 Obrserve signs/symptoms of ICP(dilated pupils, widening pulse pressure, etc)
 Coagulopahty : assess PT, Aptt, signs of bleeding, etc
 Drug-level monitoring may be needed for some antibiotics such as vancomycin and the
aminoglycoside

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Self-study:

1) Role of corticosteroid therapy in meningitis

-The rationale for use of adjunctive corticosteroid (commonly used agent: dexamethasone) in
certain patients with suspected or proven bacterial meningitis is that the subarachnoid space
inflammatory response during bacterial meningitis is a major factor contributing to morbidity and
mortality. Attenuation of this inflammatory response may be effective in decreasing many of the
pathophysiologic consequences of bacterial meningitis, such as cerebral edema, increased
intracranial pressure, altered cerebral blood flow, cerebral vasculitis, and neuronal injury, as
mediated by proinflammatory cytokine expression.

-Animal studies and clinical trials have demonstrated that adjunctive corticosteroid therapy
reduces the production of cytokines in the CSF resulting in decreased severity of the
inflammatory process and fewer neurologic sequelae. These data support the use of adjunctive
dexamethasone in infants and children with S. pneumoniae and H. influenzae type B (HiB)
meningitis. There is not sufficient evidence supporting the use of adjunctive corticosteroid
therapy in children with meningitis caused by N. meningitidis. Also, the routine use of
dexamethasone in adult meningitis cannot presently be recommended- thus need careful
monitoring for the possibility of GIT bleeding.

2) Need for prophylaxis

This prophylaxis is necessary because the germs that cause meningitis are spread easily from
person to person by direct contact. This may include: sharing a pacifier, toothbrush, eating
utensils, or drinking glasses, drooling, shaking hands, kissing, breathing, sneezing or coughing
on someone. The virus may also be found in the stool of the infected person

Frequent handwashing with soap and water or use of alcohol-based hand rubs or gels can help
stop the spread of many viruses and bacteria. Not sharing food, drinks, or eating utensils with
other people can also may help.

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For some causes of meningitis, prophylaxis can be provided in the long term with vaccine, or in
the short term with antibiotics

There are 5 vaccines that can help prevent meningitis:

• Haemophilus influenzae (Hib) vaccine is usually given at 2, 4, 6 and between 12 and 15 months
of age.

• Pneumococcal conjugate vaccine 7-valent (PCV7) is recommended for all children less than 24
months old and in certain high-risk children between the ages of 24 and 59 months.

• Pneumococcal polysaccharide vaccine 23-valent (PPV23) is used in high-risk individuals 2

years of age or older. (High-risk children less than 5 years of age should also receive PCV7.)
This vaccine is also recommended for everyone 65 years of age and older.

• Meningococcal polysaccharide vaccine - for use in people 2 years of age and older and
provides protection for about 3-5 years.

• Meningococcal conjugate vaccine- is approved for use in people 11-55 years of age and is
expected to help decrease disease transmission and to provide more long-term protection.

-In cases of meningococcal meningitis, prophylactic treatment of close contacts with antibiotics
(e.g. rifampicin, ciprofloxacin or ceftriaxone) can reduce their risk of contracting the condition,
but does not protect against future infections.

References for self-study question:

http://www.uphs.upenn.edu/bugdrug/antibiotic_manual/idsameningitisNov04.pdf

http://www.ncbi.nlm.nih.gov/pubmed/8588129?dopt=Abstract

http://www.nejm.org/doi/full/10.1056/NEJMc076554

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