MENINGITIS

PYOGENIC
MENINGITIS
PREMILA PALANIANDY
012014100157
OUTLINE
1)Definition
2)Etiology
3)Pathogenesis
4)Clinical Features
DEFINITION
Inflammation of the meninges of te brain
Caused by bacterial infection
Bacterial meningitis
ETIOLOGY
1)Neisseria meningitidis
Gram negative cocci
capsulated
Non motile
Serogruops A,B,C,Y,W135
• 90% of infection
2)Streptococcus pneumoniae
Gram positive
Capsulated
Lanceolate diplococci
3)Haemophilus influenzae Type B
Gram negative bacilli
Capsulated
Six different serotypes(a-f)
Common in children
4)Listeria monocytogenes
Gram positive
Bacillus
Immunocompromised adults
-renal transplant,cancer patients
PATHOGENESIS
1)Mode of transmission
-direct contact
-respiratory droplets from nose
and throat of infected people
Bacteria reach
CNS Brain death

Bacterial
Raised intracranial
multiplication
pressure

Inflammatory
response Cerebral edema

Endothelial Disruption of blood

damage brain barrier
CLINICAL FEATURES

fever rash

confusion
Nausea and vomitting
COMPLICATION
1)Brain abscess
2)Hearing loss
3)Cranial nerve palsies
SUMMARY
1)Pyogenic meningitis:
a)Neisseria meningitidis
b)Streptococcus pneumoniae
c)Haemophilus influenzae Type B
d)Listeria monocytogenes
2)Clinical features
-fever,rash,confusion
3)Complication
-hearing loss,brain abscess
MENINGITIS
PART 2
NURUL SOLEHAH BINTI BAHARUDIN
012014100068
OUTLINES
Viral meningitis
Tuberculous meningitis
Fungal meningitis
Parasitic meningitis
Clinical features
VIRAL MENINGITIS
most common type of meningitis
tends to be less severe, rarely last for more than a week and
most people recover completely
Affects children and adults under age 30
Most infections occur in children under age 5
Enterovirus (Echovirus,
Coxsackievirus, Polio virus)
Herpes simplex virus type 2
Mumps and measles virus
Lymphocytic choriomeningitis
Arbovirus
• Japanese encephalitis virus
• Eastern and Western equine encephalitis
HIV
ROUTES
Enteroviruses - Usually through the oral-fecal route, but also
sometimes through the respiratory route
Arboviruses - Via blood-sucking arthropods, usually
mosquitoes
Lymphocytic choriomeningitis virus - Through contact with
rodents (eg, hamster, rats, mice) or their excreta
ENTEROVIRUS
commonest in children aged 5–14 years, but also occurs in
other age groups.
Echovirus infection
• The commonest cause of enteroviral meningitis.
• The predominant serotypes are 6,9, 11, 19 and 30.
There are annual epidemics in the late summer
presenting as so-called ‘summer flu’, with fever,
sore throat and often headache.
• A proportion of infected individuals develop
meningitis, with or without a preceding or
accompanying sore throat.
ENTEROVIRUS
MENINGITIS
Coxsackievirus meningitis
• caused predominantly by serotypes A9, B4 and B5.
• Type A infections affect all age groups
• Type B disease occurs mainly in infants and pre-school
children.
Enteroviruses can cause a rare, generalized chronic brain
infection in individuals with agammaglobulinaemia.
ENTEROVIRUS
MENINGITIS

Polio virus
• 3 serotypes (1,2,3)
• Pathogenesis
• Enters the body through the alimentary tract
and oropharynx
• followed by a viraemic phase during which the
virus enters the meninges and spinal cord.
• The virus infects and kills anterior horn cells,
leading to lower motor neurone degeneration
HERPES SIMPLEX
TYPE 2

Almost always associated with primary genital herpes

simplex, of which it is a complication.
Occasional cases occur in the absence of detectable
genital lesions.
The meningitis is benign, behaving like an enteroviral
infection, but may be treated with aciclovir if the
diagnosis is known before resolution occurs.
Mollaret’s recurrent meningitis is caused by relapsing
attacks of herpes simplex meningitis.
ARBOVIRUS
Arthropod borne viruses
Vector borne
• Mosquito
• Tick
Route of infection
• Replication in insect vector
• Exposure via cutaneous contact
• Respiratory transmission experimentally
demonstrated
• Local replication followed by viremia
TUBERCULOUS
MENINGITIS
meningitis associated with acute miliary
tuberculosis
Most severe form of TB
Causes severe neurologic deficits or
death in more than half of cases
In areas with a high prevalence of TB,
meningitis tends to be most commonly
seen in children from 0-4 years
TB less frequent, most meningitis cases
are in adults
TUBERCULOUS
MENINGITIS

Gradual onset over a few weeks

Occasionally, the onset is much more
rapid and may be mistaken for a
subarachnoid hemorrhage
Spinal TB is uncommon now except in
resource poor country ; bacteria in the
vertebrae destroy the invertebral disks to
form epidural abscess which compress
the spinal cord and leads to paraplegia
 FUNGAL MENINGITIS
Rare
Insidious onset
Has historyof lung infection
Risk factor:
• immunocompromised people (disease,
medication)
• Premature babies with very low birth weights
(Candida)
• African American, Filipinos, 3rd trimester
pregnant women (Coccidiodes infection/valley
fever)
FUNGAL MENINGITIS
Cryptococcus neoformans – most common
Coccidiodes immitis -Occurs in <1% of infected individuals
but fatal unless treated
Histoplasma
Mucormycosis
Aspergillus
Candida
 FUNGAL
MENINGITIS
Routes of infection of fungi
Cryptococcus -inhaling soil contaminated with bird
droppings.
Histoplasma - environments with heavy contamination of
bird or bat droppings, particularly in the Midwest near the
Ohio and Mississippi Rivers.
Blastomyces - exist in soil rich in decaying organic matter
in the Midwest United States, particularly the northern
Midwest.
Coccidioides - soil of endemic areas (Southwestern US
and parts of Central and South America).
Candida - acquired in hospital setting
PARASITIC MENINGITIS
free-living amoebas is an infrequent but
often life-threatening human illness.
It’s more common in underdeveloped
countries and usually is caused by
parasites found in contaminated water,
food, and soil
The most common causative agents
are:
• Free-living amoebas (ie, Acanthamoeba,
Balamuthia, Naegleria)
• Helminthic eosinophilic meningitis
 CLINICAL SYMPTOMS IN
ADULT
Fever
Headache
Stiff neck (Brudzinski’s sign)
Nausea
Vomiting
Sensitivity to bright light
Sleepiness or trouble waking
up from sleep
Lack of appetite
Lethargy
Kernig’s sign
 CLINICAL FEATURES IN
CHILDREN
Flu –like symptom
Fever
Poor feeding
lethargy
Bulging fontanelle.
Vomiting.
Strange high-pitched
cry.
Convulsions.
Opisthotonus.
REFERENCES
Mim’s medical microbiology
Infection Microbiology and Management
http://www.slideshare.net/sid469/meningitis-
25933236?qid=4bd12b44-ab1f-49e3-8ace-
4b0237ae78d0&v=&b=&from_search=1
http://www.cdc.gov/meningitis/viral.html
http://www.cdc.gov/meningitis/fungal.html
http://www.slideshare.net/blackempress/meningitis-in-
children?qid=4bd12b44-ab1f-49e3-8ace-
4b0237ae78d0&v=&b=&from_search=2
LAB
DIAGNOSIS
NURUL NABILAH BINTI MOHD
SHAARI AZYZE
012014100143
LAB DIAGNOSIS

CSF EXAMINATION
PRESUMPTIVE IDENTIFICATION
• GRAM STAINING
• LATEX AGGLUTINATION
• RAPID DIAGNOSTIC TEST
CULTURES
POLYMERASE CHAIN REACTION
SEROLOGIC DIAGNOSTIC
CSF
EVALUATION
 NORMAL BACTERIAL VIRAL FUNGAL TUBERCULOUS

CSF EVALUATION
Opening
Pressure
(MmH2O)
50-180 Elevated Normal Variable Variable

0-5 Cells
Leukocyte (Adults /
Count Children) >500 Cells <100 Cells 100-500 Cells 100-500 Cells
(Cells/µl ) Up To 30 Cells
(Newborn)
- 60-70%
Lymphocytes
Predominance Early
- 30%
Of Neutrophils Neutrophils,
Cell Differential Monocytes And Lymphocytes Lymphocytes
(PMN's) Late
Macrophages
Lymphocytes
- 2% Other
Cells

Protein (Mg/dL) 15 – 45 >250 <100 10-50 10-50

Glucose
40-85 <40 Normal <40 <40
(Mg/dL)

Normal;
Appearance Colorless And Turbid Clear Fibrin Web Fibrin Web
Clear

Culture Sterile Positive Negative

CSF collection
Lumbar Puncture
CSF collection
Subdural Tap
CSF collection
Ventricular Aspiration
PRESUMPTIVE
IDENTIFICATION
 GRAM STAINING
 LATEX AGGLUTINATION
 RAPID DIAGNOSTIC TEST
GRAM
STAINING
NESSERIA
MENINGITIDIS

Gram-negative,
coffee-bean shaped diplococci
STREPTOCOCCUS
PNEUMONIAE

Gram-positive, lanceolate diplococci,

sometimes occurring in short chains.
HAEMOPHILUS
INFLUENZAE

Small, pleomorphic
Gram-negative coccobacilli
CRYPTOCOCCAL
MENINGITIS

India ink stain Silver stain

• Double refractile • Budding capsulated
spherules with clear yeast
halo
LATEX
AGGLUTINATION
• Detect certain antigens or
antibodies in a variety of
bodily fluids such as blood,
saliva, urine or cerebrospinal
fluid.
• Positive reaction :
agglutination of the latex
particles and slight clearing of
the suspension occurs within
2-10minutes.
• Negative reaction : the
suspension remains
homogenous and milky in
appearance.
RAPID DIAGNOSTIC
TEST

• RDTs have been developed for direct testing of CSF

specimens without prior heat or centrifugation.
• The test is based on the principle of vertical flow
immunochromatography in which gold particles and
nitrocellulose membranes are coated with monoclonal
antibodies to capture soluble serogroup-specific
polysaccharide antigens in the CSF.
• The test consists of 2 duplex paper sticks (also called
dipsticks).
READING OF RDT

• Red lines on the dipsticks will indicate whether one

of the four meningococcal serogroups has been
detected in the CSF.
• The upper line on the dipstick is the positive control
and should always be present.
• Positive result : lower red line will also be present.
• Negative result : single upper pink control line only.
READING OF RDT
OTHER LAB
DIAGNOSTIC
TEST
 CULTURE
 POLYMERASE CHAIN REACTION
CULTURE
NESSERIA
MENINGITIDIS
• Growth on both chocolate agar and
blood agar
• Young colonies : round, smooth,
moist, glistening, and convex, with a
clearly defined edge on a BAP.
• Actively growing colonies : grey and
unpigmented on BAP
• Older cultures (> 24 hours) become
more opaquely grey and sometimes
cause the underlying agar to turn
dark.
• Heavily encapsulated strains may be
mucoid.
STREPTOCOCCUS
PNEUMONIAE

• Growth on blood agar

• Alpha-hemolysis
• Susceptible to optochin
• Small, grey, moist
(sometimes mucoidal),
watery colonies with a
surrounding green zone
of alpha-hemolysis.
HAEMOPHILUS
INFLUENZAE

• Growth on chocolate agar

• Large, colorless-to-grey,
opaque colonies on a CAP
• Encapsulated strains
appear more mucoidal
than non-encapsulated
strains, which appear as
smaller compact grey
colonies.
CRYPTOCOCCAL
MENINGITIS

• White mucoid
colonies within
48hours
• Cultures often
positive in
immunosuppressed
patients
POLYMERASE CHAIN
REACTION
• Species-specific real-time PCR assays
• PCR detection of N. meningitidis, H. influenzae, and S.
pneumoniae can be achieved by amplification of several
potential gene targets (8, 35, 53, 60). The following assays have
been developed and validated to be used on DNA extracted
from clinical specimens (typically, blood and CSF) and bacterial
isolates.
• Serogroup/serotype-specific real-time PCR assays
• The capsule gene loci of both N. meningitidis and H. influenzae
have areas that are both unique and conserved within each
serogroup (N. meningitidis) or serotype (H. influenzae) thus
providing gene targets for the development or real-time PCR
assays designed to identify each specific serogroup or serotype.
SEROLOGIC
DIAGNOSTIC

• Crucial diagnostic tool

• Detection of IgM in CSF
• Serum antibody detection is less useful for viruses
with high prevalence rates in the general population.
• For viruses with low prevalence rates, diagnosis with
acute viral infection can be made by documenting.
• Seroconversion between acute phase and
convalescent sera.
• The documentation of synthesis of virus specific
antibodies in CSF is more useful than serum serology
alone.
OTHERS

• CBC ( Complete Blood Count) & DLC ( Differential

Leucocyte Count)
• Liver and Renal Function Test
• ESR ( Erythrocyte Sedimentation Rate)
• C- Reactive Protein
MENINGITIS
NURUL IRYANI BINTI MAZLISHAH
012014100090
CONTENT
Content
ANTIFUNGAL
Learning Objectives ANTIVIRUS
Definition
Causes of meningitis (causal microorganisms)
Antibacterial agents
Antimycobacterial agents
Chemoprophylaxis of meningitis
Summary
Question and answer
References
LEARNING
OBJECTIVES
By the end of this presentation, students should be able to :
• Define meningitis
• State the causal microorganisms
• Prescribe suitable antimicrobial, antimycobacterial agents for
patient with meningitis according to the cause
• State the proper chemoprophylaxis to prevent meningitis
during outbreak
 WHAT IS MENINGITIS?
Definition
• Inflammatory process
involving the leptomeninges
within subarachnoid space
• Caused by infection
• Acute pyogenic, aseptic or
chronic
 COCCI
GRAM
NEGATIVE
BACILLI

AGENT COCCI

GRAM POSITIVE

BACILLI

MYCOBACTERIA
 CAUSAL MICROORGANISMS
Gram negative cocci (aerobic)
Pathogen Drug of first choice Alternative drug
Neisseria meningitidis Penicillin G Chloramphenicol,
ceftrxone, cefotaxime

Gram negative bacilli (aerobic)

Pathogen Drug of first choice Alternative drug
E coli, Klebsiella, Cephalosporin (1G or Quinolone,
Proteus 2G), TMP-SMZ aminoglycoside
CAUSAL MICROORGANISMS
Gram positive cocci (aerobic)

Pathogen Drug of first choice Alternative drug

Streptococcus Penicillin Doxycyclin,
Pneumoniae ceftriaxone,
antipneumococcal
quinolone, macrolide,
linezolid
Staphylococcus aureus Penicillin Cephalosporin (1G),
-MRSA : vancomycin vancomycin
-MRSA : TMP-SMZ,
Linezolid
Gram positive bacilli

Pathogen Drug of first Alternative drug

choice
Listeria sp Ampicillin (± TMP-SMZ
aminoglycoside)
 CAUSAL MICROORGANISMS
Mycobacteria

Pathogen Drug of choice Alternative drug

Mycobacterium Isoniazid + rifampin + Streptomycin,
tuberculosis ethambutol + moxifloxacin,
pyrazinamide amikacin, ethionamide,
linezolid
ANTIMICROBIALS USED FOR
BACTERIAL MENINGITIS
Category Common Drug of first Alternative drug
pathogen choice (DOC)

Neonate Group B ampicillin + Ampicillin +

streptococcus, cephalosporin aminoglycoside,
Escherichia coli, (3G) chloramphenicol,
Listeria meropenem

Child H. Influenza, Ceftriaxone or Chloramphenicol,

pneumococcus, cefotaxime ± meropenem
meningococcus vancomycin

Adult Pneumococcus, Ceftriaxone, Vancomycin +

meninggococcus cefotaxime ceftraixone or
cefotaxime
ANTIMICROBIALS USED FOR
BACTERIAL MENINGITIS
Category Common Drug of first Alternative drug
pathogen choice (DOC)

Neonate Group B ampicillin + Ampicillin +

streptococcus, cephalosporin aminoglycoside,
Escherichia coli, (3G) chloramphenicol,
Listeria meropenem

Child H. Influenza, Ceftriaxone or Chloramphenicol,

pneumococcus, cefotaxime ± meropenem
meningococcus vancomycin

Adult Pneumococcus, Ceftriaxone, Vancomycin +

meninggococcus cefotaxime ceftraixone or
cefotaxime
PENICILLINS

MECHANISM OF ACTION
Bactericidal

• In multiplying/ growing bacteria - Inhibit transpeptidase enzyme

required for the formation of peptidoglycan which is responsible
for the integrity of bacterial cell wall
• In mature bacteria – bind to PBPs (penicillin-binding proteins
which normally prevent autolysis of bacteria) and inhibit them
causing autolysis of bacteria

• Bacterial cell wall has :

• Peptidoglycan : murein or mucopeptide
• Polysaccharide: NAM ( N-acetyl-muramic acid) and NAG (
N-acetyl-glucosamine
Water enters and leads to
lysis of bacterial cell wall
PHARMACOKINETICS
• Usually given by IV or IM route as meningitis is
a medical emergency

• Widely distributed

• Cross BBB when meniges are inflammed

(adequate for meningitis)

• Excreted unchanged in urine by active tubular

secretion

• Probenecid competes with penicillins at tubular

secretion and maintain high levels of penicillins
and also prolong action of penicillins
 BACTERIAL RESISTANCE
TO PENICILLIN
Decrease ability drug penetrate site of action

Altered PBP which has less affinity to Β-lactam.

• Eg: S.pneumoniae
Β-lactamase destroy Β-lactam ring
• Eg : S.aureus, E.coli, H.influenze
 USES
Drug of choice for meningococci, streptococci,
staphylococci

3G cephalosporin + vancomycin + ampicillin :

DOC of meningitis for empirical therapy of bacterial
meningitis.

Duration action :4-6 hours

For penicillin resistant

• Methicillin, Nafcillin, Isoxazolyl penicillin (Cloxacillin)
COMBINATION OF BROAD SPECTRUM
PENICILLINS AND BETALACTAMASE
INHIBITORS

Eg Co- amoxiclav
Amoxicillin + clavulanic acid

DOC for invasive E coli infection

presence of clavulanic acid in Augmentin protects amoxicillin

from degradation by beta-lactamase enzyme

extends the antibacterial spectrum

ADVERSE EFFECTS
Pain at IM site
Hypersensitivity : rash, urticaria,fever, angioedema, serum
sickness, anaphylactic shock ( severe hypotension,
bronchospasm)

Precaution : penicillin skin testing to evaluate penicillin allergy.

Adrenaline injection is kept prepared.
CEPHALOSPORINS
• Β-lactam antibiotic (7-aminocephalosporanic)
• Bactericidal
• Inhibit synthesis of cell wall
• Probenecid prolongs its action

Cross BBB
• 2G : cefuroxime
• 3G : cefotaxime, ceftriaxone
• 4G : cefepime
THIRD GENERATION
CEPHALOSPORINS
• Cefotaxime, ceftriaxone

• Reach high concentration in CSF

• Resistant to B-lactamase enzyme

• Uses : meningitis by meningococci and Haemophilus

influenzae

Spectrum
• Gram positive (↑)
• Gram negative (↑↑↑)
ADVERSE EFFECTS
Hypersensitivity : allergic reaction, rash, rare anaphylactis

GIT disturbance : diarrhea, vomit

Pain at IM, thrombophlebitis if IV

Disulfiram-like reaction with cefoperazone

Severe bleeding due to hypoprothrombinaemia.

ANTIMYCOBACTERI
AL AGENTS
Isoniazid(INH), rifampin, pyrazinamide

RIFAMPIN
MOA : inhibit DNA-dependent RNA polymerase. Blocking
production of RNA
ANTITUBERCULOSIS
AGENTS
First line : isoniazid, rifampin, pyrazinamide

Second line : para-aminosalicylic acid, amikacin, kanamycin

Other : levofloxacin
ANTITUBERCULOSIS
AGENTS
Isoniazid(INH), rifampin, pyrazinamide

RIFAMPIN
bactericidal

MOA : inhibit DNA-dependent RNA polymerase. Blocking

production of RNA
PHARMACOKINETICS
Oral
Adult dose : 600mg every 12 hours for 4 doses.
Rapid GI absorption.
Food reduce absorption.
Metabolized in liver
Excretion
• in bile : and enter enterohepatic recycling.
• In urine
ADVERSE EFFECTS
Hepatitis
Flu-like syndrome : fever, chills, muscle pain
GI disturbance : nausea, vomiting, abdominal discomfort
Skin rash, itching
Flushing
Harmless orange-red urine
DRUG INTERACTIONS
A potent microsomal enzyme inducer

Reduce plasma level of :

• Oral anti-coagulant
• Oral contraceptive
ISONIAZID
MOA : inhibit biosynthesis of mycolic acid, essential
mycobacterial cell

INH : isonicotinic hydrazide (active form)

Readily absorbed from gut
Cross placenta and enters CSF

Uses : bactericidal against M tuberculosis.

ADVERSE EFFECTS

Hepatotoxicity in elderly and chronic alcoholic

Fever, skin rash, arthralgia

Enzyme inhibitor
• Inhibit metabolism phenytoin,
warfarin

Peripheral neuritis
• INH + pyridoxine reduces the risk
 CORTICOSTEROIDS
Reduction of inflammatory effects associated
with mycobacterial killing by the antimicrobial
agents.
Dexamethasone-recommended dose is 60-80
mg/day, which may be tapered gradually
during a span of 6 weeks.
PREVENTION
CHEMOPROPHYLAXIS
Meningococcal polysaccharide vaccine(MPSV4)
• Subcutaneous
• One dose
• For traveler to endemic area, microbiologist
• Booster every 5 years

Meningococcal conjugate vaccine

• IM
• One dose
• For all adolescent, 11-55 years old, military recruit
SUMMARY
Intravenous antimicrobials should be started while waiting
for the culture and sensitivity result
Dexamethasone : reduce mortality in adult with
pneumococcal meningitis + appropriate antimicrobial
QUESTION AND
ANSWER

Which of these drugs are enzyme inducer

a) Rifampin
b) Ceftriaxone
c)Benzylpenicillin
d) isoniazid
QUESTION AND
ANSWER

Which of these drugs are enzyme inducer

a) Rifampin-true
b) Ceftriaxone-false
c)Benzylpenicillin-false
d) isoniazid-false
TRUE OR FALSE
Isoniazid is a second line antituberculosis drug

Ceftriaxone is the DOC of meingitis in adult because pen G

cross BBB poorly

Procainamide prolongs pen G action

Penicillins inhibit transpeptidation reaction.

TRUE OR FALSE
Isoniazid is a second line antitubercular. (False.first line)

Ceftriaxone is the DOC of meingitis in adult because pen G

cross BBB poorly (true)

Procainamide prolongs pen G action (false.probenecid)

Pen G MOA is inhibit transpeptidation reaction.

(true.and inhibit PBP)
REFERENCES
Katzung, B. G., Masters, S. B., & Trevor, A. J. (2012). Basic &
clinical pharmacology. New York: McGraw-Hill Medical.
http://emedicine.medscape.com/article/232915-clinical
http://www.cdc.gov/meningitis/bacterial.html
THANK
YOU
TREATMENT FOR
NON-BACTERIAL
MENINGITIS
NURUL NAJIHA BINTI ZAINUDIN
012014100095
OUTLINES
Antiviral- Acyclovir, Zidovudine
Antifungal- Amphotericin B & Flucytosine
Antiprotozoal- Albendazole, Praziquantel
Supportive therapy
ANTIVIRAL
Treatment of mild cases of viral meningitis
usually includes:
-Bed rest
-Plenty of fluids
-Over- the counter pain medications to help
reduce fever and relieve body aches
ACYCLOVIR
Mechanism of action:
• nucleoside analogue
• It is converted to monophosphate by viral
thymidine kinase
• Then host cell kinase convert
monophosphate to trisphosphate
• Trisphosphate inhibits viral DNA polymerase
and causes premature DNA chain termination
PHARMACOKINETICS

About 20% of an oral dose is

absorbed
Less plasma protein bound
Primarily excreted unchanged in
urine both by glomerular filtration
and tubular secretion
Half life is 2 to 3 hours
Clinical use:
• Herpes Simple Virus
• Varicella Zoster Virus
• Epstein-Barr Virus

Adverse Effect:
• Local irritation: topical application
• Headache, diarrhoea, nausea and vomiting: oral
administration
• Transient renal dysfunction: intravenously with high
doses or dehydrated patient
Zidovudine
O Route: Oral
O Mechanism of action:
O Competitive inhibition of HIV-1 reverse
transcriptase
O Incorporation into growing viral DNA chain causes
premature chain termination due to inhibition of
binding with incoming nucleotide
O Half-life: 1 hour
O Clinical uses: HIV
O Adverse effect:
O Myelosuppresion, macrocytic anemia
O GI intolerance
O Headache, insomnia, anxiety, confusion
ANTIFUNGAL
Amphotericin B

MOA: Amphotericin B associates with

ergosterol, the main component of fungal
cell membrane and forms a
transmembrane channel.
leading to monovalent ion (K+, Na+, H+ and
Cl−) leakage, and leading to fungal cell
death. (leakage of cell membrane).
 PHARMACOKINETICS
Absorption: IV, rarely used orally

Distribution: widely distributed in the body, CSF

penetration poor

Metabolism: about 60% of AMB is metabolized in liver

Excretion: half life is 15days, occurs slowly in both urine

and bile
Uses: Candida albicans,
Cryptococcus neoformans,
Histoplasma capsulatum, Coccidiodes
immits

AE: headache, fever, weight loss,

hypotension, pain at the injection site,
hypokalemia, tachypnea
 Flucytosine

MOA: Narrow spectrum fungistat.

Converted into fluorouracil and further into 5-
fluorouridinetriphosphate interfering with RNA
biosynthesis and building of certain essential
proteins.
Conversion into 5-
fluorodeoxyuridinemonophosphate which
inhibit fungal DNA synthesis.
PHARMACOKINETICS
Absorbed rapidly and almost completely from
GIT
Widely distributed throughout body tissue and
fluids
90% of a dose is excreted unchanged in urine
The half life is 2.5 to 6 hours in patients with
normal renal function.
Uses: Cryptococcus neoformans, Candida
sp
AE: lower toxicity than AMB, GIT
disturbances, done marrow depression
DI: Flucytosine is commonly used with
AMB
Fluconazole
Route: Oral, IV, Topical
Mechanism of action:
• Inhibit fungal cytochrome P450 enzyme 14
alpha-demethylase thus prevent conversion
from lanosterol to ergosterol
• Excellent CNS penetration
Clinical uses:
• Cryptococcal meningitis
• Candida, Cryptococcosis, Coccidiodal
meningitis, Histoplasmosis
Half-life: 25-30 hours
Adverse effect:
• Nausea, vomiting, diarrhea, abdominal
pain
• Headache, dizziness
• Rash
ANTIPROTOZOAN
PHARMACOKINETICS

Administered orally, absorption

increased with fatty meal
Metabolized in the liver to the
active metabolite albendazole
sulfoxide
It enters the brain & excreted with
urine with half life of 8.5 hours
Uses: Neurocysticercosis,
Taeniasis, Ascaris, Hydatid
disease, Strongyloidosis, Filariasis

AE: GIT disturbances, alopecia,

liver damage, bone marrow
depression
Praziquantel

Route: Oral
Half-life: 0.8-1.5 hour
Mechanism of action:
• Increase permeability of trematode and
cestodes cell membrane to calcium, resulting in
paralysis, dislodgement and death
Clinical uses:
• Neurocysticercosis, Taeniasis
• Clonorchiasis
• Schistosomiasis
Adverse effect:
•Rashes, fever
•Nausea and abdominal pain
•Headache, dizziness
•Mental changes, seizures,
intracranial hypertension
SUPPORTIVE
THERAPY
1. Correction of fluid and electrolyte
disturbances
2. Control and maintenance of normal
body temperature
3. Control of convulsions
4. Control of increased intracranial
pressure and cerebral edema
5. Nutritional support
REFERENCES
• Katzung, B. G., Masters, S. B., &
Trevor, A. J. (2012). Basic & clinical
pharmacology. New York: McGraw-
Hill Medical.
• http://emedicine.medscape.com/arti
cle/232915-clinical
• http://www.cdc.gov/meningitis/bacte
rial.html