PATOGENESIS DAN

TINJAUAN KLINIS DEMAM

D I V. I M U N O L O G I D E P T.
MIKROBIOLOGI
P S P D F K U N TA N
DEFINITION

Febrile illness was defined as any illness

with one or more of the following
elements:
axillary temperature of 38.0C
parental report of a temperature of
38.0C measured at home within the
previous 24 hours
parental report that the child felt
hot in the previous 24 hours
(10th revision of the international classification of diseases,
Australian modification codes R50, R50.0, R50.1, R50.9, and R56.0)
 PENGATURAN SUHU TUBUH

Core temperature (suhu tubuh dalam, diukur melalui anus /

mulut )
Skin temperature (diukur melalui ketiak)

studies of healthy individuals 1840 years of age,

- mean oral temperature is 36.8 0.4C (98.2 0.7F),
with low levels at 6 A.M. and higher levels at 46 P.M.
- maximum normal oral temperature is 37.2C (98.9F) at
6 A.M. and 37.7C (99.9F) at 4 P.M
- A.M. temperature of >37.2C (>98.9F) or a P.M.
temperature of >37.7C (>99.9F) would define a fever.
- normal daily temperature variation is typically 0.5C
(0.9F). -- recovering from a febrile illness, 1.0C.
3
 Rectal temperatures are generally 0.4C (0.7F)
higher than oral readings.
The lower oral readings are probably attributable to
mouth breathing, which is a factor in patients with
respiratory infections and rapid breathing.
Lower-esophageal temperatures closely reflect core
temperature.
Tympanic membrane (TM) thermometers measure
radiant heat from the tympanic membrane and
nearby ear canal and display that absolute value
(unadjusted mode) or a value automatically
calculated from the absolute reading on the basis of
nomograms relating the radiant temperature
measured to actual core temperatures obtained in
clinical studies (adjusted mode). These
measurements, although convenient, may be more
variable than directly determined oral or rectal
values.
Studies in adults show that readings are lower with
unadjusted-mode than with adjusted-mode TM
 KONTROL SUHU
TUBUH

Keseimbang
an
antara Heat
Produksi Loss
Panas Heat
Productio
dan n
Kehilangan
panas 5
 PRODUKSI
PANAS
Metabolic rate of the body:
Basal rate of metabolism (BMR)

metabolisme utk mempertahankan

kehidupan saja
Extra rate of metabolism:
- muscle contraction
- hormonal effects
- sympathetic effects
(mis: makan bnyk protein
- chemical activity
badan jadi lebih panas)

6
 KEHILANGAN
PANAS
Heat conducted: body core skin
Heat transferred: skin surroundings
- Insulator system of the body
- Blood flow: body core skin
- Control blood flow by sympathetic

NB:
dehidrasi evaporasi << core heat tdk bs
ke skin)

7
 KEHILANGAN
PANAS
Heat transferred: skin surroundings

- Radiation(scr langsung ke lingkungan)

- Conduction (melalui sentuhan)

- Convection (melalui aliran udara : fan, AC

air : kompres, mandi)

- Evaporation sweat secretion

(pd binatang, eg : anjing menjulurkan

- Panting
lidah), hal ini tdk mempengaruhi jumlah
udara respirasi

8
 PENGATURAN SUHU
TUBUH

Reflex: nervous feedback mechanism

Regulation center: hypothalamus
Set-Point
Hypothalamic-preoptic: heat-sensitive &
cold-sensitive neuron
Receptors: in the skin & deep body
tissues
Behavioral control
Local skin temperature reflex 9
 PENGATURAN SUHU
TUBUH
Temperature-increasing mechanism
Temperature-decreasing mechanism

Neurons in both the preoptic anterior hypothalamus and the

posterior hypothalamus receive two kinds of signals:
- one from peripheral nerves that transmit information from
warmth/cold receptors in the skin
- the other from the temperature of the blood bathing the
region.
These two types of signals are integrated by the
thermoregulatory center of the hypothalamus to maintain
normal temperature. In a neutral temperature environment, the
metabolic rate of humans produces more heat than is
necessary to maintain the core body temperature at 37C.
10
 PENGATURAN SUHU
TUBUH
Temperature-increasing mechanism

- Vasoconstriction (mengurangi heat loss, kulit

jd pucat)

- Piloerection (bulu berdiri : udara terperangkap

diantara bulu, meningkatkan insulator)

- Increase in heat production:

> shivering (menggigil) kontraksi otot
menghasilkan panas
> sympathetic excitation
> thyroxin secretion 11
 PENGATURAN SUHU
TUBUH

Temperature-decreasing mechanism:

- Vasodilatation inhibition of
sympathetic center
(wajah jd merah)
- Sweating
- Decrease in heat production
> strongly inhibited the mechanism causes
excess heat production
12
FEVER VERSUS HYPERTHERMIA
Fever
Fever is an elevation of body temperature that exceeds
the normal daily variation and occurs in conjunction
with an increase in the hypothalamic set point (e.g.,
from 37C to 39C).
Once the hypothalamic set point is raised, neurons in
the vasomotor center are activated and
vasoconstriction commences. The individual first
notices vasoconstriction in the hands and feet.
Shunting of blood away from the periphery to the
internal organs essentially decreases heat loss from
the skin, and the person feels cold.
For most fevers, body temperature increases by 12C.
Shivering, which increases heat production from the
muscles, may begin at this time; however, shivering
is not required if heat conservation mechanisms raise
blood temperature sufficiently.
Nonshivering heat production from the liver also
contributes to increasing core temperature. In
The processes of heat conservation (vasoconstriction)
and heat production (shivering and increased
nonshivering thermogenesis) continue until the
temperature of the blood bathing the hypothalamic
neurons matches the new thermostat setting.
Once that point is reached, the hypothalamus maintains
the temperature at the febrile level by the same
mechanisms of heat balance that function in the
afebrile state.
When the hypothalamic set point is again reset
downward (in response to either a reduction in the
concentration of pyrogens or the use of antipyretics),
the processes of heat loss through vasodilation and
sweating are initiated.
Loss of heat by sweating and vasodilation continues
until the blood temperature at the hypothalamic level
matches the lower setting. Behavioral changes (e.g.,
 HYPERPYREXIA
A fever of >41.5C (>106.7F) is called hyperpyrexia.
This extraordinarily high fever can develop in patients
with severe infections but most commonly occurs in
patients with central nervous system (CNS)
hemorrhages.

In rare cases, the hypothalamic set point is elevated as a

result of local trauma, hemorrhage, tumor, or intrinsic
hypothalamic malfunction. The term hypothalamic
fever is sometimes used to describe elevated
temperature caused by abnormal hypothalamic
function. However, most patients with hypothalamic
damage have subnormal, not supranormal, body
temperatures.
Hyperthermia
Although most patients with elevated body temperature
have fever, there are circumstances in which elevated
temperature represents not fever but hyperthermia
Hyperthermia is characterized by an uncontrolled increase
in body temperature that exceeds the body's ability to
lose heat. The setting of the hypothalamic
thermoregulatory center is unchanged.
In contrast to fever in infections, hyperthermia does not
involve pyrogenic molecules (see "Pyrogens," below).
Exogenous heat exposure and endogenous heat
production are two mechanisms by which hyperthermia
can result in dangerously high internal temperatures.
Excessive heat production can easily cause hyperthermia
despite physiologic and behavioral control of body
temperature. For example, work or exercise in hot
environments can produce heat faster than peripheral
mechanisms can lose it.
Causes of Hyperthermia Syndromes
Heat Stroke
Exertional: Exercise in higher-than-normal heat and/or humidity
Nonexertional: Anticholinergics, including antihistamines;
antiparkinsonian drugs; diuretics; phenothiazines
Drug-Induced Hyperthermia
Amphetamines, cocaine, phencyclidine (PCP),
methylenedioxymethamphetamine (MDMA; "ecstasy"), lysergic acid
diethylamide (LSD), salicylates, lithium, anticholinergics,
sympathomimetics
Neuroleptic Malignant Syndrome
Phenothiazines; butyrophenones, including haloperidol and
bromperidol; fluoxetine; loxapine; tricyclic dibenzodiazepines;
metoclopramide; domperidone; thiothixene; molindone; withdrawal of
dopaminergic agents
Serotonin Syndrome
Selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase
inhibitors (MAOIs), tricyclic antidepressants
Malignant Hyperthermia
Inhalational anesthetics, succinylcholine
Endocrinopathy
Thyrotoxicosis, pheochromocytoma
Heat stroke in association with a warm environment may be categorized as
exertional or nonexertional.
Drug-induced hyperthermia has become increasingly common as a result of the
increased use of prescription psychotropic drugs and illicit drugs.
Malignant hyperthermia occurs in individuals with an inherited abnormality of
skeletal-muscle sarcoplasmic reticulum that causes a rapid increase in
intracellular calcium levels in response to halothane and other inhalational
anesthetics or to succinylcholine.

It is important to distinguish between fever and hyperthermia since hyperthermia

can be rapidly fatal and characteristically does not respond to antipyretics. I
n an emergency situation, however, making this distinction can be difficult. For
example, in systemic sepsis, fever (hyperpyrexia) can be rapid in onset, and
temperatures can exceed 40.5C.
Hyperthermia is often diagnosed on the basis of the events immediately preceding
the elevation of core temperaturee.g., heat exposure or treatment with drugs
that interfere with thermoregulation. In patients with heat stroke syndromes
and in those taking drugs that block sweating, the skin is hot but dry, whereas
in fever the skin can be cold as a consequence of vasoconstriction. Antipyretics
do not reduce the elevated temperature in hyperthermia, whereas in fever
and even in hyperpyrexiaadequate doses of either aspirin or acetaminophen
usually result in some decrease in body temperature.
 PATHOGENESIS OF FEVER
Pyrogens
The term pyrogen is used to describe any substance that causes fever.
Exogenous pyrogens are derived from outside the patient; most are microbial products, microbial
toxins, or whole microorganisms. The classic example of an exogenous pyrogen is the
lipopolysaccharide (endotoxin) produced by all gram-negative bacteria. Pyrogenic products of
gram-positive organisms include the enterotoxins of Staphylococcus aureus and the group A and
B streptococcal toxins, also called superantigens. One staphylococcal toxin of clinical importance
is that associated with isolates of S. aureus from patients with toxic shock syndrome. These
products of staphylococci and streptococci cause fever in experimental animals when injected
intravenously at concentrations of 110 g/kg. Endotoxin is a highly pyrogenic molecule in
humans: when injected intravenously into volunteers, a dose of 23 ng/kg produces fever,
leukocytosis, acute-phase proteins, and generalized symptoms of malaise.
Pyrogenic Cytokines
Cytokines are small proteins (molecular mass, 10,00020,000 Da) that regulate immune,
inflammatory, and hematopoietic processes. For example, the elevated leukocytosis seen in
several infections with an absolute neutrophilia is the result of the cytokines interleukin (IL) 1
and IL-6. Some cytokines also cause fever; formerly referred to as endogenous pyrogens, they
are now called pyrogenic cytokines. The pyrogenic cytokines include IL-1, IL-6, tumor necrosis
factor (TNF), ciliary neurotropic factor (CNTF), and interferon (IFN) . (IL-18, a member of the IL-1
family, does not appear to be a pyrogenic cytokine.) Other pyrogenic cytokines probably exist.
Each cytokine is encoded by a separate gene, and each pyrogenic cytokine has been shown to
cause fever in laboratory animals and in humans. When injected into humans, IL-1 and TNF
produce fever at low doses (10100 ng/kg); in contrast, for IL 6, a dose of 110 g/kg is required
for fever production.
A wide spectrum of bacterial and fungal products induce the synthesis and release of pyrogenic
cytokines, as do viruses. However, fever can be a manifestation of disease in the absence of
microbial infection. For example, inflammatory processes, trauma, tissue necrosis, or antigen-
antibody complexes can induce the production of IL-1, TNF, and/or IL-6, whichindividually or in
combinationtrigger the hypothalamus to raise the set point to febrile levels.
Elevation of the Hypothalamic Set Point by Cytokines

During fever, levels of prostaglandin E2 (PGE2) are elevated in

hypothalamic tissue and the third cerebral ventricle. The
concentrations of PGE2 are highest near the circumventricular
vascular organs (organum vasculosum of lamina terminalis)
networks of enlarged capillaries surrounding the hypothalamic
regulatory centers. Destruction of these organs reduces the ability of
pyrogens to produce fever. Most studies in animals have failed to
show, however, that pyrogenic cytokines pass from the circulation
into the brain itself. Thus, it appears that both exogenous and
endogenous pyrogens interact with the endothelium of these
capillaries and that this interaction is the first step in initiating fever
i.e., in raising the set point to febrile levels.
The key events in the production of fever are illustrated in Fig. 17-1. As
has been mentioned, several cell types can produce pyrogenic
cytokines. Pyrogenic cytokines such as IL-1, IL-6, and TNF are
released from the cells and enter the systemic circulation. Although
the systemic effects of these circulating cytokines lead to fever by
inducing the synthesis of PGE2, they also induce PGE2 in peripheral
tissues. The increase in PGE2 in the periphery accounts for the
nonspecific myalgias and arthralgias that often accompany fever. It is
thought that some systemic PGE2 escapes destruction by the lung and
gains access to the hypothalamus via the internal carotid. However, it
PATHOPHYSIOLOGY OF FEVER

Pathophysiology: 3 causes
Raising of hypothalamic set point in CNS
Infection, collagen vascular disease,
malignancies
lowered by antipyretic medication and
removing heat
Heat production exceeding heat loss
salicylate overdose, hyperthyroidism,
environmental heat
Defective heat loss
ectodermal dysplasia, heat stroke, poisoning
with certain drugs
PATHOPHYSIOLOGY OF
FEVER
There are four receptors for PGE2, and each signals the cell in different ways. Of the
four receptors, the third (EP-3) is essential for fever: when the gene for this receptor
is deleted in mice, no fever follows the injection of IL-1 or endotoxin. Deletion of the
other PGE2 receptor genes leaves the fever mechanism intact. Although PGE2 is
essential for fever, it is not a neurotransmitter. Rather, the release of PGE2 from the
brain side of the hypothalamic endothelium triggers the PGE2 receptor on glial cells,
and this stimulation results in the rapid release of cyclic adenosine 5'-
monophosphate (cyclic AMP), which is a neurotransmitter. As shown in Fig. 17-1, the
release of cyclic AMP from the glial cells activates neuronal endings from the
thermoregulatory center that extend into the area. The elevation of cyclic AMP is
thought to account for changes in the hypothalamic set point either directly or
indirectly (by inducing the release of neurotransmitters). Distinct receptors for
microbial products are located on the hypothalamic endothelium. These receptors
are called Toll-like receptors and are similar in many ways to IL-1 receptors. The
direct activation of Toll-like receptors also results in PGE2 production and fever.
Production of Cytokines in the CNS
Several viral diseases produce active infection in the brain. Glial and possibly neuronal
cells synthesize IL-1, TNF, and IL-6. CNTF is also synthesized by neural as well as
neuronal cells. What role in the production of fever is played by these cytokines
produced in the brain itself? In experimental animals, the concentrations of cytokine
required to cause fever are several orders of magnitude lower with direct injection
into the brain than with IV injection. Therefore, CNS production of these cytokines
apparently can raise the hypothalamic set point, bypassing the circumventricular
organs involved in fever caused by circulating cytokines. CNS cytokines may account
for the hyperpyrexia of CNS hemorrhage, trauma, or infection.
DIAGNOSIS

History
Physical examination
Laboratory
CBC
Acute phase reactant : ESR, CRP, Procalcitonin
Blood culture
Urinalysis and Urin culture
Serologic
Lumbal puncture : CSF study
Imaging : Chest x ray, ultrasound, CT-scan, MRI
HISTORY

1. Age :

2. Duration of fever :
- Fever lasting for 4-7 days is rarely due to self
limiting viral illness and needs investigation.
- Fever lasting for 2 weeks indicates serious
underlying problem and needs thorough investigation.

3. Chills and rigors: both are non specific and suggest no

definite etiology.

4. Pattern of fever: The wide use of the antipyretics

modifies the natural pattern of fever. Nausea may indicate
hepatic disease. Persistence of headache and vomiting
may indicate meningitis.
 HISTORY
5. Contact with similar diseases
. 6. Past history of similar illness: Recurrent viral infections are
common in children especially in the first year of school. Children
between 2 months to 6 years of age are also susceptible to recurrent
viral infections. Malaria may often recur, as the therapy is merely
suppressive.
7. Drugs used in the treatment and its responseHence theinter
febrilestate helps in the evaluation of the probable cause of fever
(Fig.1). Patterns of fever have limited value in predicting the
etiology of fever.
8.Progress of fever: Fever due to viral infection peaks over a day
or two and gradually declines in 3-4 days. Bacterial fever worsens if
left untreated. Malarial fever develops suddenly and declines swiftly.

Clinical approach to a child with fever | Medindia

http://www.medindia.net/education/familymedicine/f
everinchildren-clinicalapproach.htm#ixzz2wn1zPQyM
 HISTORY
9. Accompanying symptoms:
- Specific symptoms help in localising the site of
infection such as
- Non specific symptoms include bodyache, headache,
anorexia, vomiting and irritability.
- Persistence of anorexia and Therapeutic response to
an antibiotic is very difficulty to assess accurately.
Natural remission of a viral fever may be interpreted as
response to an antibiotic.
- Typically, fever due to bacterial infection responds to
antibiotic in 2-3 days.
- Typhoid fever takes longer duration to normalize.

10. Immunization:Vaccine preventable diseases are rare

in immunized children.

Clinical approach to a child with fever | Medindia http://www.medindia.net/education/familymedicine/feverinchildren-

PHYSICAL EXAMINATION

1. Assess seriousness:Presence of the following signs

suggests the possibility of serious underlying diseases: a)
Respiratory distress b) Drowsiness / meningeal signs c)
Signs of impending shock d) Purpuric spots e) Faucial
membrane f) Abdominal guarding / rigidity
2. General examination:
i) General appearance:Toxic/ill look indicates serious illness.
Irritability or discomfort may either be due to pain or respiratory
distress. A comfortable child indicates that a benign illness is
likely.

ii) Body temperature: Must be quickly judged by merely touching

the skin over the central and peripheral parts of the body.
Differential body temperature: warm chest/abdomen and cool
periphery-indicates severe illness.
 PHYSICAL EXAMINATION

iii) Pulse rate: With every degree Fahrenheit rise in

the fever, pulse rate goes up by 10 beats/min.
Disproportionate increase in the pulse rate may
suggest early sepsis or primary cardiac disease.

iv) Respiratory rate: Normal ratio of pulse and

respiration in health is 4:1. The ratio is increased
in primary cardiac disease and decreased in
respiratory pathology.
v) Skin rash
vi) Lymphadenopathy
vii) ENT examination
 PHYSICAL EXAMINATION
Red flag of serious infection

Cyanosis
Rapid breathing
Poor perfusion
Petechial rashes
High fever 40 o C
Parental concern
Clinician instinc
No single clinical feature has rule-out value but some
combinations can be used to exclude the possibility of
serious infection

Lancet.2010 Mar 6;375(9717):834-45.

CBC
Measuring WBC count is less useful for ruling in serious
infection and not useful for ruling out serious infection.
Low risk
WBC count < 15,000 (15 109per L)
Bandemia < (1.5 109per L).31
Predictive of SBI sensitivity of 69 % and specificity of 79
%.

Pediatrics. 1994;94:3906.
Pediatr Clin North Am. 1999;46:1073109.
CRP

Quantitative CRP concentration is a valuable

laboratory test in the evaluation of febrile
young children who are at risk for occult
bacteremia and SBI, with a better predictive
value than the WBC or ANC.
Pediatrics.2001 Dec;108(6):1275-9.

CRP provides moderate and independent

information for both ruling in and ruling out
serious bacterial infection in children with fever at
first presentation. Poor sensitivity means that CRP
cannot be used to exclude all bacterial infection.

J Pediatr.2008 Oct;153(4):570-4.
CRP

CRP increas as a response to

inflamatory reaction
CRP concentrations generally
do not increase until 12
hours after the onset of fever
and can rise in both viral and
bacterial infections .
J Pediatr. 1988;113(4):641.
URINALYSIS AND URINE CULTURE

Who needs a urinalysis and urine culture?

Circumcised males < 6 months
Uncircumcised males < 1 year
Females < 2 years
Immunocompromised patients
Patients with history of UTI/pyelonephritis
Non-toxic febrile children older than 3 months of age
who have no obvious source of infection.

http://www0.health.nsw.gov.au/policies/pd/2010/pdf/PD2010_063.pdf
URINALYSIS

Urethral catheterization and

suprapubic aspiration are
preferred methods for
obtaining urine specimens
because of the high rates of
contamination seen with
bagged specimens.
Pediatrics 2000;105(1 pt 1):141
Ann Emerg Med. 2003;42:53045.
STOOL

Most studies of febrile children

did not require evaluation of
stool.
The presence of 5 WBCs/hpf
was predictive
ofSalmonellainfection,
including bacteremia in
patients with diarrhea.
Pediatrics. 1994;94:3906
BLOOD CULTURE

Indicated to proof bacteremia .

To identify the type of bacteria

in the blood or other source
of infection.
LUMBAR PUNCTURE

Lumbar puncture should be

considered in a young infant,
toxic child, irritable child or a
child with complex febrile
convulsions especially if the
child is already on antibiotics
CHEST X RAY

Chest x-ray is most useful if

the child has signs of
respiratory illness such as
cough, tachypnoea, dullness
or crackles. If there are no
respiratory signs perform
other investigations before
the CXR.
DIFFERENTIAL DIAGNOSIS

Fever without localizing sign

Fever with localizing sign
Fever with rash
Fever lasting longer than 7
days
Fever lasting longer than 14
days (Prolonged fever)
Fever of Unknown origin
FEVER WITHOUT LOCALIZING SIGN

Malaria
Septicemia
Typhoid
Urinary tract infection
Fever associated with HIV

ICHRC . http://www.ichrc.org/chapter-612-fever-
lasting-longer-7-days
FEVER WITH LOCALIZING SIGN
Meningitis Skin and soft tissue
Otitis media infection
Pneumonia
Mastoiditisa
Viral Upper
Osteomyelitis Respiratory
Septicemia Infection
Acute Rheumatic Retropharyngeal
fever abcess
Skin and soft Sinusitis
tissue infection Hepatitis

ICHRC . http://www.ichrc.org/chapter-612-fever-
FEVER WITH RASH

Measles
Viral infection
Typhus
Relapsing fever
Dengue hemorrhagic fever
http://www.ichrc.org/chapter-612-fever-lasting-
longer-7-days
FEVER LASTING LONGER THAN 7 DAYS

Abcess
Salmonella infection (non typhoidal )
Infective endocarditis
Rheumatic fever
Miliary TB
Brucellosis
Borreliosis

http://www.ichrc.org/chapter-612-fever-lasting-
longer-7-days
FEVER LASTING LONGER THAN 14 DAYS

Kawasaki diseases
Tuberculosis
HIV
Oncologic diseases
TREATMENT

Antipyretic
Antibiotics
Cold water sponging
Water
Herbal
ANTIPYRETICS
BENEFITS OF FEVER

The hypothalamus will not allow the

temp to rise above 41.5C(107F).
WBCs work best and kill the most
bacteria at 38-40C(100.4-104F).
Neutrophils make more superoxide
anion, and there is more and
increased activity of interferon.
Coxsackie and polio virus
replication is directly inhibited.
 BENEFITS OF FEVER

Protective role in the immune

system
Inhibition of growth and replication of
microorganisms
Aids in bodys acute phase reaction
Enhanced immunologic function of wbcs
lymphocyte response to mitogens
bactericidal activity of neutrophils
production of interferon
Promotion of monocyte maturation into macrophages
Promotion of lymphocyte activation and antibody production
Decreased availability of free iron for bacterial replication
FEVER PHOBIA

Term coined in early 1980s by BD Schmitt, M.D.

Primary fears
Brain damage
Coma
Seizures
Blindness
Death
Other contributors
Technology
Pharmaceuticals
ARGUMENTS AGAINST ANTIPYRESIS

Fever is not an illness

Most fevers are short-lived and benign
Fever may protect the host
Degree of fever does not correlate with severity of illness
fever may obscure diagnostic or prognostic signs
No evidence that children with fever are at risk of adverse
outcomes such as brain damage
Adverse effects of antipyretics outweigh benefits
ANTIPYRETICS

Whenever possible, oral

administration of
paracetamol is preferable
to rectal administration.
Dosage based on weight
than age
ACETAMINOPHEN

Acetaminophen in a dosage of 10 - 15 mg/ kg BW

every 4-6 hours to treat fever in children is safe
and effective. It is estimated that 80 % of
children will have a decrease in temperature
within the first 30 to 60 minutes after
acetaminophen has been administered. There
has been no consistent evidence that increasing
the initial dose of acetaminophen orally or
rectally improves effectiveness.

Am Fam Physician.2012Mar1;85(5):518-519
WHICH PREPARATION?

The syrup more effective

(maximum fall of temperature
1.58 C) than suppository
(1.24 C) in reducing fever.
Eur J Clin Pharmacol. 1977 Aug 17;12(1):77-80.
IBUPROFEN

is not recommended in febrile children with chickenpox or

dehydration. Clin Ther.2009 Aug;31(8):1826-43.

Ibuprofen in a dosage of 10 mg / kg every 6-8 hours is as

effective as acetaminophen, and may have a longer effect on
lowering body temperature. Evidence has not shown any
differences in safety between ibuprofen and acetaminophen
in children six months to 12 years of age with fever. Children
with a high fever who are older than six years do not respond
as effectively to either medication. The primary determinants
of the effectiveness of therapy may be the age of the child
and fever grade, rather than the specific medication used.

Am Fam Physician.2012Mar1;85(5):518-519.
ACETAMINOPHEN AND IBUPROFEN
COMBINATION

Alternating and combination

antipyretic therapy more
effective than monotherapy alone.
However, the evidence for
improvements in measures of
child discomfort remains
inconclusive.

Arch Pediatr Adolesc Med. 2006 Feb;160(2):197-202.

BMJ 2008;337:a1302
Clin Ther. 2010 Dec;32(14):2433-40.
Cochrane Database Syst Rev.2013 Oct 30;10:CD009572.
DIPYRONE

After 4 to 6 hours, mean temperature in

the dipyrone group was significantly
lower than the other groups,
demonstrating longer temperature
normalization with dipyrone. All three
drugs showed comparable tolerability
profiles. Clin Pediatr (Phila).2001
Jun;40(6):313-24.

Adverse reaction ; agranulocytosis,

Contraindication : bleeding disorder
http://www.drugsupdate.com/generic/view/809/Dipyrone
DIPYRONE

it is banned in
developed countries
because of severe
side effects.
J Pediatr Hematol Oncol.2014
Jan;36(1):e46-8.
 TEPID SPONGING

Effective only during the 1st 30

minutes.
More effective if combined with
antipyretic

J Family Med Prim Care. 2013 Apr-Jun; 2(2): 153158.

Ann Trop Paediatr. 1997 Sep;17(3):283-8.
Clin Pediatr (Phila). 1994 Apr;33(4):227-31.
ANTIBIOTIC
Antibiotics are used to treat occult
bacterial infection. Empiric antimicrobial
therapy must be comprehensive and
should cover all likely pathogens for the
patient's age range and in the clinical
setting. Whenever feasible, select
antibiotics based upon blood culture
sensitivity.

http://emedicine.medscape.com/article/1834870-medication
 ANTIBIOTIC

Selecting and initiating

antibiotic regimen

Obtaining an Accurate Infectious Disease Diagnosis

Timing of Initiation of Antimicrobial Therapy
Empiric vs Definitive Antimicrobial Therapy
Interpretation of Antimicrobial Susceptibility Testing
Results
Bactericidal vs Bacteriostatic Therapy
 ANTIBIOTIC

Use of Antimicrobial Combinations

Host Factors to Be Considered in Selection of Antimicrobial Agents
Oral vs Intravenous Therapy
Pharmacodynamic Characteristics
Selection of Antimicrobial Agents for Outpatient Parenteral
Antimicrobial Therapy
Use of Therapeutic Drug Monitoring

Mayo Clin Proc. Feb 2011; 86(2): 156167.

Thank you

Thank you