ASSESSMENT OF THE CHILD WITH DIARRHEA

A child with diarrhea should be assessed for dehydration, bloody diarrhea, persistent diarrhea,
malnutrition and serious non-intestinal infections, so that an appropriate treatment plan can be developed
and implemented without delay. The information obtained when assessing the child should be recorded on a
suitable form.

HISTORY
 Presence of blood in the stool
 Duration of diarrhea
 Number of watery stools per day
o Number of episodes of vomiting
 Presence of fever, cough, or other important problems (e.g. convulsions, recent measles)
o Pre-illness feeding practices
o Type and amount of fluids (including breastmilk) and food taken during the illness
o Drugs or other remedies taken
o Immunization history

PHYSICAL EXAMINATION
Signs and symptoms of dehydration:
• General condition: is the child alert; restless or irritable; lethargic or unconscious?
• Are the eyes normal or sunken?
• When water or ORS solution is offered to drink, is it taken normally or refused, taken eagerly, or is
the child unable to drink owing to lethargy or coma?

Assess:
• Skin turgor
When the skin over the abdomen is pinched and released, does it flatten immediately, slowly,
or very slowly (more than 2 seconds)?

Signs of other important problems.

• Does the child's stool contain red blood?
• Is the child malnourished?
o Remove all upper body clothing to observe the shoulders, arms, buttocks and thighs, for
evidence of marked muscle wasting (marasmus). Look also for edema of the feet; if this is
present with muscle wasting, the child is severely malnourished. If possible, assess the
child's weight-for-age, using a growth chart, or weight-for-length. Alternatively, measure
the mid-arm circumference.
• Is the child coughing? If so, count the respiratory rate to determine whether breathing is abnormally
rapid and look for chest indrawing

Take the child's temperature:

• Fever may be caused by severe dehydration, or by a non-intestinal infection such as malaria or
pneumonia.

Determine the degree of dehydration:

Clinical description:

Infection of the large intestine by Entamoeba histolytica may result in an illness of variable severity
ranging from mild, chronic diarrhea to fulminant dysentery. Infection also may be asymptomatic. Extra-
intestinal infection also can occur (e.g., hepatic abscess).

Laboratory criteria for diagnosis:

Confirmed Case
Laboratory confirmation of infection with or without clinical illness:
Clinical illness varies from mild abdominal discomfort with diarrhea (+/- blood, mucus) alternating
with periods of constipation and/or remission to amoebic dysentery (fever, chills, bloody/mucoid
diarrhea).

• Microscopic demonstration of trophozoites or cysts in fecal specimens, smears of aspirates or

scrapings obtained by proctoscopy, or aspirates of abscess or sections of tissue
OR
• Positive stool antigen detection test
OR
• Positive serology
Antibody response in amebiasis is only seen when tissue invasion has occurred and may represent
past or present disease.
DRUG CLASS: LUMINAL AGENTS

EFFICACY SAFETY SUITABILITY COST TOTAL

METRONIDAZOLE +++ ++ ++++ ++++ 13

TINIDAZOLE ++++ +++ + + 9

ORNIDAZOLE ++++ +++ ++ ++ 11

BASES FOR EFFICACY

RATIONALE

METRONIDAZOLE Pharmacodynamics
+++  Mechanism of action: Metronidazole undergoes a reductive
bioactivation of its nitro group by ferredoxin (present in anaerobic
parasites) to form reactive cytotoxic products. Ferredoxins are small
Fe–S proteins that have a sufficiently negative redox potential to
donate electrons to metronidazole. The single electron transfer forms a
highly reactive nitro radical anion that kills susceptible organisms by
radical-mediated mechanisms that target DNA and possibly other vital
biomolecules.
 Metronidazole is an anti-infectious drug belonging to the
pharmacotherapeutic group of nitroimidazole derivatives, which have
effect mainly on strict anaerobes. Therefore its pharmacodynamics
actions are not relevant to toxicity in man.

Pharmacokinetics

 Preparations of metronidazole are available for oral, intravenous,

intravaginal, and topical administration. The drug usually is absorbed
completely and promptly after oral intake, reaching concentrations in
plasma of 8-13 μg/mL within 0.25-4 hours after a single 500-mg dose.
Repeated doses every 6-8 hours result in some accumulation of the
drug; systemic clearance exhibits dose dependence. Elimination of the
drugs requires hepatic metabolism. The t1/2 of metronidazole in
plasma is ~8 hours; its volume of distribution approximates total body
water. Less than 20% of the drug is bound to plasma proteins. With the
exception of the placenta, metronidazole penetrates well into body
tissues and fluids, including vaginal secretions, seminal fluid, saliva,
breast milk, and CSF.
Clinical Use

 For the treatment of intestinal amebiasis and amebic liver abscess

caused by E. histolytica.

BASES FOR EFFICACY

RATIONALE

TINIDAZOLE Pharmacodynamics
++++  Mechanism of action: Tinidazole is a prodrug and antiprotozoal agent.
The nitro group of tinidazole is reduced by a ferredoxin-mediated
electron transport system. The free nitro radical generated as a result
of this reduction is believed to be responsible for the antiprotozoal
activity. It is suggested that the toxic free radicals covalently bind to
DNA, causing DNA damage and leading to cell death.
 Tinidazole is active against both protozoa and obligate anaerobic
bacteria. The mode of action of Tinidazole against anaerobic bacteria
and protozoa involves penetration of the drug into the cell of the
micro-organism and subsequent damage of DNA strands or inhibition
of their synthesis.

Pharmacokinetics

 The half-life of tinidazole is 12–14 h. Tinidazole is widely distributed in

all body tissues and also crosses the blood brain barrier, obtaining
clinically effective concentrations in all tissues. The apparent volume
of distribution is about 50 litres. About 12% of plasma tinidazole is
bound to plasma protein. Tinidazole is excreted by the liver and the
kidneys. Tinidazole is excreted in the urine mainly as unchanged drug
(approximately 20-25% of the administered dose). Approximately
12% of the drug is excreted in the feces.

Clinical Use

 Tinidazole is indicated for the treatment of intestinal amebiasis and

amebic liver abscess caused by Entamoeba histolytica

BASES FOR EFFICACY

RATIONALE

ORNIDAZOLE Pharmacodynamics
++++  Mechanism of action: Ornidazole is a antiprotozoal drug. It is
converted to reduction products that interact with DNA to cause
destruction of helical DNA structure and strand leading to a protein
synthesis inhibition and cell death in a susceptible organism.

Pharmacokinetics

 The half-life of ornidazole is 12–14 h. Ornidazole is widely distributed

in all body tissues and fluids, CSF. About 15% of plasma ornidazole is
bound to plasma protein. Ornidazole is metabolized in the liver.
Ornidazole is excreted in the urine and feces.
Clinical Use

 Ornidazole is indicated for the treatment of intestinal amebiasis and

amebic liver abscess caused by Entamoeba histolytica

BASES FOR SAFETY

SIDE EFFECTS
METRONIDAZOLE Abdominal Pain (64.8%)
Loss of appetite (44.4%)
++ Nausea (42.6%)
Anal Itching (42.6%)
Headache (38.9%)

Infrequent adverse effects include:

Vomiting, Diarrhea, Metallic taste, Dry mouth, Insomnia, Weakness, Dizziness,
Thrush, Rash, Dysuria, Dark urine, Neutropenia

The most serious side effects reported were convulsive seizures,

encephalopathy, aseptic meningitis, and optic and peripheral neuropathy
(characterized by numbness or paresthesia of an extremity).

BASES FOR SAFETY

SIDE EFFECTS

TINIDAZOLE Tinidazole has a similar adverse effect profile to Metronidazole, but may be
better tolerated.
+++

Bitter Taste (17.5%)

Abdominal Pain (3.2%)
Headache (1.6%)
Rash (1.6%)
Infrequent adverse effects include:
Loss of appetite, Flatulence, Diarrhea, Nausea, Dry mouth, Vomiting, Weakness

BASES FOR SAFETY

SIDE EFFECTS

ORNIDAZOLE Nausea (5.4%)

Diziness (3.6%)
++ Headache (1.8%)

BASES FOR SUITABILITY

METRONIDAZOLE Contraindications
++++  Caution in patient with active or chronic severe peripheral or CNS
diseases. If administered for >10 days, haematological tests are
recommended, monitor patient for symptoms of peripheral or
central neuropathy

Interaction

 There are no food or drug interactions with the current status of

 the patient

Convenience/Dosage Forms

 Oral/Oral suspension - 30-40mg/kg/day in 3 divided dose; Tab -

swallow whole, do not chew/crush; Suspension – should not be
taken 1hr before meals
 Available locally

BASES FOR SUITABILITY

TINIDAZOLE Contraindications
+  In patients with a previous history of hypersensitivity to tinidazole
or other nitroimidazole derivatives. Reported reactions have
ranged in severity from urticaria to Stevens-Johnson syndrome. It is
contraindicated in blood dyscrasias and active neurological
diseases.
Interaction

 Tinidazole may cause live bacterial vaccines to not work as well. Do

not have any immunizations/vaccinations while using medication
unless your doctor tells you to.

Convenience/Dosage Forms

 Oral – 45mg/kg PO qd x 3 days; Max: 2/g dose; Give with food; tabs
may be crushed
 Not available in the Philippines
BASES FOR SUITABILITY

ORNIDAZOLE Contraindications
++  Hypersensitivity to ornidazole or to other nitroimidazole
derivatives.

Interactions

 There are no food or drug interactions with the current status of

the patient

Convenience/Dosage Forms

 Oral – 25mg/kg as a single daily dose for 5-10 days

 Not available in the Philippines

BASES FOR COST

METRONIDAZOLE Recommended Dosage:

++++ 30-40mg/kg/d TID for 7 days
Weight: 15kg
 Preparation: 125mg/5mL suspension, 60mL
Price Php 94.00
15 x 30 x 5 = 18mL TID for 7 days
125
18 x 7 = 2.1; approx. 3 bottles
60
3 bottles x Php94.00 = Php282.00
(Flagyl)

BASES FOR COST

TINIDAZOLE Recommended Dosage:

+ 45mg/kg PO qd x 3 days
Weight: 15kg
Preparation: 500mg
Price Php90.30/tablet
15 x 45 = 675mg QD for 3 days
675 x 4 times a day= 12,700mg daily x 3 days = 8,100mg = approximately
17 tablets
17 tablets x Php90.30 = Php1,535.1
Simplotan (Not available locally)

BASES FOR COST

ORNIDAZOLE Recommended Dosage:

++ 25mg/kg as a single daily dose for 5-10 days
Weight: 15kg
Preparation: 500mg
Price: Php181.00
15 x 25 = 375mg as a single dose
375 x 5 days= 1,875mg daily = approximately 4 tablets
4 tablets x Php181.00 = Php 724.00
(Not available locally)
9

Efficacy

Aminoglycoside Pharmacodynamics:
(paromomycin)
 Aminoglycoside antibiotic used as a luminal amebicide and may be
superior to diloxanide in asymptomatic infection.
 It is used only as a luminal amebicide and has no effect against
extraintestinal amebic infections.
 Shares the same mechanism of action as neomycin and kanamycin
(binding to the 30S ribosomal subunit) and has the same spectrum of
antibacterial activity.

Pharmacokinetics:

 It is not significantly absorbed from the GI tract thus the actions of an

oral dose are confined to the GI tract.
 Small amount absorbed is slowly excreted unchanged, mainly by
glomerular filtration.
 Plasma half life: unknown

Safety

Aminoglycoside  Adverse effects include occasional abdominal distress and diarrhea.

(paromomycin)  Systemic absorption in renal insufficiency may lead to headaches,
dizziness, rashes, and arthralgia.

Suitability
 Aminoglycoside  Not available in the Philippines
(paromomycin)  Contraindications: allergy, intestinal obstruction
 Precautions: increase risk of development of drug resistance bacteria and
ototoxicity
 Convenience: (oral) 25-35 mg/kg/day, in 3 divided doses with meals for 5
to 10 days. Poorly absorbed from the GI tract

Cost

Aminoglycoside Individual cost:

(paromomycin)
 Recommend dose: 25 to 35 mg/kg/day orally in 3 divided doses with
meals for 5 to 10 days
 (25-35 mg/kg x 15kg) / 3 doses =125-175 mg/dose
 125-175 mg/dose x 5-10 days = 625(-1250) - 875(-1750) mg
 1 cap = 250 mg
 625(-1250) - 875(-1750) mg / 250 mg/cap = 2.5(-5) - 3.5(-7) caps

Total cost:

 1 bottle (42 caps) = $68.30 (3,528.38); $1.63/cap (84.2php) WITHOUT

SHIPPING FEE