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Antibiotic Therapy in Diarrhea
M.Emadoleslami MD
• Excessive loss of fluid and electrolyte in the stool
•
•
Acute diarrhea is defined as sudden onset of excessively loose stools of
>10 mLlkg/day in infants and >200 g/24 hr in older children, which lasts
<14 days
When the episode lasts>14 days, it is called chronic or persistent diarrhea
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• Normally, a young infant has 5 ml/kg/day of stool output
• The greatest volume of intestinal water is absorbed in the small bowel; the
colon concentrates intestinal contents against a high osmotic gradient
•
Disorders that interfere with absorption in the small bowel tend to produce
voluminous diarrhea, whereas disorders compromising colonic absorption
produce lower-volume diarrhea
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Shigella
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 An acute invasive enteric infection clinically manifested by diarrhea that is
often bloody
 The term dysentery, syndrome of bloody diarrhea with fever, abdominal
cramps, rectal pain, and mucoid stools
 Bacillary dysentery is a term often used to distinguish dysentery caused by
Shigella from amoebic dysentery caused by Entamoeba histolytica
 The pathologic changes of shigellosis take place primarily in the colon
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Diagnosis
Presumptive diagnosis : fecal leukocytes (usually >50 or 100 PMNs per
high power field, confirming the presence of colitis), fecal blood, and
peripheral blood of leukocytosis, a dramatic left shift (often with more
bands than segmented neutrophils)
5,000-15,000 cells', leukopenia, eukemoid reactions
Transport media should be used if specimens cannot be cultured promptly
Multiple fecal cultures improve the yield of Shigella
In toxic children, blood cultures should be obtained, especially in very
young or malnourished infants because of their increased risk of bacteremia
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Treatment
 The first concern in a child with suspected shigellosis should be for fluid
and electrolyte correction and maintenance
 Drugs that retard intestinal motility should not be used because of the risk
of prolonging the illness
 A high-protein diet during convalescence enhances growth in the following
6 mo
 20 mg elemental zinc for 14 d, decrease the duration of diarrhea, improve
weight gain during recovery and immune response to the Shigella, and
decrease diarrheal disease in the subsequent 6 mo in malnourished children
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The Use of Antibiotics *
• Some authorities recommend withholding antibacterial therapy because of
the self-limited nature of the infection, the cost of drugs, and the risk of
emergence of resistant organisms
• Empirical treatment of all children in whom shigellosis is strongly
suspected
• Even if not fatal, the untreated illness can cause a child to be quite ill for
weeks; chronic or recurrent diarrhea can ensue
• Malnutrition can develop or worsen during prolonged illness, particularly
in children in developing countries
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**
 Shigella strains are often resistant to ampicillin and TMP-SMX
 Ceftriaxone 50 mg/kg/24 hr as a single daily dose IV
 Cefixime
 Nalidixic acid(55 mg/kg/24 hr orally divided 4 times/day) is also an
acceptable alternative drug
 Azithromycin (12 mg/kg/24 hr orally for the first day, followed by 6
mg/kg/24 hr for the next 4days)
 Ciprofloxacin (30 mg/kg/24 hr divided into 2 doses)
 Oral 1st and 2nd-generation cephalosporins are inadequate
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***
 Ciprofloxacin now the drug of choice recommended by WHO for all
patients with bloody diarrhea,irrespective of their ages
 Although quinolones have been reported to cause arthropathy in immature
animals, the risk of joint damage in children, minimal
 Some experts recommend that these agents be reserved for seriously ill
children with bacillary dysentery due to an organism that is suspected or
known to be resistant to other agents, because overuse of quinolones
promotes development of resistance to these drugs
 Treatment in general is for a 5-day course
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****
• Treatment of patients in whom Shigella infection is suspected on clinical
grounds of should be initiated when they are first evaluated
•
Stool culture is obtained to exclude other pathogens and to assist in
antibiotic changes should a child fail to respond to empirical therapy
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A child who has typical dysentery and who responds to initial empirical
antibiotic treatment should be continued on that drug for a full 5-day course
even if the stool culture is negative
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Salmonella
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• Salmonellosis is a common and widely distributed food-borne disease
• A gastroenteritis of rapid onset and brief duration, in contrast to typhoid,
which has a considerably longer incubation period and duration of illness
and in which systemic illness predominates and only a small proportion of
children get diarrhea
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Diagnosis
 On clinical correlation of the presentation and culture of and subsequent
identification of Salmonella organisms from feces or other body fluid
 Cultures of stools have higher yields than rectal swabs
 In children with nontyphoidal Salmonella gastroenteritis, prolonged fever
lasting >5 days and young age should be recognized as risk factors closely
associated with development of bacteremia
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Treatment
Infants (<3 mo of age) and that of disseminated infection in HIV,
malignancies, immunosuppressive therapy, sickle cell anemia, ), these
children must receive an appropriate empirically chosen antibiotic until
culture results are available
In children with gastroenteritis, rapid clinical assessment, correction of
dehydration and electrolyte disturbances, and supportive care, are key
Antibiotics are not generally recommended for the treatment of isolated
uncomplicated Salmonella gastroenteritis because they may suppress
normal intestinal flora and prolong both the excretion of Salmonella
Infections with suspected drug-resistant Salmonella should be closely
monitored and treated with appropriate antimicrobial therapy
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Typhoid Fever
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Diagnosis
Blood culture in the course of the disease, and stool and urine culture
results become positive after the 1st wk
The stool culture result is also occasionally positive during the incubation
period
Although bone marrow cultures may increase the likelihood of
bacteriologic confirmation of typhoid, collection of the specimens is
difficult and relatively invasive
The classic Widal test measures antibodies against 0 and H antigens of S.
Typhi but lacks sensitivity and specificity in endemic areas. Because many
false-positive and false-negative results occur, diagnosis of typhoid fever
by Widal test alone is prone to error
Despite these innovations, the mainstay of diagnosis of typhoid remains
clinical in much of the developing world, and several diagnostic algorithms
have been evaluated in endemic areas
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Treatment
• The vast majority of children with typhoid can be managed at home with
oral antibiotics and close medical follow-up for complications or failure of
response to therapy
• Patients with persistent vomiting, severe diarrhea, and abdominal distention
may require hospitalization and parenteral antibiotic therapy
• Adequate rest, hydration, and attention are important to correct fluid and
electrolyte imbalance
•
Acetaminophen 10-15 mg/kg every 4-6 hr PO
• A soft, easily digestible diet should be continued unless the patient has
abdominal distention or ileus
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 Antibiotic therapy, critical to minimize complications


Traditional therapy with either chloramphenicol or amoxicillin is associated
with relapse rates of 5-15% and 4-8%
Use of the quinolones and third-generation cephalosporins is associated
with higher cure rates

The antibiotic treatment of typhoid fever in children is also influenced by
the prevalence of antimicrobial resistance

Over the past 2 decades, emergence of multidrug-resistant strains of S.
Typhi has necessitated treatment with fluoroquinolones
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• Some investigators have suggested that children with typhoid should be
treated with fluoroquinolones like adults
• Others have questioned this approach on the basis of the potential
development of further resistance to fluoroquinolones and the fact that
quinolones are still not approved for widespread use in typhoid fever
• Supportive treatment and maintenance of appropriate fluid and electrolyte
balance
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Cholera
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Cholera is a rapidly dehydrating diarrheal disease that can lead to death, if
appropriate treatment is not provided immediately
Although rare in industrialized countries, cholera has a propensity to cause
outbreaks in areas with poor hygiene and inadequate sanitation and water
facilities
These outbreaks may be explosive, especially when they occur in
populations residing in crowded conditions, such as refugee camps
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Clinical Manifestations
Most cases of cholera are mild
Among symptomatic cases, 20% develop severe dehydration,rapidly lead
to death
Incubation period 1-3 days (several hours to 5 d), acute watery diarrhea
and vomiting ensues
The onset may be sudden, profuse watery diarrhea, but some, anorexia and
abdominal discomfort and the stool may initially be brown
Diarrhea can progress to painless purging of profuse rice-water stools with
a fishy smell, which is the hallmark of the disease
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Vomiting with clear watery fluid is usually present at the onset of the
disease
This purging leads to dehydration manifested by decreased urine output,
sunken fontanels , sunken eyes, absence of tears, dry oral mucosa, shriveled
hands and feet (washerwoman's hands), poor skin turgor, thready pulse,
tachycardia, hypotension, and vascular collapse
Patients with metabolic acidosis can present with typical Kussmaul
breathing
Although patients may be initially thirsty and awake, they rapidly progress
to obtundation and coma. If fluid losses are not rapidly corrected, death can
occur within hours
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Laboratory Findings
 Findings associated with dehydration such as elevated urine specific
gravity and hemoconcentration are evident
 Hypoglycemia is a common finding due to decreased food intake during
the acute illness
 Serum potassium may be initially normal or even high in the presence of
metabolic acidosis; however, as the acidosis is corrected, hypokalemia can
become evident
 Metabolic acidosis due to bicarbonate loss is a prominent finding in severe
cholera
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Diagnosis
 Laboratory confirmation is necessary for epidemiologic surveillance
 V. cholerae may be isolated from stools, vomitus, or rectal swabs
 Specimens may be transported on Cary-Blair media, if they cannot be
processed immediately
 Stool examination reveals few fecal leukocytes and erythrocytes because
cholera does not cause inflammation
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DX & D.DX
 In children who have acute watery diarrhea with severe dehydration and
have recently traveled to an area known to have cholera, the disease may be
suspected pending laboratory confirmation
 Cholera differs from other diarrheal disease in that it often occurs in large
outbreaks affecting both adults and children
 Diarrhea due to other etiologic causes (e.g., enterotoxigenic Escherichia
coli or rotavirus) may be difficult to distinguish from cholera clinically
 Microbiologic isolation of V. cholerae remains the gold standard for
diagnosis
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Treatment
 Rehydration, Effective and timely case management considerably decreases
mortality
 Children with mild or moderate dehydration may be treated with ORS
unless the patient is in shock, is obtunded, or has intestinal ileus
 Vomiting is not a contraindication to ORS
 Severely dehydrated patients require intravenous fluid, ideally with lactated
Ringer solution
 Feeding should not be withheld during diarrhea
 Frequent, small feedings are better tolerated than less frequent, large
feedings
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 Close monitoring during the first 24 hr of illness
 After rehydration, patients have to be reassessed every 1-2 hr, or more
frequently if profuse diarrhea is ongoing
 As soon as vomiting stops (4-6 hr after initiation of rehydration therapy),
an antibiotic must be administrated
 Zinc , as soon as vomiting stops
 Zinc supplementation among children <5 y, shorten the duration of diarrhea
and reduce subsequent diarrhea episodes when given daily for 14 d at the
time of the illness
 For children <6 mo of age, 10 mg of oral zinc daily, 2 wk
 Children aged 6 mo to 12 yr, 20 mg of oral zinc may be given daily, 2 wk
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Antimicrobials For Suspected Cholera Cases
With Severe Dehydration
Doxycycline (adults and older children)
300 mg given as a single dose
Or
Tetracycline 12.5 mg/kg/dose 4 times/day
3 days (up to 500 mg per dose, 3 days)
Erythromycin 12.5 mg/kg/dose 4 times a day, 3 days (up to 250 mg 4 times
a day x 3 days)
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o Antibiotics shorten the duration of illness, decrease fecal excretion of
vibrios, decrease the volume of diarrhea, and reduce the fluid requirement
during rehydration
o Single-dose doxycycline increases compliance; there have been increasing
reports of resistance to tetracyclines. Ciprofloxacin, azithromycin, and
TMP/SMX are also effective against cholera
o Cephalosporins and aminoglycosides are not clinically effective
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E.Coli
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Treatment
Appropriate fluid and electrolyte therapy
Oral replacement and maintenance with rehydration solution
Prolonged Withholding of feeding can lead to chronic diarrhea and
malnutrition
After refeeding, continued supplementation with oral rehydration fluids is
appropriate to prevent recurrence of dehydration
Early refeeding (within 6-8 hr of initiating rehydration) with breast milk or
infant formula or solid foods should be encouraged
In malnourished child, oral zinc should be given
Specific antimicrobial therapy of diarrheagenic E. coli is problematic
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Multiple studies in developing countries,diarrhea genic E. coli strains to be
commonly resistant to antibiotics such as TMP-SMX and ampicillin (6070%)
There are no randomized controlled studies of antibiotics for the treatment
of diarrheagenic E. coli diarrhea in children
ETEC respond to antimicrobial agents such as TMP-SMX when the E. coli
strains are susceptible. ETEC cases from traveler's diarrhea trials respond
to ciprofloxacin, azithromycin
In a child who fails to respond to therapy of a dysenteric syndrome in the
presence of initially negative stool culture results, additional cultures
should be obtained and the child should be re-evaluated for other possible
diagnoses
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However, other than for a child recently returning from travel in the
developing world, empirical treatment of severe watery diarrhea with
antibiotics is seldom appropriate
EIEC infections may be treated before the availability of culture results
because the clinician suspects shigellosis and has begun empirical therapy
If the organisms prove to be susceptible, TMP-SMX is an appropriate
choice
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