Pediatric Infectious Diarrheal Disease and Dehydration

Key Concepts

Identification of Pathogen

Stool studies are not indicated in most uncomplicated cases of acute gastroenteritis (AGE). Exceptions are those cases in which specific treatment, specific prophylaxis, or health precautions are required, or in which the patient has systemic involvement, underlying medical complications, or dysenteric features.
Antibiotics are not required for most cases of uncomplicated acute bacterial enteritis. Antibiotics are recommended routinely for C. difficile, Giardia intestinalis, and E. histolytica. Antibiotics can be considered for Campylobacter , Cryptosporidium, traveler’s diarrhea, and Shigella (because antibiotics have been shown to decrease diarrhea and eradicate organisms in the stool).
Patients with Shiga toxin–producing E. coli (STEC) should not empirically receive antibiotics, because they may increase the risk of hemolytic-uremic syndrome (HUS).
Testing for fecal leukocytes is a useful initial test because it may support a diagnosis of invasive disease. This test should be considered in children with diarrhea who are febrile or have mucus or blood in the stool. If the test result is positive, stool culture is indicated to further guide management.

Oral Rehydration

Most patients with mild to moderate dehydration can be treated with oral rehydration therapy (ORT). Resumption of feeding with age-appropriate diets should begin as soon as vomiting subsides. Routine fasting with infectious diarrhea is not recommended.

Dehydration Assessment

The degree of volume depletion is estimated from the history and physical examination findings. The desired volume of oral rehydration solution is calculated as 30 to 50 mL/kg for mild dehydration and 60 to 80 mL/kg for moderate dehydration; 25% of the volume of oral rehydration solution is to be replaced every hour (100% over 4 hours). Continue to replace ongoing losses with 10 mL/kg for each diarrheal stool and 2 mL/kg for each vomiting episode. Patients who fail an oral rehydration trial of 4 to 8 hours in the emergency department (ED) should be admitted for intravenous hydration.

Severe Dehydration

In severe dehydration, 20 mL/kg of 0.9% saline (or other appropriate isotonic crystalloid solution) given intravenously or intraosseously should reverse signs of shock within 5 to 15 minutes. Repeated boluses of 20 mL/kg are indicated until clinical improvement occurs, but volume requirements greater than 60 mL/kg without signs of improvement suggest other conditions, such as septic shock, hemorrhage, capillary leak with third-space fluid sequestration, and adrenal insufficiency. Rapid correction of sodium derangements in dehydration can lead to central nervous system complications.

Diarrhea

Foundations

Background and Importance

Acute infectious diarrhea is a common illness seen around the world. Acute diarrhea is generally self-limiting in industrialized nations but can have significant morbidity and mortality for the elderly, very young, and immunocompromised patients. In underdeveloped countries, diarrheal diseases are a significant cause of death. According to the Global Burden of Disease Study 2016, diarrhea was found to be the eighth leading cause of death among all ages, responsible for more than 1.6 million deaths worldwide. Approximately half a million of the deaths from diarrhea worldwide occurred among children younger than 5 years of age, making it the third leading cause of death in children less than 5 years of age globally. ^, The rotavirus vaccine in the United States and internationally has markedly reduced pediatric diarrhea-associated emergency department (ED) visits, hospitalizations, and deaths.

Acute diarrhea is defined as the abrupt onset of abnormally high fluid content in the stool, with increased volume or frequency. As supported by the World Health Organization (WHO), “acute” diarrhea has a sudden onset and lasts no longer than 14 days; “chronic” or “persistent” diarrhea lasts longer than 14 days. This classification is important for epidemiologic studies and to identify the most likely offending organism. Protracted diarrhea has different causes, poses unique problems in management, and has a prognosis different from that of acute diarrhea. Acute infectious diarrhea can occur with or without vomiting. When it occurs with vomiting, it is often referred to as acute gastroenteritis (AGE).

Anatomy, Physiology, and Pathophysiology

Up to 9 L of exogenous fluid and endogenous secretions enter the adult proximal bowel each day, and proportionally even more in children. Ninety percent of fluid is absorbed in the small bowel and the remainder in the large bowel. Water follows osmotic gradients created by active and passive transport of electrolytes, sugars, and amino acids into the bloodstream by the following mechanisms:

Sodium chloride absorption in the small bowel, with an exchange of cations (Na ⁺ /H ⁺ ) and anions (Cl ⁻ /HCO ₃ ⁻ ).
Electrogenic sodium absorption in the colon, but also in the small intestine, wherein Na ⁺ enters the cell through an electrochemical gradient; this mechanism is often damaged in acute diarrhea.
Sodium co-transport mechanism in the small bowel. Na ⁺ absorption is coupled with the absorption of glucose, amino acids, and peptides. This mechanism often remains intact during acute diarrhea illness, making oral rehydration possible.

Pathophysiology

Infectious agents cause diarrhea by adherence, mucosal invasion, enterotoxin production, and cytotoxin production. Under normal circumstances, the absorptive processes for water and electrolytes predominate over secretion, resulting in net water absorption. Diarrhea occurs when this balance is disrupted, either as a result of increased secretion from the gastrointestinal tract, decreased absorption of fluids, or from inflammation.

Secretory diarrhea is the result of increased intestinal secretion of water into the gut lumen or an inhibition of absorption. For example, Vibrio cholera produces an enterotoxin, resulting in increased chloride and bicarbonate secretion . Secretory diarrhea is characterized by the absence of expected reduction in stool volume with fasting, a stool pH above 6, and the absence of reducing substances in the stool. Other bacteria that produce enterotoxins include Salmonella, Shigella, Escherichia coli, and Clostridioides difficile .

Osmotic diarrhea is caused by the presence of poorly absorbed solutes from altered bacterial gut flora, damage to the mucosal absorptive surface, or ingestion of substances. These substances create an osmotic gradient across the bowel lumen, resulting in intraluminal movement of water and electrolytes. Typical acute viral gastroenteritis produces injury to the small bowel epithelium with consequent disruption of microvilli, decreasing the absorptive area, and preventing normal fluid, electrolyte, and nutrient absorption. The illness is compounded if the colon is unable to compensate for the large fluid volume. Osmotic diarrhea is often characterized by diarrhea that decreases or stops with fasting, a stool pH below 6, and the presence of reducing substances in the stool.

Inflammatory processes can cause destruction of villous cells or dysfunction of cellular transporters, leading to loss of fluids and electrolytes, as well as mucus, proteins, and blood in the intestinal lumen. Dysentery, diarrhea associated with blood and mucus in the stool, implies a compromised bowel wall. Acute inflammation, caused by enteroinvasive organisms such as Salmonella, Shigella, and Campylobacter, leads to infiltration of the gastrointestinal tract by neutrophils, which release a host of enzymes and factors causing both increased secretion and decreased absorption by the intestinal tract. Although blood loss may be clinically appreciable, it is usually less significant than fluid and electrolyte losses. Infectious diarrhea can present with significant signs of dehydration and electrolyte abnormalities.

Pediatric patients have several physiologic factors that predispose them to more severe complications from vomiting and diarrhea. As a result of their relatively larger extracellular fluid compartments, children can lose proportionately more fluids through the gastrointestinal tract. Furthermore, the turnover of fluids and solute in infants and young children can be three times that of adults. This rapid turnover of fluids is the result of higher metabolic rates, increased body surface area to mass index, and higher body water content. Children also have limited stores of metabolic substrates such as fat and glycogen, limited ability or desire to access fluids when ill, and a more limited ability to conserve water through their kidneys compared to adults. These factors make children more susceptible to large fluctuations in fluid, electrolytes, and nutrients, resulting in hypoglycemia, electrolyte abnormalities, dehydration, and shock.

Some groups are at higher risk for developing serious complications of infectious diarrhea (e.g., invasive disease, bacteremia, and sepsis). These include premature infants, very-low-birth-weight infants (up to a year), young infants (younger than 3 months old), immunosuppressed or malnourished children, and those with chronic underlying conditions. Recent hospitalization, treatment with broad-spectrum antibiotics, and travel to developing countries are additional risk factors.

Clinical Features

Infectious diarrhea can present with diarrhea alone or accompanied by vomiting (i.e., acute gastroenteritis [AGE]). Signs and symptoms usually begin 12 to 72 hours after contracting the infectious agent. If due to a viral agent, the condition usually resolves within 1 week. See Box 167.1 for a list of common signs and symptoms. The history and physical examination should help differentiate acute infectious diarrhea from other causes of vomiting and diarrhea and help estimate the degree of dehydration. History and physical examination can sometimes aid in determining the type of pathogen responsible, although this will rarely affect management. Box 167.2 summarizes important information to gather from the history.

BOX 167.1

Common Signs and Symptoms in Patients With Acute Infectious Diarrhea

Diarrhea—frequent, loose, watery, mucousy, bloody, or foul smelling
Nausea
Decreased appetite
Weight loss
Vomiting
Headache
Abdominal pain or cramps
Fever
Malaise
Signs of dehydration (see Dehydration section)

BOX 167.2

Patient History

Behavior: Weight loss, amount and frequency of feeding, level of thirst, level of alertness, level of activity, lethargy, irritability, quality of crying, presence or absence of tears with crying, frequency of wet diapers in infants or urination in children
Orthostatic symptoms
Diarrhea: Duration, frequency, and amount of stools; consistency and content of stool; watery, blood, mucus
Vomiting: Duration, amount and quality of the vomitus, time since last vomited
Abdominal pain: Location, quality, radiation, severity per parent and child
Signs of infection: Fever, chills, myalgia, rash, rhinorrhea, sore throat, cough
Symptoms in relationship to eating and drinking
Similar symptoms in other household members or school
Similar episodes in the past
Food history
Water exposure and recent camping
Travel to endemic or epidemic areas
Household pets
Past medical history; chronic medical problems, recent hospitalizations; vaccine status
Current/recent antibiotic

Vital signs should be assessed relative to age norms. The evaluation of the child should begin with looking at the child from across the room in a position of comfort, noting the patient’s overall appearance, responsiveness, activity, and work of breathing (see Chapter 160 ). A head-to-toe physical examination of the patient should focus on signs of dehydration that may indicate another cause for the diarrhea (e.g., otitis media, pyelonephritis, appendicitis, diabetic ketoacidosis), or signs that indicate the disease may have become extraintestinal or systemic—bone pain (osteomyelitis), altered mental status (meningitis), petechiae (hemolytic-uremic syndrome [HUS]).

Acute infectious diarrhea in developed countries is often self-limited. The clinical presentation, course of illness, and treatment depends on the etiology of the diarrhea and the host. In the United States, viruses are responsible for most cases of acute infectious diarrhea, with bacteria causing only 7% to 10% of cases in children. Parasites are uncommon in the immunocompetent patient, unless they have traveled to endemic areas. Table 167.1 lists the most common viruses, bacteria, and protozoa that can cause acute infectious diarrhea in children in the United States.

TABLE 167.1

Common Causes of Childhood Infectious Diarrhea in Developed Countries

Viruses (70% to 80%)	Bacteria (10% to 20%)	Protozoa (<10%)
Rotavirus Norovirus and Sapovirus Astrovirus Adenovirus	Salmonella species Shigella species Campylobacter jejuni Yersinia enterocolitica Escherichia coli ; ETEC, Clostridium perfringens Clostridium difficile Staphylococcus aureus Vibrio cholera Vibrio parahaemolyticus	Cryptosporidium Giardia intestinalis Entamoeba histolytica

ETEC, Enterotoxigenic E. coli .

Specific Etiologies

Viruses

In the United States and Europe, the majority of cases of diarrhea are caused by viral pathogens, with incidence peaking in the winter. The most common of these are rotavirus and norovirus. See Table 167.2 for presentation and associated characteristics.

TABLE 167.2

Viruses Causing Diarrheal Illness: Characteristics and Associated Symptoms

Data from: World Gastroenterology Organization. World Gastroenterology Organization global guidelines: acute diarrhea in adults and children: a global perspective . Available at: www.worldgastroenterology.org/guidelines/global-guidelines/acute-diarrhea/acute-diarrhea-english ; and Kimberlin DW, Brady MIT, Jackson MA, Long SS, editors. Red Book: 2018-2021 Report of the Committee on Infectious Disease , 31st ed. Itasca, IL; American Academy of Pediatrics; 2018.

	Age	Season	Lasts	Incubation Period	How Spread	Length of Excretion	Abdominal Pain	N/V	Fever	Diarrhea Characteristics	Diagnostics
Rotavirus	<5 years old	Winter and spring	4 to 8 days	Less than 48 hours (1 to 3 days)	Mainly Fecal-oral (can stay on surfaces for weeks to months) or respiratory secretions	Up to 21 days	±	++	± 1⁄3 have high fever	Watery; large volume	ELISA and latex agglutination most commonly used; PCR most sensitive
Norovirus	<5 years old	Anytime; colder months	2 to 3 days (up to 5 days)	12 to 48 hours	Fecal-oral; contaminated food and water	5 to 7 days after onset of symptoms; up to 3 weeks	++	++ (some may not vomit)	±	Abrupt onset; watery	RT-PCR testing available; CIDT
Astrovirus	<4 years old	Late winter; early spring	2 to 5 days	1 to 4 days	Fecal-oral	Few days after symptoms resolve	±	+	++	Watery; large volume	CIDT now available
Adenovirus	<4 years old	All year	5 to 12 days	3 to 10 days	Fecal-oral	Most contagious first few days; asym excretion for months	±	+	Low grade	Watery	Commercial test available

Key: ++, common; +, occurs; ±, variable.

N/V, Nausea/vomiting ; ELISA, enzyme-linked immunosorbent assay; PCR, polymerase chain reaction; RT-PCR, reverse transcription polymerase chain reaction; CIDT, culture-independent diagnostic test.

Rotavirus (RV) continues to be the leading cause of diarrhea and significant morbidity worldwide among children younger than 5 years old. Neurologic symptoms, most commonly seizures, occur in 2% to 3% of children with rotavirus infection. The chronically ill or malnourished child often fails to repair damaged intestinal epithelium post rotavirus infection, leading to a vicious cycle of malnutrition and progressive epithelial injury.

With the introduction of the rotavirus vaccine, there has been a significant decrease in the incidence of RV in the United States. According to the CDC, norovirus is now the most common cause of diarrheal illness in children. Two live rotavirus oral vaccines, RotaTeq (RV5) (Merck & Co., Inc.) licensed in 2006 and Rotarix (RV1) (GlaxoSmithKline Biologicals) licensed in 2008, are now approved and are given widely for prevention of rotavirus gastroenteritis. Since the introduction of the RV vaccine in the U.S., a biennial pattern has emerged, with small, short seasons in late winter/early spring, and annual hospitalizations have declined among U.S. children younger than 5 years of age by 80% to 90%. ^, It is estimated that since the introduction of the RV vaccine, an estimated 177,000 hospitalizations, 242,000 ED visits, and 1.1 million outpatient visits for diarrhea have been averted among children younger than 5 years of age. The decrease in hospitalization and ED visits is also decreasing in many other countries as the use of the RV vaccine spreads globally. ^,

The current rotavirus vaccines were not associated with intussusception in large pre-licensure trials. There continues to be controversy over whether an increase in intussusception does occur. Some post-licensure studies done in the United States, Canada, Korea, Africa, Brazil, and Taiwan agree with the prelicensure trials showing no increase in intussusception with the RV vaccines. However, recent postlicensure surveillance data in the United States and internationally indicate there is an increased risk of intussusception from the currently licensed RV vaccines. These studies found that most of the increased risk occurs within the first week after the first dose but may occur up to 21 days after the first dose. Although there may be a slight increased risk of intussusception following the oral vaccines, the Centers for Disease Control and Prevention (CDC) and the World Health Organization still recommend the rotavirus vaccine as the benefits of the RV vaccine in preventing severe RV disease far outweigh the risk of intussusception. Parents should be made aware of the risk, the early signs and symptoms of intussusception, and the need for prompt care if they develop.

Human Caliciviruses (Norovirus and Sapovirus)

According to the CDC Burden of Norovirus Illness in the United States, each year, norovirus causes approximately 20 million cases of acute gastroenteritis, leading to 1.7 to 1.9 million outpatient visits and 400,000 ED visits, primarily in young children. It also contributes to about 56,000 to 71,000 hospitalizations and 570 to 800 deaths, mostly among young children and the elderly. Norovirus is now the leading cause of acute gastroenteritis among U.S. children less than 5 years of age. Norovirus AGE is associated with more frequent and prolonged vomiting, but less fever, than AGE caused by rotavirus. Seizures are the most common central nervous system (CNS) complication, whereas encephalopathy is possible but rare. Clinical manifestations for sapovirus are similar to those of norovirus .

Astrovirus has a worldwide distribution and has been found in up to 17% of sporadic cases of nonbacterial AGE in children. It accounts for only 2.5% to 9% of severe childhood AGE requiring hospitalization. In healthy children, it is an illness of short duration, although asymptomatic shedding continues up to several weeks after symptom resolution. In the immunocompromised patient, astrovirus infections have been associated with extraintestinal disease, encephalitis, and meningitis. ^,

Adenovirus is well known for causing infections of the respiratory tract along with pharyngitis, otitis media, and pharyngoconjunctival fever. Enteric adenovirus serotypes (31, 40 and 41) cause gastroenteritis, accounting for 2% to 4% of cases of acute infectious diarrhea in children. In healthy people, infection with one adenovirus type may confer type-specific immunity or at least lessen symptoms associated with reinfections. Asymptomatic shedding of the virus for months is common.

The mainstay for treatment of viral enteritis is supportive care with rehydration and electrolyte correction.

Bacteria

The common bacterial organisms causing acute diarrhea in U.S. children along with their presentations and associated characteristics are listed in Table 167.3 , and their treatment is listed in Table 167.4 .

TABLE 167.3

Bacteria Causing Diarrheal Illness: Characteristics and Associated Symptoms

Data from: World Gastroenterology Organization. World Gastroenterology Organisation global guidelines: acute diarrhea in adults and children: a global perspective . Available at: www.worldgastroenterology.org/guidelines/global-guidelines/acute-diarrhea/acute-diarrhea-english ; and Kimberlin DW, Brady MIT, Jackson MA, Long SS, editors. Red Book: 2018-2021 Report of the Committee on Infectious Disease , 31st ed. Itasca, IL; American Academy of Pediatrics; 2018.

	Who Affected	Incubation (range)	Duration of Illness	How Spread	Length of Excretion	Abdominal Pain	N/V	Fever	Diarrhea Characteristics	Other Characteristics	Diagnostic Tests
Salmonella species	<4 years old	12 to 36 hours (6 to 72 hours)	2 to 7 days	Foods from animals; contaminated water; infected reptiles, amphibians, rodents, and mammals	Up to 12 weeks in children <5 years old	++	+	++	Mild to severe; can have blood or mucus	Bacteremia can occur, focal infections in 10%	Stool culture; CIDT starting to be used
Salmonella typhi	Travelers	7 to 14 days (3 to 60 days)	Requires antibiotics	Contaminated food or water	Chronic carriers	++	+	++	Not main problem; mild diarrhea	Gradual onset; HA, malaise, anorexia; HSM, rose spots, dactylitis, ams	Blood, bone marrow, or bile culture
Shigella species	≤5 years old	1–3 (1 to 7 days)	48 to 72 hours	Fecal-oral, contaminated food/ water, objects	1 to 4 weeks, antibiotics may shorten excretion	++	++	++	Mild to severe: watery to mucoid with or without blood	Can have systemic symptoms; neurological symptoms; tenesmus Fecal PMNs often positive	Stool culture; improved with fresh stool, CIDT have high sensitivity; high false-positive rate
Campylobacter	<4 years old	2 to 5 days	5 to 7 days; 15% can relapse or have prolong or severe disease	Ingestion of contaminated foods; fecal-oral in the very young; greatest in acute phase	2 to 3 weeks without treatment 2 to 3 days with treatment	+ + Can mimic appendicitis or intussusception	+	++ Infants may not have fever	Watery to mucoid/bloody	Malaise; can have febrile symptoms before GI symptoms Infants may have bloody diarrhea and no fever Can mimic acute inflammatory bowel disease	C. jejuni and C. coli from stool culture; CIDT, don’t differentiate species
Yersinia enterocolitica	<5 years most common	4 to 6 days (1 to 14 days)	Variable; usually few days but diarrhea up to 2 weeks	Contaminated food or water; contact with animals, person to person is rare	Average 2–3 weeks (up to 2–3 mos if untreated)	+	±	++	Often with blood and mucus	Pseudoappendicitis syndrome Fecal PMNs often positive Bacteremia; <1 year old, excessive iron storage, immunosuppressed	Stool culture; need to specify
Clostridium difficile	>24 months	Not really known. Colitis usually starts 5 to 10 days after starting antibiotics (up to 10 weeks)	Variable	Fecal-oral or environment	Unknown	+	−	+ Low grade	Mild: watery diarrhea to pseudomembranous colitis; mucus in stool		EIA detection of toxins NAAT good sensitivity and specificity
Clostridium perfringens	Any age	8 to 12 hours (6 to 24 hours)	24 hours	Catered foods	As long as illness persists	++ Crampy, epigastric	−	−	Sudden onset; watery diarrhea	Common in healthy people’s stool Treatment not necessary; short course	High spore count in stool Commercially available kits
Staphylococcus aureus	Any age	2 to 4 hours (30 minutes to 8 hours)	1 to 2 days	Contaminated food that remains at room temperature for hours	Short time	+	++	± Low grade	Watery	Violent onset of nausea/vomiting; can have mild hypothermia	Culture stool or vomitus EIA or PCR detect enterotoxin
Vibrio cholera	Traveled to endemic area	1 to 3 days (hours to 5 days)	3 to 7 days	Contaminated food and water (shellfish; raw vegetables)	Short time	±	±	±	Large amounts watery diarrhea; stool colorless with flecks of mucus; rice water appearing	Dehydration, hypokalemia, metabolic acidosis and shock within 4 to 12 hours; coma, seizures, hypoglycemia	Stool culture; need to request
Vibrio parahaemolyticus	All ages	23 hours (5 to 92 hours)	2 to 5 days	Seawater; undercooked seafood	Not excreted	++	±	± Low grade	Acute onset Watery stools	Liver disease, low gastric acidity, immunosuppressed increased risk	Lab needs to be notified when test; can test stool, blood, or wounds
E. coli (STEC)	All ages	3 to 4 days (1 to 8 days)	Usually 7 days	Contaminated food or water with human or animal feces; person to person occurs		++	+	− Sometimes low grade	Bloody or nonbloody	Stool becomes bloody after 3 to 4 days; can cause HUS Shiga toxin produced	Stool culture; must request test for E. coli O157 EIA for Shiga toxin if available
E. coli (EPEC)	<2 years old; RLAs and travelers	10 hours to 6 days	Usually few days but variable	Contaminated food or water with human or animal feces		−	−		Watery, usually mild	Can become chronic and cause growth retardation No toxin produced	Not widely available
E. coli (ETEC)	Infants in RLAs and travelers of all ages	10 hours to 6 days	1 to 5 days	Contaminated food or water with human or animal feces; person to person occurs		+	−	±	Watery	Uncommon in the U.S. Enterotoxin produced	Not widely available
E. coli (EIEC)	All ages	10 hours to 6 days	Variable	Contaminated food or water with human or animal feces		±	−	+	Usually watery without blood or mucus; dysentery can occur	Related to Shigella can cause similar dysenteric illness	Not widely available
E. coli (EAEC)	All ages	10 hours to 6 days	Variable	Contaminated food or water with human or animal feces		±	−	±	Watery, occasionally bloody	Enterotoxin and cytotoxin Associated with prolonged diarrhea; becoming more common in U.S.	Not widely available

Key: ++, common; +, occurs; ±, variable; −, not common.

CIDT, Culture-independent diagnostic test ; EAEC, enteroaggregative Escherichia coli; EIA, enzyme immunoassay; EIEC, enteroinvasive E. coli; EPEC, enteropathogenic E. coli; ETEC, enterotoxigenic E. coli; HA, headache; HUS, hemolytic-uremic syndrome; GI, gastrointestinal; NAAT, nucleic acid amplification test; N/V, nausea/vomiting; PCR, polymerase chain reaction; PMN, polymorphonucleocyte; RLA, resource limited area; STEC, Shiga toxin–producing E. coli

TABLE 167.4

Treatment Recommendations for Common Bacteria Causing Acute Infectious Diarrhea in Children

Data from: Kimberlin DW, Brady MIT, Jackson MA, Long SS, editors. Red Book: 2018-2021 Report of the Committee on Infectious Disease , ed 31. Itasca, IL: American Academy of Pediatrics; 2018; and Hughes HK, Kahl LK, editors. The Harriet Lane Handbook: A Manual for Pediatric House Officers , ed 21. Philadelphia: Saunders; 2018.

	Routine Treatment	Treatment Indicated—High-Risk Groups	Antibiotic	Comments
Salmonella non-typhi	No; treatment prolongs excretion; does not shorten disease	Infants <3 months old, prolonged illness, chronic GI disease, neoplasms, hemoglobinopathies, HIV, immunosuppression, localized invasive disease (osteomyelitis, abscess, meningitis) or bacteremia	Susceptibility is known Oral: Amoxicillin 25–50 mg/kg divided every 8 hours IV: Ampicillin 200 mg/kg divided every 6 hours (max 8 g/d) Oral: TMP-SMX 10 mg/kg divided every 12 hours (max 160 mg/dose) Susceptibility not known or areas of high resistance or invasive disease or bacteremia IV or IM: Ceftriaxone 50–75 mg/kg q24h (max 2 g) or Oral or IV: Azithromycin 10–20 mg/kg (max 500 mg/dose) or Oral: Adult— ^a Ciprofloxacin 500 mg/dose every 12 hours, Children— ^a Ciprofloxacin 20–40 mg/kg divided every 12 hours (max 1 g/day)	Blood cx before initiating antibiotics. Bacteremia: Treat for 10 to 14 days Localized invasive disease: Treat for 4 weeks (6 weeks if meningitis) and begin with IV medications Aminoglycosides not recommended for invasive disease Drug of choice, route of administration, and duration of therapy based on susceptibility of organisms, site of infection, host and clinical response
Salmonella typhi	Yes	All patients with enteric fever Delirium, stupor, coma, or shock	Start with IV medications; change to oral when susceptibility is known Ceftriaxone 50– 75 mg/kg q24h (max 2 g) or ^a Ciprofloxacin 20–40 mg/kg divided every 12 hours(max 1g/day)	Multidrug resistance is common 10- to 14-day treatment Check susceptibilities Azithromycin for uncomplicated disease Consider: Dexamethasone IV 3 mg/kg, followed by 1 mg/kg every 6 hours for 48 hours; relapse is common
Shigella species	No; usually self-limited but treatment decreases diarrhea and eradicates organism from stool	Severe disease, bacteremia, dysentery, immunosuppression Less ill and able to tolerate PO (See Oral dosing)	IV: Ceftriaxone 50 mg/kg (max 2 g) for 5 days (≥ 17 years old) or ^a Ciprofloxacin 20–30 mg/kg/day divided bid or Azithromycin 20 mg/kg/day (max 500 mg) Oral: Azithromycin 12 mg/kg for first day, then 6 mg/kg for days 2 to 5 or ^a Ciprofloxacin 20 mg/kg divided every 12 hours for 5 days	Oral route preferred when possible and disease is not serious TMP-SMX and ampicillin only if isolated strain is susceptible because of high resistance Amoxicillin less effective because of rapid absorption from GI tract; avoid fluoroquinolones if MIC >0.12 even if says susceptible.
Campylobacter jejuni	Variable	Variable recommendations. Most children will resolve on own.	Oral: Azithromycin 10 mg/kg for 3 days (max 500 mg/dose) or Erythromycin 40 mg/kg/day divided every 6 hours (max 2g/day) for 5 days	Shorten duration of illness and excretion of organisms and prevent relapse if given early Resistance to fluoroquinolones is frequent
Yersinia enterocolitica	No; although can be considered as it decreases shedding of the organism;	Neonates, septicemia or extraintestinal sites of infection; immunocompromised host	Oral: TMX-SMX 10 mg/kg divided every 12 hours or Oral or IV fluoroquinolone ^a , 10 mg/kg/day of TMP component: Ciprofloxacin 20 mg/kg divided every 12 hours or IV: Ceftriaxone 50 mg/kg qd	Usually resistant to penicillin and first generation cephalosporins Antibiotics do decrease the duration of fecal excretion but do not decrease length of diarrhea Extraintestinal disease treat for 4 weeks. Usually susceptible to tetracycline and doxycycline
C. difficile	Yes	Symptomatic patients Severe disease, underlying intestinal tract disease, and those who don’t respond to oral metronidazole use vancomycin	Stop antimicrobial therapy Oral or IV: Metronidazole 30–40 mg/kg/day for at least 10 days (maximum dose 500 mg/dose) if failure to respond in 5 days then: Oral: Vancomycin 40 mg/kg /day divided every 6 hours for at least 10 days (maximum 125mg/dose	25% relapse after treatment, usually responds to second course; IV vancomycin is not effective Do not give antimotility agents; if no abdominal distention and severe disease use Vanco PO and metronidazole IV. If ileus or toxic colitis add vancomycin (1–3 years old: 250 mg/50 mL q6h; 4–9 years old: 375 mg/75 mL q6h; ≥10 years old: 500 mg/100 mL q6h) NS enema until improved
Vibrio cholera	No	Patients with moderate to severe disease	Oral: Doxycycline ^a 4.4 mg/kg/day divided bid or Azithromycin 20 mg/kg single dose or Tetracycline ^a 50 mg/kg/day divided every 6 hours (maximum 3 g/day) for 3 days	Susceptibility testing recommended Treatment decreases duration of diarrhea and eradicates bacteria from stool; Cipro not recommended in children high treatment failures
V parahaemolytica	No	Severe diarrhea, septicemia Consider in patients <8 years old	Third-generation cephalosporin and doxycycline ^a TMX-SMX and aminoglycoside
E. coli	No for STEC infection or concern for STEC	Severe watery diarrhea in a traveler to RLA	Azithromycin 10 mg/kg qd ×3 days, ciprofloxacin 30 mg/kg/day divided BID ×3 days ^a	Treating patients with STEC may increase risk for HUS

GI, Gastrointestinal; HIV, human immunodeficiency virus; HUS, hemolytic-uremic syndrome; IM, intramuscular; IV, intravenous; PO, per os (by mouth); RLA, resource limited area; STEC, Shiga toxin–producing E. coli, TMP-SMX, trimethoprim-sulfamethoxazole.

a Fluorquinolone: ciprofloxin recommended for greater or equal to 17 years unless benefits outweigh the risks. Tetracyclines/doxycyclines are not recommended in children younger than 8 years because of teeth staining, but the benefit of using the drug may outweigh the risk of teeth staining. Each case is considered separately. Ciprofloxacin recommended for greater or equal to 17 years unless benefits outweigh the risks.

Nontyphoidal Salmonella (NTS) is the most common cause of laboratory confirmed cases of enteric disease. The CDC estimates that approximately 1.35 million illnesses and 420 deaths occur annually in the United States due to NTS. In a recent study, the most commonly reported human isolates were Salmonella Enteritidis, Typhimurium, Newport, Heidelberg, and Javiana; these 5 serotypes accounted for 62% of U.S. Salmonella infections. The incidence of NTS is highest in children less than 4 years of age. Infection can result in an asymptomatic carrier state, AGE, bacteremia, invasive disease, or a disseminated abscess syndrome.

Salmonellae invade the mucosa of the distal small intestine and the colon; they produce a cholera-like enterotoxin and a cytotoxin, which can cause significant diarrhea and fluid and electrolyte abnormalities similar to patients with documented cholera. Fever in NTS patients usually lasts about 48 hours, and patients with prolonged fever may have intermittent bacteremia. Patients with Salmonella bacteremia are at increased risk for developing extraintestinal infections, seen in up to 10% of patients with Salmonella bacteremia. Infants, the elderly, patients with hemoglobinopathies, and the immunosuppressed are at highest risk for invasive disease. Extraintestinal sites of infection can result in endocarditis, vascular infections, cholecystitis, hepatic and splenic abscesses, urinary tract infections, pneumonia, meningitis, septic arthritis, and osteomyelitis.

Although uncommon, Salmonella serotype typhi is only found in humans and can cause a bacteremic illness often referred to as enteric or typhoid fever. Although uncommon in the United States, S. typhi is endemic in many resource-limited countries. Typhoid fever may be acquired during international travel and appear as a nonspecific febrile illness in young children in whom sustained or intermittent bacteremia may occur. Constipation can be the presenting symptom and is often seen early in the course of the disease, but diarrhea can also occur. If S . typhi is suspected, blood, bone marrow or bile should be cultured, because stool cultures are often negative.

Treatment of noninvasive NTS infection is usually supportive. Antimicrobial treatment is only recommended for infants younger than 3 months and people with chronic gastrointestinal disease, malignant neoplasms, hemoglobinopathies, HIV infections, or other immunosuppressive illnesses or therapies. If treatment is started for presumed disease, stool and blood cultures should be obtained prior to initiating antibiotics. On the other hand, for children with S. typhi infection, antibiotics are recommended. Relapse of enteric fever occurs in up to 17% of patients and requires retreatment. Treatment failures have occurred in people treated with cephalosporins, aminoglycosides, and furazolidone, despite in vitro testing indicating susceptibility.

Among Shigella isolates reported in industrialized nations, most are Shigella sonnei (84%). Shigella flexneri, Shigella boydii, and Shigella dysenteriae account for the remainder. S. sonnei is the most common cause of dysentery in the United States. Extraintestinal symptoms and signs are relatively common in children with Shigella infection, including hallucinations, confusion, and seizures. Reactive arthritis (Reiter syndrome) can occur weeks after the infection. Rare complications of Shigella infection include bacteremia, HUS, toxic megacolon, pseudomembranous colitis, and encephalopathy (Ekiri syndrome). The risk of septicemia increases in neonates, malnourished children, and with S. dysenteriae. There is some evidence that antibiotic treatment is effective in shortening duration of diarrhea and hastening eradication of organisms from feces. Drug-resistant Shigella has been rapidly increasing; resistance to first-line drugs, ampicillin and trimethoprim-sulfamethoxazole, has become so high that emergency clinicians must rely on alternative drugs like ciprofloxacin and azithromycin. However, over the last 5 years, resistance to these medications has also increased drastically. According to the CDC, both ciprofloxacin and azithromycin resistance has increased from approximately 2% to over 20%. Of particular concern are frequently reported outbreaks of multidrug-resistant Shigella among men who have sex with men. ^,

Campylobacter species cause a significant proportion of diarrheal disease worldwide, with 1.5 million annual U.S. cases and children younger than 5 years most commonly infected. Of the five types, C. jejuni and C. coli are the most common. ^, In neonates and young infants, bloody diarrhea without fever can be the only manifestation of infection. Febrile seizures can occur in young children before any gastrointestinal symptoms are present. The clinical presentation may be similar to acute appendicitis or intussusception. Severe or prolonged disease can mimic inflammatory bowel disease. Bacteremia is uncommon but can occur in children, including neonates. Immunocompromised hosts can have prolonged, relapsing, or extraintestinal infections. Immunoreactive complications include Guillain-Barré syndrome, reactive arthritis, myocarditis, pericarditis, and erythema nodosum. Antibiotic treatment is recommended for those with severe invasive disease, those at increased risk for severe disease, and for those with prolonged excretion of the bacteria. According to the CDC and the World Health Organization, most healthy children will recover without antibiotic treatment. Azithromycin and erythromycin do shorten the duration of the illness and excretion of the organisms if susceptible. Resistance to antibiotics is increasing. Over 10% of isolates are resistant to azithromycin and erythromycin and over 35% are resistant to ciprofloxacin in the United States. Therefore, if using culture-independent diagnostic tests (CIDT) tests to diagnosis Campylobacter , cultures are recommended to confirm diagnosis and for susceptibility information.

Yersinia enterocolitica is a relatively uncommon cause of simple self-limited diarrhea and vomiting in the United States. According to the CDC, there has been a recent increase in the incidence, most likely from CIDT results. Y. enterocolitica most often affects children younger than 5 years of age. As many as 6% of older children and adults may present with an appendicitis-like illness, with right lower quadrant tenderness, usually as a result of reactive mesenteric adenitis. Antibiotics are indicated for the immunocompromised patient with enterocolitis and in cases of septicemia or extraintestinal infections. Isolates are often resistant to first-generation cephalosporins and most penicillins. Bacteremia is the major complication of Y . enterocolitica, occurring mostly in children less than 1 year of age and in older children with predisposing conditions, including excessive iron storage (e.g., deferoxamine use, sickle cell disease, and beta-thalassemia) and immunosuppressive states. Extraintestinal manifestations of Y. enterocolitica are rare. Postinfectious sequelae include erythema nodosum, reactive arthritis, and proliferative glomerulonephritis, most often associated with older children and adults with HLA-B27.

Humans acquire C. difficile from their environment or via the oral-fecal route, which can lead to infection. The disruption of the body’s normal flora, often as a result of antimicrobial treatment, leads to overgrowth of C. difficile , toxin production, and disease development. Exposure to antibiotics is the most important risk factor for C. difficile . Penicillins, cephalosporins, clindamycin, and fluoroquinolones are associated more commonly with C. difficile infection, whereas sulfonamides, tetracyclines, vancomycin, metronidazole, and aminoglycosides are less commonly linked in children. Pediatric patients who are exposed to multiple antibiotics from different classes in the previous 30 days have been shown in recent studies to be associated with severe and recurrent C. difficile infection. Other risk factors include acid-suppressing medications, such as proton pump inhibitors, and use of gastrointestinal feeding tubes.

C. difficile infections cause a spectrum of illnesses ranging from asymptomatic to watery diarrhea to pseudomembranous colitis. Clinical illness is rare before 12 to 24 months of age. Asymptomatic infants can be colonized with C. difficile ; carriage rates vary by age and range from 37% in neonates to less than 3% by age 2 years. ^, C. difficile should be considered in children 1 to 3 years old, but only after other causes of diarrhea (particularly viral) are excluded. Endoscopic findings of pseudomembrane and friable rectal mucosa are sufficient to diagnose C. difficile at any age. This is helpful when trying to determine if a child younger than 3 years old is colonized or has disease. The endoscopic findings are diagnostic of disease. Complications include toxic megacolon and intestinal perforation. Severe or fatal disease is more common in neutropenic patients with leukemia, infants with Hirschsprung disease, and patients with inflammatory bowel disease. ^46,47,48

See Tables 167.3 and 167.4 for presentation and associated characteristics and treatment recommendations for Clostridium perfringens, Staphylococcus aureus, V. cholera , and Vibrio parahaemolyticus .

Each year, the WHO Global Burden of Foodborne Diseases reports over 300 million illnesses and nearly 200,000 deaths caused by E. coli diarrheagenic infections. E. coli , part of the normal flora in the lower gastrointestinal tract, includes five species types recognized to cause acute diarrheal disease. The enterohemorrhagic E. coli (EHEC) strain is also known as Shiga toxin–producing E . coli (STEC). While there are 50 other serotypes that can cause illness, E . coli O157:H7 is the prototype and most virulent of the EHEC and is the one more commonly reported in industrialized countries. Outbreaks have been linked to ground beef, petting zoos, contaminated apple cider, raw fruits and vegetables, and ingestion of water in recreational areas. The infectious dose is low, and person-to-person transmission does occur. In 2016, 52 state and regional public health laboratories reported 5441 cases of culture-confirmed STEC infections. Compared with 2015, the incidence of both STEC O157 and non-O157 infections in 2016 was higher (9% and 15% increase respectively).

HUS, a triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal insufficiency, is a serious complication of EHEC infection and occurs in up to 15% of children with E. coli O157:H7. The overall incidence of HUS caused by a diarrheal pathogen (usually STEC) is estimated to be 2.1 cases per 100,000 persons per year, with a peak incidence in children younger than 5 years old (6.1 cases per 100,000 per year). HUS typically develops as diarrhea is resolving, usually at 7 days but may be up to 3 weeks after the onset of the illness. Patients often present with pallor, weakness, irritability, and oliguria or anuria. Patients with HUS can develop neurologic complications, such as seizures, coma, and cerebral vessel thrombosis. Approximately 50% of patients who have HUS will require dialysis, and 3% to 5% die. Indicators that may predict poor outcome for patients with HUS include white blood cell counts greater than 20,000, oliguria or anuria, normal or high hematocrits (≥10.8 g/dl), low sodium less than 128 mEq/L, or presence of a respiratory tract infection within 3 weeks of the diagnosis.

A serious risk posed by hemorrhagic colitis is the rapid loss of fluids, which can cause electrolyte abnormalities and result in poor perfusion and end-organ damage. Patients should receive adequate amounts of intravenous (IV) fluids (or by mouth if able to take in enough) to restore intravascular volume (monitor urine output, capillary refill time, blood pressure, pulse, and mental status), and electrolyte abnormalities should be corrected. Fluids should be continued and ongoing losses replaced, with possible admission for ongoing treatment and monitoring of electrolytes, complete blood cell count, blood urea nitrogen (BUN), and creatinine. Evidence from a recent study suggests that patients with HUS who received early volume expansion (increase of body weight by 12.5%) had lower rates of central nervous system involvement, less need for dialysis or intensive care support, and fewer days of hospitalization. These patients also had significantly better long-term outcomes in renal and extrarenal sequale.

Controversy continues to exist about the indications for antibiotic treatment of STEC infections due to a possible association with an increased risk of HUS. To date, there are no controlled trials to support or disprove this association with HUS and the most recently published observation studies found that at least some classes of antimicrobial agents were associated with HUS. Experts continue to advise not prescribing antibiotics for children with E. coli 0157 enteritis or a clinical picture strongly suggestive of STEC infection, because no benefit has been found from the use of antibiotics. See Tables 167.3 and 167.4 for presentation and associated characteristics and treatment recommendations for other E. coli infections.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here