AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Escherichia coli, a facultatively anaerobic gram-negative bacillus, is a major component of the normal intestinal flora and ubiquitous in the human environment. First described in 1885, E coli has become recognized as both a harmless commensal and a versatile pathogen.

Pathophysiology

In contrast to the essential and beneficial role of most E coli isolates in the human intestine, pathogenic E coli are responsible for a broad spectrum of human disease. E coli has emerged as an important cause of diarrheal illness, with diverse phenotypes and pathogenic mechanisms. Hemolytic-uremic syndrome (HUS) is a potentially devastating consequence of enteric infection with specific E coli strains. E coli also is a commonly identified cause of urinary tract infections (UTIs) and neonatal sepsis and meningitis.

Frequency

United States

Statistics on pathogenic E coli strains reflect increasing recognition and surveillance during the past 2 decades. Recent estimates suggest that more than 100,000 illnesses annually are attributable to shiga-toxin–producing E coli, up to 50% of which are strains other than O157:H7. Enterotoxigenic and other diarrheagenic E coli strains in combination cause an estimated 150,000 or more illnesses annually.

International

Many strains of diarrheagenic E coli primarily affect developing nations. Statistics on the prevalence of the strains vary by location. Worldwide, enterotoxigenic E coli, in particular, are estimated to cause more than 600 million cases of diarrhea annually and 700,000 deaths in children younger than 5 years.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Symptoms of bacterial infection may be subtle and nonspecific in infants and young children. Even in older children, symptoms may resemble those of common viral illnesses, leading to missed or delayed diagnosis. A thorough history, including any history of a prior UTI, and thoughtful analysis of the information provided is essential. Pertinent details can guide further diagnostic investigation.

• Neonates and infants with UTI, bacteremia, or sepsis may present with the following symptoms:
• • Fever
  • Hypothermia
  • Jaundice
  • Respiratory distress
  • Apnea
  • Poor feeding
  • Vomiting
  • Diarrhea
  • Fussiness
  • Irritability
  • Lethargy
• Particularly in young infants, meningitis may be present without overt signs attributable to the CNS.
• Infants with histories of prematurity, low birth weight, difficult or prolonged labor, intrapartum maternal fever, or antibiotic administration may have higher risk for serious bacterial infection.
• Older children with bacterial enteritis or UTI may have fever, vomiting, abdominal pain, or diarrhea with or without blood or mucus. In young children with UTI, urinary symptoms (eg, frequency, urgency, dysuria) vary and often are not present; daytime urinary incontinence or new onset of bedwetting may be more suggestive of UTI. Always consider UTI in the differential diagnosis of fever without apparent source. Constipation is not a symptom of UTI, but instead is associated with incomplete voiding and urinary stasis. Constipation may predispose a child to UTI and complicate treatment. In children with recurrent UTI, aggressive treatment of constipation may reduce subsequent UTIs.
• In cases of diarrheal illness, determine stool frequency (ie, number of stools or diaper changes in past 12-24 h), appearance (eg, loose, watery), and presence of blood or mucus. Inquire about a history of exposure to a child with bloody diarrhea or a known local outbreak of hemorrhagic colitis. Specific quantification of stool number and character is important because parents often describe a single loose stool as diarrhea. Also, remember various substances (eg, Kool-Aid, other foods containing red dyes) may tint stools red. Guaiac testing confirms the presence of blood.
• Evaluate the ability of patients who are vomiting or at risk of dehydration to take and tolerate fluids orally. Assess frequency of urination (ie, last void or wet diaper, number of voids in past 8-24 h).
• If the patient is experiencing abdominal pain, assess pain for the following features:
• • Severity and character (eg, sharp, dull, cramplike)
  • Location
  • Radiation
  • Duration
  • Nature (eg, constant, intermittent)
  • Aggravating and relieving factors

Physical

The child's overall appearance and behaviors (eg, alert, playful, fussy but consolable, lethargic, irritable, toxic) are valuable because these factors may direct diagnostic and therapeutic choices and influence decisions regarding outpatient management or admission.

• Among the aspects of general appearance to consider are alertness, activity, tone, age-appropriate interaction, and whether the child can be consoled. Observe, for example, whether the child explores the room, clings to the parent, or lies still on the table.
• Evidence of dehydration may be present in patients with bacterial enteritis. Ill appearance, tachycardia, and dry mucous membranes suggest significant volume depletion. Fontanelle and/or eyes may be sunken, but skin turgor change is a late finding and often not present. If previous weight is known, documented weight loss can help approximate the degree of dehydration.
• Assess peripheral perfusion by observing for extremity mottling, coolness, or delayed capillary refill. Evaluate the quality of central and peripheral pulses.
• Patients may have abdominal pain from either bacterial enteritis or a UTI. Flank pain or costovertebral angle tenderness suggests pyelonephritis. Abdominal pain sometimes is sufficiently severe to mimic appendicitis. Examine the abdomen for distention, increased or decreased bowel sounds, diffuse or localized tenderness, and signs of acute abdomen (eg, rigidity, rebound, guarding).
• Examine anogenital region in children who have urinary or abdominal symptoms or a history of bloody stools. Examination may reveal vulvovaginitis, perianal excoriation, or anal fissures.
• Complete examination should include adequate visualization of all skin surfaces. Subtle findings, such as petechiae or bruising, may be overlooked if the examination is rushed or limited.

Causes

• Diarrheal illnesses of various types may be associated with different E coli subtypes.
• • Enterotoxigenic E coli (ETEC) is the primary cause of traveler's diarrhea and the major cause of infantile diarrhea in less affluent countries. This diarrhea is watery and ranges from mild to severe. ETEC is widespread in areas with poor sanitation and is a ubiquitous contaminant of food and water sources.
    • Immunity develops to ETEC surface antigens, confining most disease to immunologically naïve travelers and weaning infants.
    • The pathogenesis of ETEC diarrhea relates to enterotoxin production, which gives rise to a secretory diarrhea. These toxins are divided into 2 groups, heat labile toxins (LTs) and heat stable toxins (STs). LTs are closely related in structure and function to the enterotoxin expressed by Vibrio cholerae.
    • ETEC's incubation period is 1-3 days, followed by the sudden onset of watery diarrhea without blood, mucus, or fecal leukocytes. Vomiting may occur, but most patients have no fever. Infection usually is self-limited and persists less than 5 days.
    • The Centers for Disease Control and Prevention's Traveler's Health web site provides additional information to physicians and the public.
  • Enterohemorrhagic E coli (EHEC) causes watery diarrhea and can elaborate Shigalike toxins and cause 2 distinctive syndromes: hemorrhagic colitis and HUS. The toxin is responsible for the systemic sequelae of the infection.
    • EHEC is an emerging cause of food-borne illness, particularly in the northern United States and Canada. Recent highly publicized outbreaks of HUS that caused fatalities have focused public attention on food safety.
    • Cattle are the primary reservoir of the EHEC strains that produce diarrhea in humans. Because EHEC is a common inhabitant of the bovine intestine, it may contaminate beef products or foods that contact bovine-exposed soil. Sources identified in outbreaks include ground beef, apple juice, and alfalfa sprouts, as well as fecally contaminated drinking water and swimming pools. Most outbreaks have been linked to 0157:H7 strains, although other serotypes have been implicated.
    • EHEC disease ranges from mild watery diarrhea to severe hemorrhagic colitis and may be followed by HUS in 10-15% of pediatric patients. Following an incubation period of 1-5 days, watery diarrhea develops, often accompanied by abdominal cramping and vomiting. Diarrhea becomes bloody in 1-2 days in most patients but usually is not associated with fecal leukocytes. Fever is present in about a third of cases. Illness duration typically is 4-10 days.
  • Of particular concern in pediatric populations, E coli 0157:H7 requires a relatively small inoculum for infection and spreads easily from child to child by the fecal-oral route.
  • HUS consists of the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal insufficiency. HUS typically develops in the second week of illness (range 2-14 d), often after the diarrhea has resolved. EHEC isolation from stool may be impossible by the time HUS has developed. Patients present with pallor, weakness, irritability, and oliguria or anuria. Treatment is supportive and includes management of fluid and electrolyte status and dialysis, if necessary. Chronic renal failure develops in as many as 10% of patients with HUS, and HUS kills 3-5% of affected patients.
  • Enteroinvasive E coli (EIEC), similar to Shigella species, can invade intestinal epithelial cells and causes watery diarrhea, dysentery, fever, vomiting, painful abdominal cramps, and tenesmus. Stools often contain blood and leukocytes. EIEC penetrate and proliferate within intestinal epithelial cells, eventually leading to colonic epithelial cell death. Invasiveness derives from a virulence plasmid closely related to that possessed by shigellae.
• Enteropathogenic E coli (EPEC), enteroaggregative E coli (EAEC), and diffusely adherent E coli (DAEC) cause watery diarrhea and dysentery. These occur most often in developing countries.
  • EPEC primarily affects infants and children. The resultant acute watery diarrhea may cause dehydration or become chronic and lead to failure to thrive.
  • EPEC has been associated with outbreaks of diarrhea in newborn nurseries in the United States, primarily in the 1950s and 1960s.
  • EAEC and DAEC are similar in geographic distribution, mechanism and effect to EPEC. Little data are available regarding their mechanisms of pathogenicity.
• UTIs
• • E coli is the most commonly isolated pathogen in pediatric UTIs. Virulence factors, such as pili, contribute to the pathogenicity of UTIs.
  • HUS has been reported following UTIs with enterohemorrhagic serotypes of E coli in patients who did not have a diarrheal illness.
• Neonatal infections
• • E coli infection in neonates may manifest as bacteremia, sepsis, UTI, or meningitis; it rarely manifests as pneumonia, soft tissue, or bone infection.
  • E coli strains with the K1 capsular polysaccharide antigen cause approximately 40% of the septicemia cases and 75% of the meningitis cases attributed to E coli.
• The usual source of E coli in neonatal infections is the maternal GI tract. The organism also may be acquired nosocomially, particularly in infants who are premature or who require mechanical ventilation.
• Predisposing factors include maternal perinatal infection, low birth weight, prolonged rupture of membranes, and traumatic delivery. Fetal hypoxia and skin or mucosal defects also increase the risk of gram-negative infection. Infants with galactosemia appear to have an increased susceptibility to serious bacterial infection, particularly E coli sepsis.
• In intensive care nurseries, mechanical ventilation, invasive procedures, indwelling catheters, and the frequent use of antimicrobial agents allow selection and proliferation of resistant strains of pathogenic gram-negative bacilli.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Yersinia enterocolitica infection
Clostridium difficile colitis
GI bleeding

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Culture stools in all patients with bloody diarrhea for pathogenic E coli, primarily the 0157:H7 serotype. If exposure is suspected (ie, as in the case of a known outbreak), assay even watery stools without blood for these pathogens.
• Routine stool cultures generally screen for Salmonella, Shigella and Campylobacter species. Because E coli organisms are normal fecal flora, laboratories must be advised specifically to assay for pathogenic E coli when a sample is submitted. Most 0157:H7 isolates do not ferment sorbitol; therefore, cultivation of specimens on sorbitol MacConkey medium is a convenient method for detection. Confirmation requires identification of presumptive isolates with specific antiserum.
• Detection of shiga-toxin–producing E coli in contaminated food or a patient's stool specimens may present a diagnostic challenge because of low copy numbers in the sample. Recently, more sensitive nucleic acid amplification methods, such as polymerase chain reaction (PCR) assays, have been developed for rapid identification of this organism directly from clinical specimens. Multiplex PCR assays for detection of all categories of diarrheagenic E coli are also available.
• Rapid enzyme immunoassays (nonculture tests) for E coli 0157:H7 have been developed but are not yet widely used clinically. Such tests may be available at large university hospitals or through reference laboratories. Stool culture remains the diagnostic criterion standard.
• ETEC diarrhea (traveler's diarrhea) primarily is diagnosed by clinical history, and treatment is initiated empirically. Laboratory assays involve detection of the associated enterotoxin, usually by enzyme immunoassay, and are not widely available.
• Fecal leukocyte presence varies but is more likely with EIEC. Stool guaiac testing may reveal occult blood. Test the stools of infants and toddlers with profuse watery diarrhea for rotavirus antigen, especially during fall and winter.
• Other laboratory findings associated with bacterial enteritis are nonspecific. Electrolyte changes may reflect fluid loss, and blood counts generally show an elevated leukocyte count with left shift.
• • Accurate UTI diagnosis requires an appropriately collected urine specimen. A clean-catch specimen is acceptable if the child is able to provide it. If not, urethral catheterization or suprapubic bladder aspiration is necessary.
  • Externally collected bag urine specimens are unsuitable for accurate diagnosis of pediatric UTI, and use of this collection technique is strongly discouraged.
• Externally collected urine samples are likely to be contaminated with skin or rectal flora, rendering them unreliable and their cultures uninterpretable.
• • Urinalysis results help make the decision whether to begin antibiotic treatment.
  • Urinary nitrite and leukocyte esterase are specific but poorly sensitive assays for UTI.
  • Pyuria strongly suggests a UTI, but may be absent even when infection exists.
• Perform a urine culture despite negative urinalysis results, particularly in infants and children younger than 3 years.
• All neonates with suspected sepsis should have specimens of blood, urine, and cerebrospinal fluid sent for culture and Gram stain prior to initiating antimicrobial therapy.

Imaging Studies

• Abdominal radiography is not necessarily indicated. Consider flat and upright views when the differential includes appendicitis or obstruction, including constipation.
• An air-contrast enema is both diagnostic and therapeutic for patients with a suspected intussusception.
• All children with a documented UTI should have imaging studies of the urinary tract to exclude an anatomic abnormality or vesicoureteral reflux. Renal ultrasound and voiding cystourethrogram are the currently recommended tests. Schedule both tests promptly. Girls older than 10 years with their first UTI may not require such extensive workup.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Treatment of bacterial gastroenteritis is primarily supportive and directed toward maintaining hydration and electrolyte balance. Do not administer antimotility agents. Antibiotic therapy rarely is indicated and should be deferred until culture results are available. Presumptive therapy should not be instituted due to the potential risks associated with antibiotic treatment for diarrhea caused by E coli 0157:H7. Treat UTIs and neonatal sepsis with appropriate antibiotic therapy and provide supportive care as indicated.

• Oral rehydration therapy (ORT) is the preferred treatment for fluid and electrolyte losses caused by diarrhea in children with mild-to-moderate dehydration. Intravenous hydration often is administered for severe dehydration or when vomiting prevents ORT. In most cases, even children who are vomiting can tolerate oral fluids if administered frequently in small amounts.
• Do not use antidiarrheal agents to treat acute diarrhea in pediatric patients. Antidiarrheal agents may prolong the clinical and bacteriologic course of disease and may be associated with other unacceptable morbidities such as excessive sedation. A retrospective study reported HUS was more likely to develop in patients with E coli 0157:H7 infection who received antimotility agents.
• Avoid antibiotic treatment of E coli 0157:H7 colitis. Available data indicate antimicrobials offer no substantial benefit and may be detrimental. Recent data suggest HUS is more likely to develop in patients treated with an antimicrobial agent.
• In a randomized controlled trial of antimicrobial therapy, administering trimethoprim-sulfamethoxazole (TMP-SMX) had no significant effect on HUS incidence, GI symptom duration, or organism excretion. A more recently published study of children with diarrhea due to E coli 0157:H7 showed antibiotic treatment significantly increased the risk of HUS development. In vitro studies have shown subinhibitory antibiotic concentrations can increase toxin production.
• Administer intravenous antibiotics to children who have evidence of systemic infection (eg, bacteremia, sepsis). Include a combination of ampicillin and an aminoglycoside in the initial empiric treatment of a neonate with suspected sepsis. Alternative regimens of ampicillin and a cephalosporin, such as cefotaxime, also are acceptable. Coverage may be narrowed when the etiologic agent and its antimicrobial susceptibilities have been determined. Base therapy duration on the patient's response and established treatment guidelines (usually 10-14 d for uncomplicated sepsis, >21 d for meningitis).
• UTIs may be treated with oral antibiotics if the child can tolerate oral medication without vomiting. Antibiotic regimens of 3 days are inadequate; continue treatment for 10 days.

Consultations

• In cases of hemorrhagic colitis, consultation with a pediatric infectious disease specialist is recommended, especially if considering antibiotic therapy.
• When HUS is suspected or confirmed, a pediatric nephrologist should assist with patient management because dialysis may be necessary. Early dialysis is associated with improved outcome.
• Ongoing research protocols investigating the benefit of a toxin-adsorbing preparation appear promising. Enrollment in such a treatment study may be an option at selected tertiary care settings.

Diet

Children who have diarrhea should continue to receive age-appropriate diets. Feed dehydrated children as soon as they have been rehydrated. Feeding may be withheld briefly for children who are vomiting, but prolonged periods of fasting or specialized diets are unnecessary once vomiting ceases.

Activity

• Increase allowable activities, as tolerated, for all affected children. In general, children eagerly resume vigorous activity as their illness resolves and restrictions are unnecessary.
• Children with E coli 0157:H7 infection should not return to group childcare settings until the diarrhea has resolved and 2 stool culture results are negative.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Antibiotic therapy is not indicated in most cases of E coli enteritis; guidelines for specific circumstances are outlined below.

Antimotility agents are contraindicated for all cases of pediatric gastroenteritis.

UTIs may be treated with a variety of oral antibiotics, most commonly trimethoprim and sulfamethoxazole, amoxicillin, or cefixime. Duration of therapy is 10 days.

Neonatal sepsis and meningitis are treated based on identified organism sensitivities and clinical response.

Drug Category: Antibiotics

Treatment of traveler's diarrhea rarely is necessary. Prophylaxis for traveler's diarrhea with medications (eg, bismuth subsalicylate, trimethoprim and sulfamethoxazole) is not recommended for children because of potential salicylate accumulation and allergic reactions. Efficacy of antibiotic treatment of EIEC and EHEC is not established. Data suggest treating EHEC does not alter the course of infection and increases risk of subsequent HUS. UTI in infants and children is treated for 10 days because of the difficulty distinguishing between uncomplicated cystitis and pyelonephritis.

Drug Name	Amoxicillin (Amoxil, Biomox, Trimox)
Description	Reasonable choice to treat pediatric UTI. Liquid preparation is palatable and well tolerated. It is concentrated in the urine and active against most gram-positive and some gram-negative organisms.
Adult Dose	250-500 mg PO tid for 3-7 d
Pediatric Dose	30-50 mg/kg/d PO divided tid for 10 d
Contraindications	Documented hypersensitivity
Interactions	Reduces efficacy of oral contraceptives
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Use with caution in patients who are allergic to cephalosporins; adjust dose in renal impairment

Drug Name	Cefixime (Suprax)
Description	Third-generation cephalosporin is a second-line choice to treat UTI or traveler's diarrhea; liquid preparation is pleasant tasting.
Adult Dose	400 mg/d PO divided bid
Pediatric Dose	UTI: 8 mg/kg/d PO divided bid for 10 d ETEC (traveler's diarrhea): 8 mg/kg/d PO divided bid for 3-5 d
Contraindications	Documented hypersensitivity
Interactions	Coadministration of aminoglycosides increase nephrotoxicity; probenecid may increase effects
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Use with caution in patients with penicillin allergy; adjust dose in renal impairment

Drug Name	Ampicillin (Marcillin, Omnipen, Polycillin, Principen, Totacillin)
Description	Administer parenterally in combination with an aminoglycoside or cephalosporin in cases of neonatal sepsis or meningitis; oral preparation is a second-line therapy for traveler's diarrhea and dysentery.
Adult Dose	250-500 mg PO qid 500 mg to 3 g IV q4-6h; not to exceed 12 g/d
Pediatric Dose	ETEC (traveler's diarrhea), EIEC (dysentery): 100 mg/kg/d PO divided qid for 5 d Neonatal sepsis and meningitis: 100-200 mg/kg/d IV/IM divided qid for 10-21 d
Contraindications	Documented hypersensitivity
Interactions	Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction; use with caution in patients who are allergic to cephalosporins

Drug Name	Gentamicin (Garamycin, Gentacidin)
Description	Aminoglycoside antibiotic used in combination with ampicillin to treat neonatal sepsis and meningitis; provides gram-negative coverage and works synergistically against gram-positives.
Adult Dose	3-6 mg/kg/d IV divided tid
Pediatric Dose	<5 years: 2.5 mg/kg/dose IV/IM q8h >5 years: 1.5-2.5 mg/kg/dose IV/IM q8h or 6-7.5 mg/kg/d divided q8h; not to exceed 300 mg/d; monitor as in adults
Contraindications	Documented hypersensitivity
Interactions	Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents, possibly prolonging respiratory depression; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Pregnancy	D - Unsafe in pregnancy
Precautions	Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment; monitor serum levels to minimize risk of toxicity and optimize therapy; nephrotoxicity and ototoxicity may be associated with prolonged elevated trough concentrations

Drug Name	Cefotaxime (Claforan)
Description	Third-generation cephalosporin administered parenterally in combination with ampicillin to treat neonatal sepsis or meningitis.
Adult Dose	1-2 g IV/IM q4-12h
Pediatric Dose	150-250 mg/kg/d IV/IM divided bid/tid for 10-21 d
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment; caution in women who are breastfeeding and in patients who are allergic to penicillin

Drug Name	Ciprofloxacin (Cipro, Ciloxan)
Description	Quinolone antibiotics are an alternative therapy for adult UTI or bacterial enteritis. Use is contraindicated in pediatric patients when an acceptable alternative is available.
Adult Dose	ETEC (traveler's diarrhea), EIEC (dysentery): 500 mg PO bid for 3 d UTI: 250-500 mg PO bid for 3 d
Pediatric Dose	ETEC, EIEC: 20-30 mg/kg/d PO divided bid for 1-3 d
Contraindications	Documented hypersensitivity
Interactions	Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Use with caution in children <18 y; in prolonged therapy, periodically evaluate organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

Drug Name	Rifaximin (Xifaxan, RedActiv, Flonorm)
Description	Nonabsorbed ( <0.4%), broad-spectrum antibiotic specific for enteric pathogens of the gastrointestinal tract (ie, gram-positive, gram-negative, aerobic and anaerobic). Rifampin structural analog. Binds to beta-subunit of bacterial DNA-dependent RNA polymerase, thereby inhibiting RNA synthesis. Indicated for E coli (enterotoxigenic and enteroaggregative strains) associated with traveler's diarrhea.
Adult Dose	200 mg PO tid
Pediatric Dose	<12 years: Not established >12 years: Administer as in adults
Contraindications	Documented hypersensitivity to rifaximin or rifamycin antimicrobial agents (eg, rifampin)
Interactions	Induces CYP450 3A4 in vitro; limited data exist; no significant interactions shown in single dose studies with midazolam and oral contraceptives
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	May promote intestinal bacterial overgrowth and cause superinfection; discontinue if diarrhea persists more than 24-48 h or worsens; seek immediate medical care if fever and/or bloody stools emerge (tablets not effective); not effective for traveler's diarrhea due to suspected pathogens other than E coli; postmarketing reports include allergic dermatitis, rash, angioneurotic edema, urticaria, and pruritus

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Admit for fluid resuscitation and intravenous antibiotic administration any child who is significantly dehydrated, is persistently vomiting, or who has evidence of pyelonephritis.
• Children with suspected or confirmed sepsis, meningitis, or HUS require skilled inpatient management. HUS may progress to renal failure, which requires meticulous fluid electrolyte management and may require dialysis.

Transfer

• Arrange transfer to a tertiary care facility if HUS is suspected. These patients may require dialysis and should be managed by a team that includes a pediatric intensivist, nephrologist, and infectious disease specialist.

Deterrence/Prevention

• Traveler's diarrhea
• • Drink only carbonated beverages and boiled or bottled water (preferably carbonated). Consider bringing supply of bottled water or premixed infant formula.
  • Travelers should avoid ice, raw salads, and any fruits they do not peel themselves. Consume foods while they are steaming hot.
  • Prophylactic antibiotic treatment is not recommended for infants and children. Parents should carry packets of oral rehydration salts when traveling outside the United States.
• Thoroughly cooking ground beef is the most effective measure to prevent hemorrhagic colitis caused by E coli 0157:H7.

Patient Education

• Advise parents of children diagnosed with hemorrhagic colitis to observe their child closely for signs of HUS (eg, oliguria or anuria, pallor, irritability).
• Make parents of children diagnosed with UTI aware of the possibility that UTI may be the cause of future episodes of fever, particularly fever without apparent source. Parents should be reminded to inform treating physicians of the child's history of UTI and to discuss indications for obtaining a urine culture.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to consider and investigate E coli 0157:H7 in the differential diagnosis of bloody diarrhea (Most laboratories do not assay for pathogenic E coli without specific instruction.)
• Failure to recognize and diagnose HUS and to obtain appropriate subspecialist consultations
• Failure to follow up diagnosis of UTI with appropriate imaging studies because an undiagnosed anatomic abnormality or vesicoureteral reflux can lead to renal scarring and eventually progress to renal insufficiency or failure

Special Concerns

• Always consider a UTI in infants and young children who present with fever without an apparent source.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Amieva MR. Important bacterial gastrointestinal pathogens in children: a pathogenesis perspective. Pediatr Clin North Am. 2005;52:749-77. [Medline].
• Blackall DP, Marques MB. Hemolytic uremic syndrome revisited: Shiga toxin, factor H, and fibrin generation. Am J Clin Pathol. Jun 2004;121 Suppl:S81-8. [Medline].
• Bower JR. Foodborne diseases: Shiga toxin producing E. coli (STEC). Pediatr Infect Dis J. Oct 1999;18(10):909-10. [Medline].
• David RD, DeBlieux PM, Press R. Rational antibiotic treatment of outpatient genitourinary infections in a changing environment. Am J Med. 2005;118 Suppl 7A:7S-13S. [Medline].
• Emmerson AM, Hawkey PM, Gillespie SH. Principles and Practice of Clinical Bacteriology. John Wiley & Sons;1997:373-88.
• Hostetter MK. Epidemiology of travel-related morbidity and mortality in children. Pediatr Rev. Jul 1999;20(7):228-33. [Medline].
• Igarashi T, Inatomi J, Wake A, et al. Failure of pre-diarrheal antibiotics to prevent hemolytic uremic syndrome in serologically proven Escherichia coli O157:H7 gastrointestinal infection. J Pediatr. Dec 1999;135(6):768-9. [Medline].
• Johnson CE. New advances in childhood urinary tract infections. Pediatr Rev. Oct 1999;20(10):335-42; quiz 343. [Medline].
• Levy HL, Sepe SJ, Shih VE, et al. Sepsis due to Escherichia coli in neonates with galactosemia. N Engl J Med. Oct 13 1977;297(15):823-5. [Medline].
• Li F, Zhao C, Zhang W, et al. Use of ramification amplification assay for detection of Escherichia coli 0157:H7 and E. coli Shiga toxin-producing strains. J Clin Microbiol. 2005;43:6086-90. [Medline]. [Full Text].
• Loening-Baucke V. Urinary incontinence and urinary tract infection and their resolution with treatment of chronic constipation of childhood. Pediatrics. Aug 1997;100(2 Pt 1):228-32. [Medline].
• McMillan JA , ed. Diarrheagenic escherichia coli. In: Oski's Pediatrics: Principles and Practice. 3rd ed. Lippincott Williams & Wilkins;1999:964-9.
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Article Last Updated: Jul 26, 2006