eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Escherichia Coli Infections

Archana Chatterjee, MD, PhD, Professor of Pediatrics, Medical Microbiology and Immunology, and Pharmacy, Division of Pediatric Infectious Diseases, Chief of Division of Pediatric Infectious Diseases, Creighton University School of Medicine; Hospital Epidemiologist and Medical Director of Infection Control, Children's Hospital
Catherine O'Keefe, DNP, APRN, Assistant Professor of Nursing, Pediatric Nurse Practitioner, Pediatric Infectious Diseases, Creighton University School of Nursing; Sara L Cuthill, MD, Fellow, Developmental and Behavioral Pediatrics, Departmental and Behavioral Pediatrics, Interstate Medical Office East; Meera Varman, MD, Assistant Professor, Department of Pediatrics, Section of Pediatric Infectious Diseases, Creighton University School of Medicine

Updated: Jan 8, 2009

Introduction

Background

Escherichia coli, a facultatively anaerobic gram-negative bacillus, is a major component of the normal intestinal flora and is 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 is also a commonly identified cause of urinary tract infections (UTIs), as well as neonatal sepsis and meningitis.

Uropathogenic E coli (UPEC) has the ability to colonize the uroepithelium by means of surface fimbriae. Although only partially understood, UPEC has been suggested to cause either direct cellular damage or direct invasion of the renal epithelial cells.¹

Five pathotypes have of diarrheagenic E coli have been recognized; each pathotype has a distinct pathogenesis. The pathotypes are as follows:

• Enterotoxigenic E coli (ETEC)
• Enterohemorrhagic E coli (EHEC)
• Enteropathogenic E coli (EPEC)
• Enteroinvasive E coli (EIEC)
• Enteroaggregative E coli (EAEC)

Frequency

United States

Statistics on pathogenic E coli strains reflect increasing recognition and surveillance over the past 2 decades. According to the Foodborne Diseases Active Surveillance Network (FoodNet) of the Centers for Disease Control and Prevention (CDC) Emerging Infections Program, in 2007, the incidence of Shiga-toxin–producing E coli (O157) was 1.20 cases per 100,000 population, and the incidence of Shiga-toxin–producing E coli (non-O157) was 0.57 cases per 100,000 population). Since the beginning of surveillance in 1996, the incidence of Shiga-toxin–producing E coli (O157) has decreased 25%.³

International

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

ETEC is the most common enteropathogen in developing countries, accounting for approximately 210 million diarrhea episodes and approximately 380,000 deaths.^4,5 Traveler’s diarrhea is primarily caused by ETEC; thus, persons traveling to endemic areas regularly import the pathogen to the developed world.^6,7,8  

Mortality/Morbidity

Several E coli pathotypes have been implicated in chronic diarrhea among severely immunocompromised patients (eg, patients with human immunodeficiency virus [HIV]).^9,10,11  ETEC causes more dehydrating diarrhea cases among infants in developing countries than any other pathotype.^12,13

Age

People of any age can become infected. Very young individuals and the elderly are the most likely groups to become seriously ill and to develop HUS.

Clinical

History

Symptoms of Escherichia coli 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 urinary tract infection (UTI), and thoughtful analysis of the information provided is essential. Pertinent details can guide further diagnostic investigation.

• Neonates and infants with UTIs, 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 are often 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 is instead associated with incomplete voiding and urinary stasis. Constipation may predispose a child to UTI and may 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.
  • Enterotoxigenic E coli (ETEC) diarrhea is watery without blood, mucous, or fecal leukocytes and ranges from mild to severe.
  • Enterohemorrhagic E coli (EHEC) disease ranges from mild watery diarrhea to severe hemorrhagic colitis, often accompanied by abdominal cramping and vomiting. Diarrhea becomes bloody in 1-2 days in most patients but is usually not associated with fecal leukocytes. Fever is present in about a third of cases.
  • Enteroinvasive E coli (EIEC) causes watery diarrhea, dysentery, fever, vomiting, painful abdominal cramps, and tenesmus. Stools often contain blood and leukocytes.
  • Enteropathogenic E coli (EPEC) and Enteroaggregative E coli (EAEC) cause watery diarrhea and dysentery. The resultant acute watery diarrhea may cause dehydration or become chronic and lead to failure to thrive.
• 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). Vomiting may occur with ETEC.
• 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 is 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

• ETEC infection: ETEC is the primary cause of traveler's diarrhea and the major cause of infantile diarrhea in less affluent countries. ETEC is widespread in areas with poor sanitation and is a ubiquitous contaminant of food and water sources. ETEC's incubation period is 1-3 days. Infection usually is self-limited and persists less than 5 days.
• EHEC infection
  • EHEC is an emerging cause of food-borne illness, particularly in the northern United States and Canada.
  • Recent highly publicized outbreaks of hemolytic-uremic syndrome (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.^14,9,15,16
  • 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. The incubation period of EHEC is 1-5 days, with illness duration typically 4-10 days.
  • HUS develops in 10-15% of pediatric patients. Chronic renal failure develops in as many as 10% of patients with HUS, and HUS kills 3-5% of affected patients.¹⁷  
• EPEC infection: EPEC is most often found in developing countries, primarily affecting infants and children. EPEC has been associated with outbreaks of diarrhea in newborn nurseries in the United States, primarily in the 1950s and 1960s.
• EAEC infection: EAEC is similar in geographic distribution, mechanism, and effect to EPEC. The CDC's Traveler's Health Web site provides additional information to physicians and the public. 
• 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 80% 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.

Differential Diagnoses

Other Problems to Be Considered

Yersinia enterocolitica infection
Clostridium difficile colitis
GI bleeding

Workup

Laboratory Studies

• Culture stools in all patients with bloody diarrhea for pathogenic Escherichia 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. Enterohemorrhagic E coli (EHEC) isolation from stool may be impossible by the time hemolytic-uremic syndrome (HUS) has developed; thus, when EHEC is suspected, a stool culture should be obtained as early in the illness as possible (eg, within the first week).
• 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 O and H 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.^2,18
• Rapid enzyme immunoassays (nonculture tests) for E coli 0157:H7 have been developed.¹⁹ Such tests may be available at large university hospitals or through reference laboratories. Stool culture remains the diagnostic criterion standard.
• Enterotoxigenic E coli (ETEC) diarrhea (traveler's diarrhea) is primarily diagnosed by clinical history, and treatment is empirically initiated. Laboratory assays involve detection of the associated enterotoxin, usually by enzyme immunoassay, and are not widely available.²⁰
• Fecal leukocyte presence varies but is more likely with enteroinvasive E coli (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 CBC counts generally reveal an elevated leukocyte count with left shift.
• Accurate urinary tract infection (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 is present.
• 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 diagnosis includes appendicitis or obstruction, including constipation. A CT scan of the abdomen with contrast is more sensitive than plain radiography for detection of E coli– induced colitis.²¹
• 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 ultrasonography and voiding cystourethrography are the currently recommended tests. Schedule both tests promptly. Girls older than 10 years with their first UTI may not require such extensive evaluation.

Treatment

Medical Care

Treatment of bacterial gastroenteritis is primarily supportive and directed toward maintaining hydration and electrolyte balance. Antibiotic therapy is rarely indicated and should be deferred until culture results are available.

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 is often 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.²²

• Do not use antimotility agents to treat acute diarrhea in pediatric patients. Antimotility agents may prolong the clinical and bacteriologic course of the disease and may be associated with other unacceptable morbidities such as excessive sedation. A retrospective study reported hemolytic-uremic syndrome (HUS) was more likely to develop in patients with E coli 0157:H7 infection who received antimotility agents.²³
• Antibiotic treatment of E coli 0157:H7 colitis is controversial. Early data indicated antimicrobials offer no substantial benefit and may increase the risk of developing HUS.²³ In vitro studies have shown subinhibitory antibiotic concentrations can increase toxin production.²⁴ However, a subsequent meta-analysis reported no association between the use of antimicrobials and higher risk of HUS.²⁵  In the absence of conclusive evidence, empiric antibiotics should not be administered due to the potential risk of HUS.²  
• 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, are also 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).²
• Urinary tract infections (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.
• Treatment of HUS is supportive and includes management of fluid and electrolyte status and dialysis, if necessary. Ake et al (2005) propose that early volume expansion with parenteral isotonic fluids during the pre-HUS interval is essential to attenuate renal injury associated with HUS.²⁶  Leukocytosis has been identified as an early predictor of the development of HUS following an E coli O157:H7 infection.^27,28

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.²⁴ 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

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

Antimotility agents are contraindicated for all cases of pediatric gastroenteritis.

Urinary tract infections (UTIs) may be treated with various 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 susceptibility and clinical response.

Antibiotics

Treatment of traveler's diarrhea is rarely 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 enteroinvasive E coli (EIEC) and enterohemorrhagic E coli (EHEC) is not established. Data suggest treating EHEC does not alter the course of infection and increases risk of subsequent hemolytic-uremic syndrome (HUS). UTI in infants and children is treated for 10 days because of the difficulty distinguishing between uncomplicated cystitis and pyelonephritis.

Sulfamethoxazole and Trimethoprim (Bactrim, Cotrim, Septra)

First-line therapy for UTI and most E coli diarrheal illness; resistant organisms are fairly common.

Dosing

Adult

160 mg (trimethoprim component)/800 mg (sulfamethoxazole component) PO q12h for 3 d (ie, 1 double-strength tab PO q12h)

Pediatric

ETEC (traveler's diarrhea): 10 mg/kg/d PO divided bid for 3 d
UTI: 10 mg/kg/d PO divided bid for 10 d
EIEC (dysentery): 10 mg/kg/d PO divided bid for 5 d
Note: Doses based on trimethoprim component

Interactions

May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenic purpura in elderly; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine

Contraindications

Documented hypersensitivity; megaloblastic anemia due to folate deficiency; age <2 mo

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not use near term in pregnancy (risk of kernicterus in newborn); discontinue at first appearance of skin rash or sign of adverse reaction; frequently obtain CBC counts; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; caution in folate deficiency; hemolysis may occur in G-6-PD deficiency; patients with AIDS may not tolerate or respond; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); administer fluids to prevent crystalluria and stone formation

Amoxicillin (Amoxil, Biomox, Trimox)

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.

Dosing

Adult

250-500 mg PO tid for 3-7 d

Pediatric

30-50 mg/kg/d PO divided tid for 10 d

Interactions

Reduces efficacy of PO contraceptives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Use with caution in patients who are allergic to cephalosporins; adjust dose in renal impairment

Cefixime (Suprax)

Third-generation cephalosporin is a second-line choice to treat UTI or traveler's diarrhea; liquid preparation is pleasant tasting.

Dosing

Adult

400 mg/d PO divided bid

Pediatric

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

Interactions

Coadministration of aminoglycosides increase nephrotoxicity; probenecid may increase effects

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Use with caution in patients with penicillin allergy; adjust dose in renal impairment

Ampicillin (Marcillin, Omnipen, Polycillin, Principen, Totacillin)

Administer parenterally in combination with an aminoglycoside or cephalosporin in cases of neonatal sepsis or meningitis; PO preparation is a second-line therapy for traveler's diarrhea and dysentery.

Dosing

Adult

250-500 mg PO qid
500 mg to 3 g IV q4-6h; not to exceed 12 g/d

Pediatric

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

Interactions

Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases effects and has additive effects on ampicillin rash; may decrease effects of PO contraceptives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction; use with caution in patients who are allergic to cephalosporins

Gentamicin

Aminoglycoside antibiotic used in combination with ampicillin to treat neonatal sepsis and meningitis; provides gram-negative coverage and works synergistically against gram-positives.

Dosing

Adult

3-6 mg/kg/d IV divided tid

Pediatric

<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

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)

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

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

Cefotaxime (Claforan)

Third-generation cephalosporin administered parenterally in combination with ampicillin to treat neonatal sepsis or meningitis.

Dosing

Adult

1-2 g IV/IM q4-12h

Pediatric

150-250 mg/kg/d IV/IM divided bid/tid for 10-21 d

Interactions

Probenecid may increase levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal impairment; caution in women who are breastfeeding and in patients who are allergic to penicillin

Ciprofloxacin (Cipro, Ciloxan)

Quinolone antibiotics are an alternative therapy for adult UTI or bacterial enteritis. Use is contraindicated in pediatric patients when an acceptable alternative is available.

Dosing

Adult

ETEC (traveler's diarrhea), EIEC (dysentery): 500 mg PO bid for 3 d
UTI: 250-500 mg PO bid for 3 d

Pediatric

ETEC, EIEC: 20-30 mg/kg/d PO divided bid for 1-3 d

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)

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

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

Rifaximin (Xifaxan, RedActiv, Flonorm)

Nonabsorbed (<0.4%), broad-spectrum antibiotic specific for enteric pathogens of the GI 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.

Dosing

Adult

200 mg PO tid

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Interactions

Induces CYP450 3A4 in vitro; limited data exist; no significant interactions shown in single dose studies with midazolam and PO contraceptives

Contraindications

Documented hypersensitivity to rifaximin or rifamycin antimicrobial agents (eg, rifampin)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

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

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 hemolytic-uremic syndrome (HUS) require skilled inpatient management. HUS may progress to renal failure, which requires meticulous fluid electrolyte management and may require dialysis.

Further Outpatient Care

• Monitor patients with Escherichia coli infection for postinfectious functional GI disorders such as irritable bowel syndrome.²⁹

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.
  • Promising data have been reported in a patch vaccine containing heat-labile toxin from E coli.^30,31
• Thoroughly cooking ground beef is the most effective measure to prevent hemorrhagic colitis caused by E coli 0157:H7.
• Although an National Institutes of Health (NIH) investigational vaccine for E coli O157:H7 has been found to be immunogenic in young children, sporadic outbreaks could limit its use on a broad scale.³²  Priority has been placed on vaccination strategies to reduce the carriage of these organisms in the principal reservoir of this pathogen (ie, cattle).¹⁷

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 urinary tract infection (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

Medicolegal Pitfalls

• Failure to consider and investigate Escherichia 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 hemolytic-uremic syndrome (HUS) and to obtain appropriate subspecialist consultations
• Failure to follow up diagnosis of urinary tract infection (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

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2. Escherichia coli diarrhea. In: Pickering LK, Baker CJ, Overturf GD, Prober CG (Editors). American Academy of Pediatricians Report of the Committee on Infectious Diseases. Red Book. 2008:291-6.

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Keywords

Escherichia coli infections, E coli infections, Escherichia coli, E coli, colibacillus, diarrhea, diarrheal illness, hemolytic-uremic syndrome, HUS, urinary tract infection, UTI, neonatal sepsis, meningitis, enterotoxigenic E coli, ETEC, enterohemorrhagic E coli, EHEC, enteropathogenic E coli, EPEC, enteroinvasive E coli, EIEC, enteroaggregative E coli, EAEC, hemolytic anemia, thrombocytopenia, renal insufficiency, diarrhea, oliguria, anuria, traveler's diarrhea, bacteremia, sepsis, respiratory distress, prematurity, low birth weight, hemorrhagic colitis, abdominal cramping, dysentery

Contributor Information and Disclosures

Author

Archana Chatterjee, MD, PhD, Professor of Pediatrics, Medical Microbiology and Immunology, and Pharmacy, Division of Pediatric Infectious Diseases, Chief of Division of Pediatric Infectious Diseases, Creighton University School of Medicine; Hospital Epidemiologist and Medical Director of Infection Control, Children's Hospital
Archana Chatterjee, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Society for Microbiology, International Society for Infectious Diseases, Pediatric Infectious Diseases Society, and Society for Pediatric Research
Disclosure: GlaxosmithKline Honoraria Speaking and teaching; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; Sanofi-Pasteur Honoraria Speaking and teaching; Wyeth Honoraria Speaking and teaching; GlaxoSmithKline Grant/research funds Other; MedImmune  Other; Merck Grant/research funds Other; Novartis Grant/research funds Other; Sanofi-Pasteur Grant/research funds Other

Coauthor(s)

Catherine O'Keefe, DNP, APRN, Assistant Professor of Nursing, Pediatric Nurse Practitioner, Pediatric Infectious Diseases, Creighton University School of Nursing
Catherine O'Keefe, DNP, APRN is a member of the following medical societies: American Academy of Nurse Practitioners, National Association of Pediatric Nurse Practitioners, and Nebraska Nurse Practitioners
Disclosure: Nothing to disclose.

Sara L Cuthill, MD, Fellow, Developmental and Behavioral Pediatrics, Departmental and Behavioral Pediatrics, Interstate Medical Office East
Sara L Cuthill, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Meera Varman, MD, Assistant Professor, Department of Pediatrics, Section of Pediatric Infectious Diseases, Creighton University School of Medicine
Meera Varman, MD is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society
Disclosure: phamaceutical companies Honoraria Speaking and teaching; phamaceutical companies Grant/research funds clinical trials

Medical Editor

Ashir Kumar, MBBS, MD, FAAP, Professor, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University; Consulting Staff, Department of Pediatrics, EW Sparrow Hospital
Ashir Kumar, MBBS, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association of Physicians of Indian Origin, American Federation for Clinical Research, American Society for Microbiology, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Mark R Schleiss, MD, American Legion Chair of Pediatrics, Professor of Pediatrics, Division Director, Division of Infectious Diseases and Immunology, Department of Pediatrics, University of Minnesota School of Medicine
Mark R Schleiss, MD is a member of the following medical societies: American Pediatric Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Consulting; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching; sanofi pasteur Grant/research funds Unrestricted research grant; sanofi pasteur  Consulting; sanofi pasteur Honoraria Speaking and teaching; Tap Honoraria Speaking and teaching; Baxter Healthcare Honoraria Speaking and teaching

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

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