Clinical manifestations, diagnosis and treatment of enterohemorrhagic Escherichia coli (EHEC) infection
- Stephen B Calderwood, MD
Stephen B Calderwood, MD
- Editor-in-Chief — Infectious Diseases
- Section Editor — Bacterial Infections
- Professor of Medicine (Microbiology and Immunobiology)
- Harvard Medical School
- Section Editors
- Daniel J Sexton, MD
Daniel J Sexton, MD
- Editor-in-Chief — Infectious Diseases
- Section Editor — Bacterial Infections
- Professor of Medicine
- Duke University Medical Center
- Sheldon L Kaplan, MD
Sheldon L Kaplan, MD
- Editor-in-Chief — Pediatrics
- Section Editor — Pediatric Infectious Diseases
- Professor and Vice Chairman for Clinical Affairs
- Baylor College of Medicine
Enterohemorrhagic Escherichia coli (EHEC) are strains capable of producing Shiga toxin and typically cause bloody diarrhea [1-4]. Hemolytic-uremic syndrome (HUS) complicates 6 to 9 percent of EHEC infections overall, and about 15 percent of EHEC infections in children under age 10 [3,5,6]. Since the initial recognition of severe bloody diarrhea due to E. coli O157:H7 in the United States in 1982, outbreaks and sporadic infections have been attributed to EHEC worldwide [5-22]. In May 2011, a new Shiga toxin-producing EHEC strain, O104:H4, was identified as the cause of an outbreak in Germany and other countries in Europe [23,24].
The clinical manifestations, diagnosis, and treatment of EHEC will be reviewed here. The microbiology, pathogenesis, epidemiology, and prevention of EHEC infections are discussed separately. (See "Microbiology, pathogenesis, epidemiology, and prevention of enterohemorrhagic Escherichia coli (EHEC)".)
The incubation period between exposure to Enterohemorrhagic E. coli (EHEC) and the onset of symptoms is typically three to four days (range one to nine days) . Clinical manifestations may include history of bloody diarrhea, a visibly bloody stool specimen, no reported fever, a peripheral white blood cell count above 10,000/microL, and abdominal tenderness [3,11,25]. In one large series, three or more of these features were present in 65 percent of patients with E. coli O157:H7 infection (compared with 19 percent of those with infection due to Shigella, Campylobacter, or Salmonella) .
Hemolytic-uremic syndrome is a major complication of EHEC infection, discussed below. (See 'Hemolytic-uremic syndrome' below.)
Hospitalization is required in 23 to 47 percent of symptomatic patients with acute diarrhea due to EHEC, with a median hospital stay of 6 to 14 days [5,7,8]. The mortality rate is generally 1 to 2 percent, although it may be substantially higher among the elderly and among patients with HUS [5,26]. Uncomplicated EHEC infection generally resolves in approximately one week.
- Levine MM. Escherichia coli that cause diarrhea: enterotoxigenic, enteropathogenic, enteroinvasive, enterohemorrhagic, and enteroadherent. J Infect Dis 1987; 155:377.
- O'Brien AO, Lively TA, Chen ME, et al. Escherichia coli O157:H7 strains associated with haemorrhagic colitis in the United States produce a Shigella dysenteriae 1 (SHIGA) like cytotoxin. Lancet 1983; 1:702.
- Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 2005; 365:1073.
- Page AV, Liles WC. Enterohemorrhagic Escherichia coli Infections and the Hemolytic-Uremic Syndrome. Med Clin North Am 2013; 97:681.
- Boyce TG, Swerdlow DL, Griffin PM. Escherichia coli O157:H7 and the hemolytic-uremic syndrome. N Engl J Med 1995; 333:364.
- Bell BP, Goldoft M, Griffin PM, et al. A multistate outbreak of Escherichia coli O157:H7-associated bloody diarrhea and hemolytic uremic syndrome from hamburgers. The Washington experience. JAMA 1994; 272:1349.
- Su C, Brandt LJ. Escherichia coli O157:H7 infection in humans. Ann Intern Med 1995; 123:698.
- Waters JR, Sharp JC, Dev VJ. Infection caused by Escherichia coli O157:H7 in Alberta, Canada, and in Scotland: a five-year review, 1987-1991. Clin Infect Dis 1994; 19:834.
- Tarr PI. Escherichia coli O157:H7: clinical, diagnostic, and epidemiological aspects of human infection. Clin Infect Dis 1995; 20:1.
- Noël JM, Boedeker EC. Enterohemorrhagic Escherichia coli: a family of emerging pathogens. Dig Dis 1997; 15:67.
- Slutsker L, Ries AA, Greene KD, et al. Escherichia coli O157:H7 diarrhea in the United States: clinical and epidemiologic features. Ann Intern Med 1997; 126:505.
- Dundas S, Todd WT, Stewart AI, et al. The central Scotland Escherichia coli O157:H7 outbreak: risk factors for the hemolytic uremic syndrome and death among hospitalized patients. Clin Infect Dis 2001; 33:923.
- Slutsker L, Ries AA, Maloney K, et al. A nationwide case-control study of Escherichia coli O157:H7 infection in the United States. J Infect Dis 1998; 177:962.
- Jay MT, Garrett V, Mohle-Boetani JC, et al. A multistate outbreak of Escherichia coli O157:H7 infection linked to consumption of beef tacos at a fast-food restaurant chain. Clin Infect Dis 2004; 39:1.
- Cody SH, Glynn MK, Farrar JA, et al. An outbreak of Escherichia coli O157:H7 infection from unpasteurized commercial apple juice. Ann Intern Med 1999; 130:202.
- Fukushima H, Hashizume T, Morita Y, et al. Clinical experiences in Sakai City Hospital during the massive outbreak of enterohemorrhagic Escherichia coli O157 infections in Sakai City, 1996. Pediatr Int 1999; 41:213.
- Centers for Disease Control and Prevention (CDC). Escherichia coli O157:H7 infection associated with drinking raw milk--Washington and Oregon, November-December 2005. MMWR Morb Mortal Wkly Rep 2007; 56:165.
- Crump JA, Sulka AC, Langer AJ, et al. An outbreak of Escherichia coli O157:H7 infections among visitors to a dairy farm. N Engl J Med 2002; 347:555.
- Varma JK, Greene KD, Reller ME, et al. An outbreak of Escherichia coli O157 infection following exposure to a contaminated building. JAMA 2003; 290:2709.
- Bender JB, Hedberg CW, Besser JM, et al. Surveillance by molecular subtype for Escherichia coli O157:H7 infections in Minnesota by molecular subtyping. N Engl J Med 1997; 337:388.
- Elliott EJ, Robins-Browne RM, O'Loughlin EV, et al. Nationwide study of haemolytic uraemic syndrome: clinical, microbiological, and epidemiological features. Arch Dis Child 2001; 85:125.
- Centers for Disease Control and Prevention (CDC). Multistate outbreak of Escherichia coli O157:H7 infections associated with eating ground beef--United States, June-July 2002. MMWR Morb Mortal Wkly Rep 2002; 51:637.
- Frank C, Werber D, Cramer JP, et al. Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. N Engl J Med 2011; 365:1771.
- Buchholz U, Bernard H, Werber D, et al. German outbreak of Escherichia coli O104:H4 associated with sprouts. N Engl J Med 2011; 365:1763.
- Talan D, Moran GJ, Newdow M, et al. Etiology of bloody diarrhea among patients presenting to United States emergency departments: prevalence of Escherichia coli O157:H7 and other enteropathogens. Clin Infect Dis 2001; 32:573.
- Carter AO, Borczyk AA, Carlson JA, et al. A severe outbreak of Escherichia coli O157:H7--associated hemorrhagic colitis in a nursing home. N Engl J Med 1987; 317:1496.
- Johnson KE, Thorpe CM, Sears CL. The emerging clinical importance of non-O157 Shiga toxin-producing Escherichia coli. Clin Infect Dis 2006; 43:1587.
- Pai CH, Ahmed N, Lior H, et al. Epidemiology of sporadic diarrhea due to verocytotoxin-producing Escherichia coli: a two-year prospective study. J Infect Dis 1988; 157:1054.
- Jelacic JK, Damrow T, Chen GS, et al. Shiga toxin-producing Escherichia coli in Montana: bacterial genotypes and clinical profiles. J Infect Dis 2003; 188:719.
- Werber D, Fruth A, Heissenhuber A, et al. Shiga toxin-producing Escherichia coli O157 more frequently cause bloody diarrhea than do non-O157 strains. J Infect Dis 2004; 189:1335.
- Karmali MA, Petric M, Lim C, et al. The association between idiopathic hemolytic uremic syndrome and infection by verotoxin-producing Escherichia coli. J Infect Dis 1985; 151:775.
- Centers for Disease Control and Prevention (CDC). Preliminary FoodNet data on the incidence of infection with pathogens transmitted commonly through food - 10 states, 2009. MMWR Morb Mortal Wkly Rep 2010; 59:418.
- Siegler RL, Milligan MK, Burningham TH, et al. Long-term outcome and prognostic indicators in the hemolytic-uremic syndrome. J Pediatr 1991; 118:195.
- Fitzpatrick MM, Shah V, Trompeter RS, et al. Long term renal outcome of childhood haemolytic uraemic syndrome. BMJ 1991; 303:489.
- Mead PS, Griffin PM. Escherichia coli O157:H7. Lancet 1998; 352:1207.
- Rosales A, Hofer J, Zimmerhackl LB, et al. Need for long-term follow-up in enterohemorrhagic Escherichia coli-associated hemolytic uremic syndrome due to late-emerging sequelae. Clin Infect Dis 2012; 54:1413.
- Clark WF, Sontrop JM, Macnab JJ, et al. Long term risk for hypertension, renal impairment, and cardiovascular disease after gastroenteritis from drinking water contaminated with Escherichia coli O157:H7: a prospective cohort study. BMJ 2010; 341:c6020.
- Banatvala N, Griffin PM, Greene KD, et al. The United States National Prospective Hemolytic Uremic Syndrome Study: microbiologic, serologic, clinical, and epidemiologic findings. J Infect Dis 2001; 183:1063.
- Gerber A, Karch H, Allerberger F, et al. Clinical course and the role of shiga toxin-producing Escherichia coli infection in the hemolytic-uremic syndrome in pediatric patients, 1997-2000, in Germany and Austria: a prospective study. J Infect Dis 2002; 186:493.
- Stephan R, Untermann F. Virulence factors and phenotypical traits of verotoxin-producing Escherichia coli strains isolated from asymptomatic human carriers. J Clin Microbiol 1999; 37:1570.
- Spacek LA, Hurley BP, Acheson DW, et al. Shiga toxin-producing Escherichia coli as a possible etiological agent of chronic diarrhea. Clin Infect Dis 2004; 39:e46.
- Kendrick JB, Risbano M, Groshong SD, Frankel SK. A rare presentation of ischemic pseudomembranous colitis due to Escherichia coli O157:H7. Clin Infect Dis 2007; 45:217.
- Tarr PI, Neill MA, Clausen CR, et al. Escherichia coli O157:H7 and the hemolytic uremic syndrome: importance of early cultures in establishing the etiology. J Infect Dis 1990; 162:553.
- Mackenzie AM, Lebel P, Orrbine E, et al. Sensitivities and specificities of premier E. coli O157 and premier EHEC enzyme immunoassays for diagnosis of infection with verotxin (Shiga-like toxin)-producing Escherichia coli. The SYNSORB Pk Study investigators. J Clin Microbiol 1998; 36:1608.
- Kehl KS, Havens P, Behnke CE, Acheson DW. Evaluation of the premier EHEC assay for detection of Shiga toxin-producing Escherichia coli. J Clin Microbiol 1997; 35:2051.
- Centers for Disease Control and Prevention (CDC). Importance of culture confirmation of shiga toxin-producing Escherichia coli infection as illustrated by outbreaks of gastroenteritis--New York and North Carolina, 2005. MMWR Morb Mortal Wkly Rep 2006; 55:1042.
- Thielman NM, Guerrant RL. Clinical practice. Acute infectious diarrhea. N Engl J Med 2004; 350:38.
- Nelson JM, Griffin PM, Jones TF, et al. Antimicrobial and antimotility agent use in persons with shiga toxin-producing Escherichia coli O157 infection in FoodNet Sites. Clin Infect Dis 2011; 52:1130.
- Bell BP, Griffin PM, Lozano P, et al. Predictors of hemolytic uremic syndrome in children during a large outbreak of Escherichia coli O157:H7 infections. Pediatrics 1997; 100:E12.
- Proulx F, Turgeon JP, Delage G, et al. Randomized, controlled trial of antibiotic therapy for Escherichia coli O157:H7 enteritis. J Pediatr 1992; 121:299.
- Walterspiel JN, Ashkenazi S, Morrow AL, Cleary TG. Effect of subinhibitory concentrations of antibiotics on extracellular Shiga-like toxin I. Infection 1992; 20:25.
- Zhang X, McDaniel AD, Wolf LE, et al. Quinolone antibiotics induce Shiga toxin-encoding bacteriophages, toxin production, and death in mice. J Infect Dis 2000; 181:664.
- Pavia AT, Nichols CR, Green DP, et al. Hemolytic-uremic syndrome during an outbreak of Escherichia coli O157:H7 infections in institutions for mentally retarded persons: clinical and epidemiologic observations. J Pediatr 1990; 116:544.
- Wong CS, Jelacic S, Habeeb RL, et al. The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med 2000; 342:1930.
- Smith KE, Wilker PR, Reiter PL, et al. Antibiotic treatment of Escherichia coli O157 infection and the risk of hemolytic uremic syndrome, Minnesota. Pediatr Infect Dis J 2012; 31:37.
- Wong CS, Mooney JC, Brandt JR, et al. Risk factors for the hemolytic uremic syndrome in children infected with Escherichia coli O157:H7: a multivariable analysis. Clin Infect Dis 2012; 55:33.
- Menne J, Nitschke M, Stingele R, et al. Validation of treatment strategies for enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome: case-control study. BMJ 2012; 345:e4565.
- Vonberg RP, Höhle M, Aepfelbacher M, et al. Duration of fecal shedding of Shiga toxin-producing Escherichia coli O104:H4 in patients infected during the 2011 outbreak in Germany: a multicenter study. Clin Infect Dis 2013; 56:1132.
- Trachtman H, Cnaan A, Christen E, et al. Effect of an oral Shiga toxin-binding agent on diarrhea-associated hemolytic uremic syndrome in children: a randomized controlled trial. JAMA 2003; 290:1337.
- Watanabe M, Matsuoka K, Kita E, et al. Oral therapeutic agents with highly clustered globotriose for treatment of Shiga toxigenic Escherichia coli infections. J Infect Dis 2004; 189:360.