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Strains of E. coli are united by a core genome of ~2000 genes. A strain’s ability to cause infections and the nature of such infections are defined by ancillary genes that encode various virulence factors. This experiment of nature is fluid and ongoing, as demonstrated by the recent evolution of Shiga toxin–producing enteroaggregative E. coli.
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For the most part, commensal E. coli variants, which constitute the bulk of the normal facultative intestinal flora in most humans, confer benefits to the host (e.g., resistance to colonization with pathogenic organisms). These strains generally lack the specialized virulence traits that enable extraintestinal and intestinal pathogenic E. coli strains to cause disease outside and within the gastrointestinal tract, respectively. However, even commensal E. coli strains can be involved in extraintestinal infections in the presence of an aggravating factor, such as a foreign body (e.g., a urinary catheter), host compromise (e.g., local anatomic or functional abnormalities, such as urinary or biliary tract obstruction or systemic immunocompromise), or an inoculum that is large or contains a mixture of bacterial species (e.g., fecal contamination of the peritoneal cavity).
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EXTRAINTESTINAL PATHOGENIC STRAINS
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ExPEC strains are the most common enteric GNB to cause community-acquired and health care–associated bacterial infections. The emerging propensity of these strains to acquire new antimicrobial resistance mechanisms (e.g., ESBL and carbapenemase production) has posed challenges in managing ExPEC infection. One clonal group—ST131, the members of which are usually resistant to fluoroquinolones and increasingly express an ESBL (CTX-M)—has undergone global dissemination.
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Like commensal E. coli (but in contrast to intestinal pathogenic E. coli), ExPEC strains are often found in the intestinal flora of healthy individuals and do not cause gastroenteritis in humans. Entry from their site of colonization (e.g., the colon, vagina, or oropharynx) into a normally sterile extraintestinal site (e.g., the urinary tract, peritoneal cavity, or lungs) is the rate-limiting step for infection. ExPEC strains have acquired genes encoding diverse extraintestinal virulence factors that enable the bacteria to cause infections outside the gastrointestinal tract in both normal and compromised hosts (Table 186-1). These virulence genes define ExPEC and, for the most part, are distinct from those that enable intestinal pathogenic strains to cause diarrheal disease (Table 186-2). All age groups, all types of hosts, and nearly all organs and anatomic sites are susceptible to infection by ExPEC. Even previously healthy hosts can become severely ill or die when infected with ExPEC; however, adverse outcomes are more common among hosts with comorbid illnesses and host defense abnormalities. The diversity and the medical and economic impact of ExPEC infections are evident from consideration of the following specific syndromes.
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Extraintestinal Infectious Syndromes
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URINARY TRACT INFECTION
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The urinary tract is the site most frequently infected by ExPEC. An exceedingly common infection among ambulatory patients, UTI accounts for 1% of ambulatory care visits in the United States and is second only to lower respiratory tract infection among infections responsible for hospitalization. UTIs are best considered by clinical syndrome (e.g., uncomplicated cystitis, pyelonephritis, and catheter-associated UTIs) and within the context of specific hosts (e.g., premenopausal women, compromised hosts; Chap. 162). E. coli is the single most common pathogen for all UTI syndrome/host group combinations. Each year in the United States, E. coli causes 80–90% of an estimated 6–8 million episodes of uncomplicated cystitis in premenopausal women. Furthermore, 20% of women with an initial cystitis episode develop frequent recurrences.
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Uncomplicated cystitis, the most common acute UTI syndrome, is characterized by dysuria, urinary frequency, and suprapubic pain. Fever and/or back pain suggests progression to pyelonephritis. Even with appropriate treatment of pyelonephritis, fever may take 5–7 days to resolve completely. Persistently elevated or increasing fever and neutrophil counts should prompt evaluation for intrarenal or perinephric abscess and/or obstruction. Renal parenchymal damage and loss of renal function during pyelonephritis occur primarily with urinary obstruction, which can be preexisting or, rarely, occurs de novo in diabetic patients who develop renal papillary necrosis as a result of kidney infection. Pregnant women are at unusually high risk for developing pyelonephritis, which can adversely affect the outcome of pregnancy. As a result, prenatal screening for and treatment of asymptomatic bacteriuria are standard. Prostatic infection is a potential complication of UTI in men. The diagnosis and treatment of UTI, as detailed in Chap. 162, should be tailored to the individual host, the nature and site of infection, and local patterns of antimicrobial susceptibility.
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ABDOMINAL AND PELVIC INFECTION
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The abdomen/pelvis is the second most common site of extraintestinal infection due to E. coli. A wide variety of clinical syndromes occur in this location, including acute peritonitis secondary to fecal contamination, spontaneous bacterial peritonitis, dialysis-associated peritonitis, diverticulitis, appendicitis, intraperitoneal or visceral abscesses (hepatic, pancreatic, splenic), infected pancreatic pseudocysts, and septic cholangitis and/or cholecystitis. In intraabdominal infections, E. coli can be isolated either alone or (as often occurs) in combination with other facultative and/or anaerobic members of the intestinal flora (Chap. 159).
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E. coli is not usually considered a cause of pneumonia (Chap. 153). Indeed, enteric GNB account for only 1–3% of cases of community-acquired pneumonia, in part because these organisms only transiently colonize the oropharynx in a minority of healthy individuals. However, rates of oral colonization with E. coli and other GNB increase with severity of illness and antibiotic use. Consequently, GNB are a more common cause of pneumonia among residents of LTCFs and are the most common cause (60–70% of cases) of hospital-acquired pneumonia (Chap. 168), particularly among postoperative and ICU patients (e.g., ventilator-associated pneumonia). Pulmonary infection is usually acquired by small-volume aspiration but occasionally occurs via hematogenous spread, in which case multifocal nodular infiltrates can be seen. Tissue necrosis, probably due to bacterial cytotoxins, is common. Despite significant institutional variation, E. coli is generally the third or fourth most commonly isolated GNB in hospital-acquired pneumonia, accounting for 5–8% of episodes in both U.S.-based and Europe-based studies. Regardless of the host, pneumonia due to ExPEC is a serious disease, with high crude and attributable mortality rates (20–60% and 10–20%, respectively).
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(See also Chap. 164) E. coli is one of the two leading causes of neonatal meningitis, the other being group B Streptococcus. Most E. coli strains that cause neonatal meningitis possess the K1 capsular antigen and derive from a limited number of meningitis-associated clonal groups. Ventriculomegaly commonly occurs. After the first month of life, E. coli meningitis is uncommon, occurring predominantly in the setting of surgical or traumatic disruption of the meninges or in the presence of cirrhosis. In patients with cirrhosis who develop meningitis, the meninges are presumably seeded as a result of poor hepatic clearance of portal vein bacteremia.
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CELLULITIS/MUSCULOSKELETAL INFECTION
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E. coli contributes frequently to infections of decubitus ulcers and occasionally to infections of ulcers and wounds of the lower extremity in diabetic patients and other hosts with neurovascular compromise. Osteomyelitis secondary to contiguous spread can occur in these settings. E. coli also causes cellulitis or infections of burn sites and surgical wounds (accounting for ~10% of surgical site infections), particularly when the infection originates close to the perineum. Hematogenously acquired osteomyelitis, especially of vertebral bodies, is more commonly caused by E. coli than is generally appreciated; this organism accounts for up to 10% of cases in some series (Chap. 158). E. coli occasionally causes orthopedic device–associated infection or septic arthritis and rarely causes hematogenous myositis. Upper-leg myositis or fasciitis due to E. coli should prompt an evaluation for an abdominal source with contiguous spread.
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ENDOVASCULAR INFECTION
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Despite being one of the most common causes of bacteremia, E. coli rarely seeds native heart valves. When the organism does seed native valves, it usually does so in the setting of prior valvular disease. E. coli infections of aneurysms, the portal vein (pylephlebitis), and vascular grafts are quite uncommon.
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MISCELLANEOUS INFECTIONS
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E. coli can cause infection in nearly every organ and anatomic site. It occasionally causes postoperative mediastinitis or complicated sinusitis and uncommonly causes endophthalmitis, ecthyma gangrenosum, or brain abscess.
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E. coli bacteremia can arise from primary infection at any extraintestinal site. In addition, primary E. coli bacteremia can arise from percutaneous intravascular devices or transrectal prostate biopsy or from the increased intestinal mucosal permeability seen in neonates and in the settings of neutropenia and chemotherapy-induced mucositis, trauma, and burns. Roughly equal proportions of E. coli bacteremia cases originate in the community and in health care settings. In most studies, E. coli and Staphylococcus aureus are the two most common blood isolates of clinical significance. Isolation of E. coli from the blood is almost always clinically significant and is typically accompanied by the sepsis syndrome, severe sepsis (sepsis-induced dysfunction of at least one organ or system), or septic shock (Chap. 325).
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The urinary tract is the most common source of E. coli bacteremia, accounting for one-half to two-thirds of episodes. Bacteremia from a urinary tract source is particularly common among patients with pyelonephritis, urinary tract obstruction, or urinary instrumentation in the presence of infected urine. The abdomen is the second most common source, accounting for 25% of episodes. Although biliary obstruction (stones, tumor) and overt bowel disruption, which typically are readily apparent, are responsible for many of these cases, some abdominal sources (e.g., abscesses) are remarkably silent clinically and require identification via imaging studies (e.g., CT). Therefore, the physician should be cautious in designating the urinary tract as the source of E. coli bacteremia in the absence of characteristic signs and symptoms of UTI. Soft tissue, bone, pulmonary, and intravascular catheter infections are other sources of E. coli bacteremia.
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Strains of E. coli that cause extraintestinal infections usually grow both aerobically and anaerobically within 24 h on standard diagnostic media and are easily identified by the clinical microbiology laboratory according to routine biochemical criteria. More than 90% of ExPEC strains are rapid lactose fermenters and are indole positive.
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TREATMENT Extraintestinal E. Coli Infections
In the past, most E. coli isolates were highly susceptible to a broad range of antimicrobial agents. Unfortunately, this situation has changed. In general, the high prevalence of resistance precludes empirical use of ampicillin and amoxicillin-clavulanate, even for community-acquired infections. The prevalence of resistance to first-generation cephalosporins and TMP-SMX is increasing among community-acquired strains in the United States (with current rates of 10–40%) and is even higher outside North America. Until recently, TMP-SMX was the drug of choice for the treatment of uncomplicated cystitis in many locales. Although continued empirical use of TMP-SMX will predictably result in ever-diminishing cure rates, a wholesale switch to alternative agents (e.g., fluoroquinolones) will just as predictably accelerate the widespread emergence of resistance to these antimicrobial classes, as has already occurred in some areas. More than 90% of isolates that cause uncomplicated cystitis remain susceptible to nitrofurantoin and fosfomycin.
The prevalence of resistance to fluoroquinolones among E. coli isolates from U.S. outpatients has increased steadily over the last decade (i.e., from 3% in 2000 to 17.1% in 2010, according to one survey). Resistance rates are generally higher in the ambulatory setting outside the United States and are even higher in populations for which fluoroquinolone prophylaxis is used extensively (e.g., patients with leukemia, transplant recipients, and patients with cirrhosis) and among isolates from LTCFs and hospitals. For example, the National Healthcare Safety Network (NHSN) reported fluoroquinolone resistance in 41.8% of central line–associated bloodstream infection (CLABSI) E. coli isolates in 2009–2010, and the International Nosocomial Infection Control Consortium (INICC) reported that 53.4% of ICU E. coli isolates were resistant to quinolones in 2004–2009. Furthermore, the NHSN reported 19% resistance to third- and fourth-generation cephalosporins in CLABSI E. coli isolates, and the INICC found that 66.6% of ICU E. coli isolates were resistant to third-generation cephalosporins.
ESBL-producing strains are increasingly prevalent among both health care–associated (5–10%) and ambulatory isolates (region-dependent figures). An increasing number of reports describe community-acquired UTIs caused by E. coli strains that produce CTX-M ESBLs. Data suggest that acquisition of CTX-M-producing, fluoroquinolone-resistant strains may result from consumption of meat products from food animals treated with third- and fourth-generation cephalosporins and fluoroquinolones. Oral treatment options for such strains are limited; however, in vitro and limited clinical data indicate that, for cystitis, fosfomycin and nitrofurantoin appear to be useful options. Carbapenems and amikacin are the most predictably active agents overall, but carbapenemase-producing strains are on the rise (1–5% among health care–associated isolates in the United States and higher rates in many other countries). Tigecycline and the polymyxins, with or without a second agent, have been used most frequently against these extremely resistant isolates.
This evolving antimicrobial resistance—a source of serious concern—necessitates not only the increasing use of broad-spectrum agents but also the use of the most appropriate narrower-spectrum agent whenever possible and the avoidance of treatment of colonized but uninfected patients.
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INTESTINAL PATHOGENIC STRAINS
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Certain strains of E. coli are capable of causing diarrheal disease. Other important intestinal pathogens are discussed in Chaps. 160, 161, and 190, 191, 192, and 193. At least in the industrialized world, intestinal pathogenic strains of E. coli are rarely encountered in the fecal flora of healthy persons and instead appear to be essentially obligate pathogens. These strains have evolved a special ability to cause enteritis, enterocolitis, and colitis when ingested in sufficient quantities by a naive host. At least five distinct pathotypes of intestinal pathogenic E. coli exist: (1) Shiga toxin–producing E. coli (STEC), which includes the subsets of enterohemorrhagic E. coli (EHEC) and the recently evolved Shiga toxin–producing enteroaggregative E. coli (STEAEC); (2) enterotoxigenic E. coli (ETEC); (3) enteropathogenic E. coli (EPEC); (4) enteroinvasive E. coli (EIEC); and (5) enteroaggregative E. coli (EAEC). Diffusely adherent E. coli (DAEC) and cytodetaching E. coli are additional putative pathotypes. Lastly, a variant termed adherent invasive E. coli (AIEC) has been associated with Crohn’s disease (although a causal role remains unproven) but does not cause acute diarrheal disease. Transmission occurs predominantly via contaminated food and water for ETEC, STEC/EHEC/STEAEC, EIEC, and EAEC and by person-to-person spread for EPEC (and occasionally STEC/EHEC/STEAEC). Gastric acidity confers some protection against infection; therefore, persons with decreased stomach acid levels are especially susceptible. Humans are the major reservoir (except for STEC/EHEC, with regard to which bovines are the main concern); host range appears to be dictated by species-specific attachment factors. Although there is some overlap, each patho-type possesses a largely unique combination of virulence traits that results in a distinctive intestinal pathogenic mechanism (Table 186-2). These strains are largely incapable of causing disease outside the intestinal tract. Except in the cases of STEC/EHEC/STEAEC and EAEC, disease due to this group of pathogens occurs primarily in developing countries.
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ENTEROHEMORRHAGIC E. COLI/SHIGA TOXIN–PRODUCING ENTEROAGGREGATIVE E. COLI
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STEC/EHEC/STEAEC strains constitute an emerging group of pathogens that can cause hemorrhagic colitis and the hemolytic-uremic syndrome (HUS). Several large outbreaks resulting from the consumption of fresh produce (e.g., lettuce, spinach, sprouts) and of undercooked ground beef have received significant attention in the media. An outbreak in central Europe in 2011 due to STEAEC (O104:H4) that was probably transmitted by sprouts, with some subsequent human-to-human transmission, resulted in more than 800 cases of HUS and 54 deaths. Within this group of organisms, O157:H7 is the most prominent serotype, but many other serotypes have also been associated with these syndromes, including O6, O26, O45, O55, O91, O103, O111, O113, O121, O145, and OX3.
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The ability of STEC/EHEC/STEAEC to produce Shiga toxin (Stx2 and/or Stx1) or related toxins is a critical factor in the occurrence of clinical disease. Shigella dysenteriae strains that produce the closely related Shiga toxin Stx can cause the same syndrome. Stx2 and its Stx2C variant (which may be variably present in combination with Stx2 and/or Stx1) appear to be more important than Stx1 in the development of HUS. All Shiga toxins studied to date are multimers comprising one enzymatically active A subunit and five identical B subunits that mediate binding to globosyl ceramides, which are membrane-associated glycolipids expressed on certain host cells. As in ricin, the A subunit cleaves an adenine from the host cell’s 28S rRNA, thereby irreversibly inhibiting ribosomal function and potentially leading to apoptosis. Stx2-mediated activation of complement may also play a role in the development of HUS.
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Additional properties, such as acid tolerance and epithelial cell adherence, are necessary for full pathogenicity among STEC strains. Most disease-causing isolates possess the chromosomal locus for enterocyte effacement (LEE). This pathogenicity island was first described in EPEC strains and contains genes that mediate adherence to intestinal epithelial cells and a system that subverts host cells by the translocation of bacterial proteins (type III secretion system). EHEC strains make up the subgroup of STEC strains that possess stx1 and/or stx2 as well as LEE. STEAEC (LEE-negative) evolved from EAEC via the acquisition of a number of genes, including those that encode Stx2, the Iha adhesin, tellurite resistance, a type VI secretion system, and the CTX-M-15 ESBL.
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Domesticated ruminant animals, particularly cattle and young calves, serve as the major reservoir for STEC/EHEC. Ground beef—the most common food source of STEC/EHEC strains—is often contaminated during processing. Furthermore, manure from cattle or other animals (including that in the form of fertilizer) can contaminate produce (potatoes, lettuce, spinach, sprouts, fallen fruits, nuts, strawberries), and fecal runoff from this source can contaminate water systems. Dairy products and petting zoos are additional sources of infection. By contrast, humans appear to be the reservoir for STEAEC. It is estimated that <102 colony-forming units (CFU) of STEC/EHEC/STEAEC can cause disease. Therefore, not only can low levels of food or environmental contamination (e.g., in water swallowed while swimming) result in disease, but person-to-person transmission (e.g., at day-care centers and in institutions) is an important route for secondary spread. Laboratory-associated infections also occur. Illness due to this group of pathogens occurs both as outbreaks and as sporadic cases, with a peak incidence in the summer months.
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In contrast to other intestinal pathotypes, STEC/EHEC/STEAEC causes infections more frequently in industrialized countries than in developing regions. O157:H7 strains are the fourth most commonly reported cause of bacterial diarrhea in the United States (after Campylobacter, Salmonella, and Shigella). Colonization of the colon and perhaps the ileum results in symptoms after an incubation period of 3 or 4 days. Colonic edema and an initial nonbloody secretory diarrhea may develop into the STEC/EHEC/STEAEC hallmark syndrome of grossly bloody diarrhea (identified by history or examination) in >90% of cases. Significant abdominal pain and fecal leukocytes are common (70% of cases), whereas fever is not; absence of fever can incorrectly lead to consideration of noninfectious conditions (e.g., intussusception and inflammatory or ischemic bowel disease). Occasionally, infections caused by C. difficile, K. oxytoca (see “Klebsiella Infections,” below), Campylobacter, and Salmonella present in a similar fashion. STEC/EHEC disease is usually self-limited, lasting 5–10 days. An uncommon but feared complication of this infection is HUS, which occurs 2–14 days after diarrhea in 2–8% of cases, most often affecting very young or elderly patients. Distinctive features of STEAEC infection, as compared with classical STEC/EHEC disease, include a higher incidence among adults, especially young women, and a higher rate of HUS (~20%). It is estimated that >50% of all cases of HUS in the United States and 90% of HUS cases in children are caused by STEC/EHEC. This complication is mediated by the systemic translocation of Shiga toxins. Erythrocytes may serve as carriers of Stx to endothelial cells located in the small vessels of the kidney and brain. The subsequent development of thrombotic microangiopathy (perhaps with direct toxin-mediated effects on various nonendothelial cells) commonly produces some combination of fever, thrombocytopenia, renal failure, and encephalopathy. Although the mortality rate with dialysis support is <10%, residual renal and neurologic dysfunction may persist.
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ENTEROTOXIGENIC E. COLI
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In tropical or developing countries, ETEC is a major cause of endemic diarrhea. After weaning, children in these locales commonly experience several episodes of ETEC infection during the first 3 years of life. The incidence of disease diminishes with age, a pattern that correlates with the development of mucosal immunity to colonization factors (i.e., adhesins). In industrialized countries, infection usually follows travel to endemic areas, although occasional food-borne outbreaks occur. ETEC is the most common agent of traveler’s diarrhea, causing 25–75% of cases. The incidence of infection may be decreased by prudent avoidance of potentially contaminated fluids and foods, particularly items that are poorly cooked, unpeeled, or unrefrigerated (Chap. 149). ETEC infection is uncommon in the United States, but outbreaks secondary to consumption of food products imported from endemic areas have occurred. A large inoculum (106–1010 CFU) is needed to produce disease, which usually develops after an incubation period of 12–72 h.
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After adherence of ETEC via colonization factors (e.g., CFA/I, CS1-6), disease is mediated primarily by a heat-labile toxin (LT-1) and/or a heat-stable toxin (STa) that causes net fluid secretion via activation of adenylate cyclase (LT-1) and/or guanylate cyclase (STa) in the jejunum and ileum. The result is watery diarrhea accompanied by cramps. LT-1 consists of an A and a B subunit and is structurally and functionally similar to cholera toxin. Strong binding of the B subunit to the GM1 ganglioside on intestinal epithelial cells leads to the intracellular translocation of the A subunit, which functions as an ADP-ribosyltransferase. Mature STa is an 18- or 19-amino-acid secreted peptide whose biologic activity is mediated by binding to the guanylate cyclase C found in the brush-border membrane of enterocytes and results in increased intracellular concentrations of cyclic GMP. Characteristically absent in ETEC-mediated disease are histopathologic changes within the small bowel; mucus, blood, and inflammatory cells in stool; and fever. The disease spectrum ranges from a mild illness to a life-threatening cholera-like syndrome. Although symptoms are usually self-limited (typically lasting for 3 days), infection may result in significant morbidity and mortality (mostly from profound volume depletion) when access to health care or suitable rehydration fluids is limited and when small and/or undernourished children are affected.
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ENTEROPATHOGENIC E. COLI
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EPEC causes disease primarily in young children, including neonates. The first E. coli pathotype recognized as an agent of diarrheal disease, EPEC was responsible for outbreaks of infantile diarrhea (including some outbreaks in hospital nurseries) in industrialized countries in the 1940s and 1950s. At present, EPEC infection is an uncommon cause of diarrhea in developed countries but is an important cause of diarrhea (both sporadic and epidemic) among infants in developing countries. Breast-feeding diminishes the incidence of EPEC infection. Rapid person-to-person spread may occur. Upon colonization of the small bowel, symptoms develop after a brief incubation period (1 or 2 days). Initial localized adherence via bundle-forming pili leads to a characteristic effacement of microvilli, with the formation of cuplike, actin-rich pedestals mediated by factors in the LEE. Diarrhea production is a complex and regulated process in which host cell modulation by a type III secretion system plays an important role. Strains lacking bundle-forming pili have been categorized as atypical EPEC (aEPEC); increasing data support a role for these strains as intestinal pathogens. Diarrheal stool often contains mucus but not blood. Although EPEC diarrhea is usually self-limited (lasting 5–15 days), it may persist for weeks.
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ENTEROINVASIVE E. COLI
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EIEC, a relatively uncommon cause of diarrhea, is rarely identified in the United States, although a few food-related outbreaks have been described. In developing countries, sporadic disease is infrequently recognized in children and travelers. EIEC shares many genetic and clinical features with Shigella, both of which evolved from a common ancestor. However, unlike Shigella, EIEC produces disease only with a large inoculum (108–1010 CFU), with onset generally following an incubation period of 1–3 days. Initially, enterotoxins are believed to induce secretory small-bowel diarrhea. Subsequently, colonization and invasion of the colonic mucosa, followed by replication therein and cell-to-cell spread, result in the development of inflammatory colitis characterized by fever, abdominal pain, tenesmus, and scant stool containing mucus, blood, and inflammatory cells. Symptoms are usually self-limited (7–10 days).
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ENTEROAGGREGATIVE AND DIFFUSELY ADHERENT E. COLI
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EAEC has been described primarily in developing countries and in young children. However, recent studies indicate that it may be a relatively common cause of diarrhea in all age groups in industrialized countries. EAEC has also been recognized increasingly as an important cause of traveler’s diarrhea. It is highly adapted to humans, the probable reservoir. A large inoculum is required for infection, which usually manifests as watery and sometimes persistent diarrhea in healthy, malnourished, and HIV-infected hosts. In vitro, the organisms exhibit a diffuse or “stacked-brick” pattern of adherence to small-intestine epithelial cells. Virulence factors that probably are necessary for disease are regulated in part by the transcriptional activator AggR and include the aggregative adherence fimbriae (AAF/I-III); the Hda adhesin; the mucinase Pic; the enterotoxins Pet, EAST-1, ShET1, and HlyE; and dispersin, an antiaggregation protein that promotes mucosal spread. Some strains of DAEC are capable of causing diarrheal disease, primarily in children 2–6 years of age in some developing countries, and may perhaps cause traveler’s diarrhea. The Afa/Dr adhesins may contribute to the pathogenesis of such infections.
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A practical approach to the evaluation of diarrhea is to distinguish noninflammatory from inflammatory cases; the latter is suggested by grossly bloody or mucoid stool or a positive test for fecal leukocytes (Chap. 160). ETEC, EPEC, and DAEC cause noninflammatory diarrhea and are uncommon in the United States; in this country, the incidence of EAEC infection, which also causes noninflammatory diarrhea, may be underrecognized. The diagnosis of these infections requires specialized assays (e.g., polymerase chain reaction–based tests for pathotype-specific genes) that are not routinely available and are rarely needed because the diseases are self-limited. ETEC causes the majority and EAEC a minority of cases of noninflammatory traveler’s diarrhea. Definitive diagnosis generally is not necessary. Empirical antimicrobial (or symptom-based) treatment, along with rehydration therapy, is a reasonable approach. If diarrhea persists for >10 days despite treatment, Giardia or Cryptosporidium (or, in immunocompromised hosts, certain other microbial agents) should be sought. The diagnosis of infection with EIEC, a rare cause of inflammatory diarrhea in the United States, also requires specialized assays. The CDC now recommends that all patients with community-acquired diarrhea, whether inflammatory or not, be evaluated for STEC/EHEC/STEAEC infection by simultaneous culture (which is important for outbreak detection and control) and assay for the detection of Shiga toxin or its associated genes. The reasons for this recommendation are that bloody stool is not always present and detection of fecal white blood cells is not optimally sensitive for the diagnosis of STEC/EHEC/STEAEC infection. The use of both tests increases the rate of identification of infection over rates obtained with either test alone. O157 STEC/EHEC may be identified via culture by screening for E. coli strains that do not ferment sorbitol, with subsequent serotyping and testing for Shiga toxin. Selective or screening media are not available for the culture of non-O157 strains. Detection of Shiga toxins or toxin genes via DNA-based, enzyme-linked immunosorbent, and cytotoxicity assays offers the advantages of rapidity plus detection of non-O157 STEC/EHEC/STEAEC strains. Specimens positive for toxin but culture-negative for O157 should be forwarded to the local or state public health laboratory.
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TREATMENT Intestinal E. Coli Infections
(See also Chap. 128) The mainstay of treatment for all diarrheal syndromes is replacement of water and electrolytes. This measure is especially important for STEC/EHEC/STEAEC infection because appropriate volume expansion may decrease renal damage and improve outcome. The use of prophylactic antibiotics to prevent traveler’s diarrhea generally should be discouraged, especially in light of high rates of antimicrobial resistance. However, in selected patients (e.g., those who cannot afford a brief illness or are predisposed to infection), the use of rifaximin, which is nonabsorbable and is well tolerated, is reasonable. When stools are free of mucus and blood, early patient-initiated treatment of traveler’s diarrhea with a fluoroquinolone or azithromycin decreases the duration of illness, and the use of loperamide may halt symptoms within a few hours. Although dysentery caused by EIEC is self-limited, treatment hastens the resolution of symptoms, particularly in severe cases. In contrast, antimicrobial therapy for STEC/EHEC/STEAEC infection (the presence of which is suggested by grossly bloody diarrhea without fever) should be avoided because antibiotics may increase the incidence of HUS (possibly via increased production/release of Stx). The role of plasmapheresis and inhibition of C5 (eculizumab) in the treatment of HUS is unresolved.