Escherichia ColiEscherichia Coli

Infectious Diseases, AIDS & Clinical Immunology Research Center –Tbilisi

Escherichia coli species are components Escherichia coli species are components of the of the – Normal animal and human colonic Normal animal and human colonic

flora; flora; – Flora of a variety of environmental Flora of a variety of environmental

habitats, including long-term care habitats, including long-term care facilities (LTCFs) and hospitals. facilities (LTCFs) and hospitals.

E.coli are the cause of most nosocomial E.coli are the cause of most nosocomial infections.infections.

Commensal strainsCommensal strains Extraintestinal pathogenic Extraintestinal pathogenic

(ExPEC) strains(ExPEC) strains Intestinal pathogenic strainsIntestinal pathogenic strains

Commensal strainsCommensal strains

In most humans, commensal strains of E. coli In most humans, commensal strains of E. coli constitute the bulk of the normal facultative constitute the bulk of the normal facultative intestinal flora and confer benefits to the host intestinal flora and confer benefits to the host (e.g. resistance to colonization with pathogenic (e.g. resistance to colonization with pathogenic organisms).organisms).

Commensal strains generally lack the Commensal strains generally lack the specialized virulence traits.specialized virulence traits.

These strains do not cause disease outside and These strains do not cause disease outside and within the gastrointestinal tract.within the gastrointestinal tract.

Rarely commensal E. coli strains can be Rarely commensal E. coli strains can be involved in extraintestinal infections in the involved in extraintestinal infections in the presence of an aggravating factor:presence of an aggravating factor:•Foreign body (e.g. urinary catheter)Foreign body (e.g. urinary catheter)•Host compromise (e.g. local anatomic or Host compromise (e.g. local anatomic or functional abnormalities such as urinary or functional abnormalities such as urinary or biliary tract obstruction or systemic biliary tract obstruction or systemic immunocompromised)immunocompromised)•Inoculums that is large or contains a mixture of Inoculums that is large or contains a mixture of bacterial species (e.g. fecal contamination of bacterial species (e.g. fecal contamination of the peritoneal cavity).the peritoneal cavity).

Extraintestinal pathogenic Extraintestinal pathogenic (EXPEC) strains(EXPEC) strains Like commensal E. coli (but in contrast to Like commensal E. coli (but in contrast to

intestinal pathogenic E.coli) ExPEC strains intestinal pathogenic E.coli) ExPEC strains are often found in the normal intestinal flora are often found in the normal intestinal flora and do not cause gastroenteritis in humans. and do not cause gastroenteritis in humans.

E.coli is the most common enteric gram-E.coli is the most common enteric gram-negative species to cause extraintestinal negative species to cause extraintestinal infection in ambulatory and hospital settings.infection in ambulatory and hospital settings.

Extraintestinal pathogenic Extraintestinal pathogenic (EXPEC) strains(EXPEC) strains

The majority of ExPEC strains isolates The majority of ExPEC strains isolates from symptomatic infections of thefrom symptomatic infections of theUrinary tract, Urinary tract, Bloodstream, Bloodstream, Cerebrospinal fluid, Cerebrospinal fluid, Respiratory tract,Respiratory tract,Peritoneum (spontaneous bacterial Peritoneum (spontaneous bacterial peritonitis).peritonitis).

ExPEC strains can also cause:ExPEC strains can also cause:Surgical wound infectionSurgical wound infectionOsteomielitisOsteomielitismyositismyositis

Extraintestinal Infectious Extraintestinal Infectious SyndromesSyndromes

Urinary tract infection (UTI)Urinary tract infection (UTI) Abdominal and pelvic infectionAbdominal and pelvic infection PneumoniaPneumonia MeningitisMeningitis Cellulitis/musculoskeletal infectionCellulitis/musculoskeletal infection Endovascular infectionEndovascular infection Miscellaneous infectionMiscellaneous infection bacteremiabacteremia

Urinary tract infection (UTI)Urinary tract infection (UTI)

The urinary tract is the most frequently The urinary tract is the most frequently infected by ExPEC.infected by ExPEC.

UTI accounts for 1% of ambulatory care visits UTI accounts for 1% of ambulatory care visits in USA.in USA.

UTI is second reason of hospitalization after UTI is second reason of hospitalization after lower respiratory tract infections.lower respiratory tract infections.

Urinary tract infection (UTI)Urinary tract infection (UTI)

Clinical syndromeClinical syndromeUncomplicated cystitis (dysuria, suprapubic Uncomplicated cystitis (dysuria, suprapubic pain)pain)Pyelonephritis (fever, back pain)Pyelonephritis (fever, back pain)

Specific hostSpecific hostPremenopausal womenPremenopausal womenCompromised hostsCompromised hosts

Treatment of ExPEC Treatment of ExPEC

E. coli is the species in which resistance is E. coli is the species in which resistance is evolving most rapidly.evolving most rapidly.

Until recently, TMP-SMX was the drug of choice Until recently, TMP-SMX was the drug of choice for the treatment of uncomplicated cystitis in for the treatment of uncomplicated cystitis in many locales.many locales.

The prevalence of resistance to cephalosporins I The prevalence of resistance to cephalosporins I and trimethoprim-sulfamethoxazole (TMP-SMX) is and trimethoprim-sulfamethoxazole (TMP-SMX) is increasingincreasing

among community-acquired strains in the United among community-acquired strains in the United States.States.

More than 90% of isolates that cause More than 90% of isolates that cause uncomplicated cystitis remain susceptible to uncomplicated cystitis remain susceptible to nitrofurantoin and fosfomycin. nitrofurantoin and fosfomycin.

The prevalence of resistance to fluoroquinolones The prevalence of resistance to fluoroquinolones has increased steadily over the last decade.has increased steadily over the last decade.

ESBL-containing strains are increasingly prevalent ESBL-containing strains are increasingly prevalent among both health care–associated (5–10%) and among both health care–associated (5–10%) and ambulatory isolates.ambulatory isolates.

fosfomycin and nitrofurantoin appear to be fosfomycin and nitrofurantoin appear to be viable options for cystitis.viable options for cystitis.

Carbapenems (e.g., imipenem) and amikacin Carbapenems (e.g., imipenem) and amikacin are the most predictably active agents are the most predictably active agents overall.overall.

Intestinal Pathogenic Strains

Certain strains of E. coli are capable of causing diarrheal disease..

Enterohemorrhagic E. coli (Shiga Toxin–Producing) (STEC/EHEC)Enterotoxigenic E. coli (ETEC)Enteropathogenic E. coli (EPEC)Enteroinvasive E. coli (EIEC)Enteroaggregative and Diffusely Adherent E. coli (EAEC)

Intestinal Pathogenic Strains

IIntestinal pathogenic strains of E. coli are rarely encountered in the fecal flora of healthy persons and instead appear to be essentially obligate pathogens.

CCause enteritis, enterocolitis, and colitis. Transmission occurs predominantly via

contaminated food and water for ETEC, STEC, EIEC, and probably EAEC and by person-to-person spread for EPEC (and occasionally STEC/EHEC).

Intestinal Pathogenic Strains

Gastric acidity confers some protection against infection.

Humans are the major reservoir (except for STEC/EHEC).

These strains are largely incapable of causing disease outside the intestinal tract..

Except in the case of STEC/EHEC and perhaps EAEC, disease due to this group of pathogens occurs primarily in developing countries.

Enterohemorrhagic E. coli (Shiga Toxin–Producing) (STEC/EHEC)

STEC/EHEC 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 undercooked ground beef and other foods (e.g., fresh spinach).

O157:H7 is the most prominent serotype.

Enterohemorrhagic E. coli (Shiga Toxin–Producing) (STEC/EHEC) In contrast to other intestinal pathotypes,

STEC/EHEC 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).

Illness due to this group of pathogens occurs both as outbreaks and as sporadic cases, with a peak incidence in the summer months.

TransmissionTransmission

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.

manure from cattle or other animals that is used as fertilizer can contaminate product (potatoes, lettuce, spinach, sprouts, fallen apples), and fecal runoff from this source can contaminate water.

It is estimated that <103 CFU of STEC/EHEC can cause disease.

person-to-person transmission (e.g., at day-care centers and in institutions) is an important route for secondary spread.

Clinical ManifestationClinical Manifestation

IIncubation period is 3 or 4 days.

Colonic edema and an initial secretory diarrhea may develop into the STEC/EHEC hallmark syndrome of grossly bloody diarrhea in >90% of cases.

Significant abdominal pain and fecal leukocytes in 70% of cases.

Fever is not common.

STEC/EHEC disease is usually self-limited, lasting 5–10 days.

This infection can be complicated by HUS, which occurs 2–14 days after diarrhea in 2–8% of cases and most often affects very young or elderly patients.

It is estimated that >50% of all cases of HUS in the United States are caused by STEC/EHEC.

HUSHUS

This complication is probably mediated by the systemic translocation of Shiga toxins.

Erythrocytes may serve as carriers of Stx to Erythrocytes may serve as carriers of Stx to endothelial cells located in the small vessels of endothelial cells located in the small vessels of the kidney and brain.the kidney and brain.

Thrombotic microangiopathy (perhaps with direct toxin-mediated effects on various nonendothelial cells) commonly produces some combination of fever, thrombocytopenia, renal failure, and encephalopathy.

Mortality rate with dialysis support is <10%, residual renal and neurologic dysfunction may persist.

Enterotoxigenic E. coli (ETEC)

In tropical or developing countries, ETEC is a major cause of endemic diarrhea.

In industrialized countries, infection usually follows travel to endemic areas.

ETEC is the most common agent of traveler's diarrhea, causing 25–75% of cases.

Transmission occurs predominantly via contaminated food and water.

Incubation period – 12-72 h.Incubation period – 12-72 h.

The disease spectrum ranges from a mild illness to a life-threatening cholera-like syndrome.

Symptoms are usually self-limited (typically lasting for 3 days).

Infection may result in significant morbidity and mortality when access to health care is limited and when small and/or undernourished children are affected.

Characteristically absent are histopathologic changes within the small bowel; mucus, blood, and inflammatory cells in stool; and fever

Enteropathogenic E. coli (EPEC)

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.

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.

Incubation period - 1 or 2 days.

Diarrheal stool often contains mucus but not blood.

Usually self-limited (lasting 5–15 days).

EPEC diarrhea may persist for weeks.

Enteroinvasive E. coli (EIEC)

EIEC, a relatively uncommon cause of diarrhea.

EIEC shares many genetic and clinical features with Shigella..

Incubation period - 1–3 days.

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).

Enteroaggregative and Diffusely Adherent E. coli (EAEC)

EAEC has been described primarily in developing countries and in young children.

EAEC is a relatively common cause of diarrhea in all age groups in industrialized countries.

Watery, sometimes prolonged diarrhea.

Some but not all strains of DAEC are capable of causing diarrheal disease, primarily in children 2–6 years of age in some developing countries.

TreatmentTreatment

The mainstay of treatment for all diarrheal syndromes is replacement of water and electrolytes.

The use of prophylactic antibiotics to prevent traveler's diarrhea generally should be discouraged, especially in light of high rates of antimicrobial resistance.

In selected patients (e.g., those who cannot afford a brief illness or have an increased susceptibility to infection), the use of rifaximin, which is nonabsorbable and well tolerated, is reasonable.

When stools are free of mucus and blood, early patient-initiated treatment of traveler's diarrhea with a quinolone 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.

Antimicrobial therapy for STEC/EHEC infection (the presence of which is suggested by bloody diarrhea without fever) should be avoided, since antibiotics may increase the incidence of HUS .