Escherichia coli (E coli) Infections


Background

Escherichia coli is one of the most frequent causes of many common bacterial infections, including cholecystitisbacteremiacholangitis, urinary tract infection (UTI), and traveler's diarrhea, and other clinical infections such as neonatal meningitis and pneumonia.

The genus Escherichia is named after Theodor Escherich, who isolated the type species of the genus. Escherichia organisms are gram-negative bacilli that exist singly or in pairs. E coli is facultatively anaerobic with a type of metabolism that is both fermentative and respiratory. They are either nonmotile or motile by peritrichous flagella. E coli is a major facultative inhabitant of the large intestine.

Pathophysiology

Acute bacterial meningitis

The vast majority of neonatal meningitis cases are caused by E coli and group B streptococcal infections (28.5% and 34.1% overall, respectively). Pregnant women are at a higher risk of colonization with the K1 capsular antigen strain of E coli. This strain is also commonly observed in neonatal sepsis, which carries a mortality rate of 8%; most survivors have subsequent neurologic or developmental abnormalities. Low birth weight and a positive cerebrospinal fluid (CSF) culture result portend a poor outcome. In adults, E colimeningitis is rare but may occur following neurosurgical trauma or procedures or complicating Strongyloides stercoralis hyperinfection involving the CNS.

Pneumonia

E coli respiratory tract infections are uncommon and are almost always associated with E coli UTI. No virulence factors have been implicated. E coli pneumonia may also result from microaspiration of upper airway secretions that have been previously colonized with this organism in severely ill patients; hence, it is a cause of nosocomial pneumonia. However, E coli pneumonia may also be community-acquired in patients who have underlying disease such as diabetes mellitus, alcoholism, chronic obstructive pulmonary disease, and E coli UTI. E coli pneumonia usually manifests as a bronchopneumonia of the lower lobes and may be complicated by empyema. E coli bacteremia precedes pneumonia and is usually due to another focus of E coli infection in the urinary or GI tract.

Intra-abdominal infections

E coli intra-abdominal infections often result from a perforated viscus (eg, appendix, diverticulum) or may be associated with intra-abdominal abscess, cholecystitis, and ascending cholangitis. Patients with diabetes mellitus are also at high risk of developing pylephlebitis of the portal vein and liver abscessesEscherichia coli liver abscess is seen in the image below.


Escherichia coli liver abscess. Escherichia coli liver abscess.

Intra-abdominal abscesses are usually polymicrobial and can be caused by spontaneous or traumatic GI tract perforation or after anastomotic disruption with spillage of colon contents and subsequent peritonitis. They can be observed in the postoperative period after anastomotic disruption. Abscesses are often polymicrobial, and E coli is one of the more common gram-negative bacilli observed together with anaerobes.

Cholecystitis and cholangitis result from obstruction of the biliary system from biliary stone or sludge, leading to stagnation and bacterial growth from the papilla or portal circulation. When bile flow is obstructed, colonic organisms, including E coli, colonize the jejunum and duodenum. Interestingly, partial obstruction is more likely than complete obstruction to result in infection, bacteremia, bactibilia, and gallstones.

Enteric infections

As a cause of enteric infections, 6 different mechanisms of action of 6 different varieties of E coli have been reported. Enterotoxigenic E coli (ETEC) is a cause of traveler's diarrhea. Enteropathogenic E coli (EPEC) is a cause of childhood diarrhea. Enteroinvasive E coli (EIEC) causes a Shigella -like dysentery. Enterohemorrhagic E coli (EHEC) causes hemorrhagic colitis or hemolytic-uremic syndrome (HUS). Enteroaggregative E coli (EAggEC) is primarily associated with persistent diarrhea in children in developing countries, and enteroadherent E coli (EAEC) is a cause of childhood diarrhea and traveler's diarrhea in Mexico and North Africa. ETEC, EPEC, EAggEC, and EAEC colonize the small bowel, and EIEC and EHEC preferentially colonize the large bowel prior to causing diarrhea.

Shiga toxin–producing E coli (STEC) is among the most common causes of foodborne diseases. This organism is responsible for several GI illnesses, including nonbloody and bloody diarrhea. Patients with these diseases, especially children, may be affected by neurologic and renal complications, including HUS. Strains of STEC serotype O157-H7 have caused numerous outbreaks and sporadic cases of bloody diarrhea and HUS.

Kappeli et al looked at 97 non-O157 STECstrains in patients with diarrhea and found that HUS developed in 40% of patients; serotype O26:H11/H was most often associated with this syndrome. [1Although strains associated with HUS were more likely to harbor STX 2 and EAE compared with those associated with bloody diarrhea , only 5 of the 8 patients with HUS had the STX2 gene; among the 3 patients with EAE -negative, STX2 -negative strains, only STX1 or STX1 and EHXA caused the HUS.

Urinary tract infections

The urinary tract is the most common site of E coli infection, and more than 90% of all uncomplicated UTIs are caused by E coli infection. The recurrence rate after a first E coli infection is 44% over 12 months. E coli UTIs are caused by uropathogenic strains of E coliE coli causes a wide range of UTIs, including uncomplicated urethritis/cystitis, symptomatic cystitis, pyelonephritis, acute prostatitis, prostatic abscess, and urosepsis. Uncomplicated cystitis occurs primarily in females who are sexually active and are colonized by a uropathogenic strain of E coli. Subsequently, the periurethral region is colonized from contamination of the colon, and the organism reaches the bladder during sexual intercourse.

Uropathogenic strains of E coli have an adherence factor called P fimbriae, or pili, which binds to the P blood group antigen. These P fimbriae mediate the attachment of E coli to uroepithelial cells. Thus, patients with intestinal carriage of E coli that contains P fimbriae are at greater risk of developing UTI than the general population. Complicated UTI and pyelonephritis are observed in elderly patients with structural abnormalities or obstruction such as prostatic hypertrophy or neurogenic bladders or in patients with urinary catheters. Escherichia coli right pyelonephritis is seen in the image below.


Escherichia coli right pyelonephritis. Escherichia coli right pyelonephritis.

E coli bacteremia is usually associated with UTIs, especially in cases of urinary tract obstruction of any cause. The systemic reaction to endotoxin (cytokines) or lipopolysaccharides can lead to disseminated intravascular coagulation and death. E coli is a leading cause of nosocomial bacteremia from a GI or genitourinary source.

Other infections

Other miscellaneous E coli infections include septic arthritisendophthalmitis, suppurative thyroiditis, sinusitis, osteomyelitisendocarditis, and skin and soft-tissue infections (especially in patients with diabetes).

Epidemiology

Frequency

United States

E coli is the leading cause of both community-acquired and nosocomial UTI. Up to 50% of females eventually experience at least one episode of UTI. E coli causes 12-50% of nosocomial infections and 4% of cases of diarrheal disease.

International

In tropical countries, EPEC is an important cause of childhood diarrhea. ETEC causes 11-15% of cases of traveler's diarrhea in persons visiting developing countries and 30-45% of cases of traveler's diarrhea among those visiting Mexico. EAggEC causes 30% of cases of traveler's diarrhea.

Mortality/Morbidity

E coli neonatal meningitis carries a mortality rate of 8%, and most survivors have neurological or developmental abnormalities.

The mortality and morbidity associated with E coli bacteremia is the same as that for other aerobic gram-negative bacilli.

Race

E coli infections have no recognized racial predilection.

Sex

E coli UTI is more common in females than in males because of differences in anatomic structure and changes during sexual maturation, pregnancy, and childbirth.

Men older than 45 years with prostatic hypertrophy are at an increased risk of UTI due to related bladder stasis.

Among neonates, E coli UTI is more common in boys than in girls, but circumcision reduces the risk.

Age

E coli is an important cause of meningitis in neonates. In adults, E coli meningitis is due only to open CNS trauma or neurosurgical procedures.

DDx

Differential Diagnoses

TREATMENT & MANAGEMENT

Escherichia coli (E coli) Infections Treatment & Management

Updated: Feb 11, 2019 
  • Author: Tarun Madappa, MD, MPH; Chief Editor: Michael Stuart Bronze, MD  more...
      
SECTIONS

Medical Care

Medical care of E coli infection is based on the site and severity of infection. In addition to antibiotics, provide supportive care, such as hydration, adequate oxygenation, and blood pressure support, if indicated.

Surgical Care

Surgical drainage/decompression may be indicated in patients with cholecystitis or cholangitis.

Surgical debridement may be indicated for those patients with intra-abdominal abscess.

In patients with urinary tract obstruction, such as prostatic hypertrophy, TURP may be indicated. In some cases, place ureteral stents for obstructed renal stones; however, remove these stents as soon as possible. Institute adequate surgical drainage for prostatic abscesses using transurethral unroofing or a perineal incision.

Diet

Food should be given to prevent malnutrition during an E coli diarrheal episode.

Activity

Activity can be continued as tolerated by the patient.

MEDICATION


Medication Summary

E coli meningitis requires antibiotics, such as third-generation cephalosporins (eg, ceftriaxone).

E coli pneumonia requires respiratory support, adequate oxygenation, and antibiotics, such as third-generation cephalosporins or fluoroquinolones.

E coli cholecystitis/cholangitis requires antibiotics such as third-generation cephalosporins that cover E coli and Klebsiella organisms. Empiric coverage should also include anti–E faecalis coverage.

For E coli intra-abdominal abscess, antibiotics also must include anaerobic coverage (eg, ampicillin and sulbactam or cefoxitin). In severe infection, piperacillin and tazobactam, imipenem and cilastatin, or meropenem may be used. Combination therapy with antibiotics that cover E coli plus an antianaerobe can also be used (eg, levofloxacin plus clindamycin or metronidazole).

E coli enteric infections require fluid replacement with solutions containing appropriate electrolytes. Antimicrobials known to be useful in cases of traveler's diarrhea include doxycycline, trimethoprim/sulfamethoxazole (TMP/SMZ), fluoroquinolones, rifaximin, and rifamycin. They shorten the duration of diarrhea by 24-36 hours. Antibiotics are not useful in enterohemorrhagic E coli (EHEC) infection and may predispose to development of HUS. Antimotility agents are contraindicated in children and in persons with enteroinvasive E coli (EIEC) infection.

Uncomplicated E coli cystitis can be treated with a single dose of antibiotic or 3-day course of a fluoroquinolone, TMP/SMZ, or nitrofurantoin.

Recurrent E coli cystitis (ie, >2 episodes/year) is treated with continuous or postcoital prophylaxis with a fluoroquinolone, TMP/SMZ, or nitrofurantoin.

Patients with complex cases (eg, those with diabetes, >65 years, or recent history of UTI) are treated with a 7- to 14-day course of antibiotics (eg, levofloxacin, third-generation cephalosporins, or aztreonam).

Acute uncomplicated E coli pyelonephritis in young women is treated with fluoroquinolone or TMP/SMZ for 14 days. Patients with vomiting, nausea, or underlying illness (eg, diabetes) should be admitted to the hospital. If fever and flank pain persist for more than 72 hours, ultrasonography or CT scanning may be performed.

Treat E coli perinephric abscess or prostatitis with at least 6 weeks of antibiotics.

E coli sepsis requires at least 2 weeks of antibiotics and identification of the source of bacteremia based on imaging study results.

McGannon et al found that antibiotics that target DNA synthesis, such as ciprofloxacin (CIP) and TMP/SMZ, showed increased Shiga toxin production, whereas antibiotics that target the cell wall, transcription, or translation did not. [6Remarkably, high levels of Shiga toxin were detected even when growth of O157:H7 was completely suppressed by CIP. In contrast, azithromycin significantly reduced Shiga toxin levels even when O157:H7 viability remained high.

Since the late 1990s, multidrug-resistant Enterobacteriaceae (mostly E coli) that produce extended-spectrum beta-lactamases (ESBLs), such as the CTX-M enzymes, have emerged within the community setting as an important cause of UTIs. These bacteria are resistant to the groups of antibiotics that are commonly used to treat these types of infections (penicillins, cephalosporins) and to antibiotics normally reserved for more severe infections (eg, fluoroquinolones, gentamicin).

The spread of CTX-M–positive bacteria considerably changes how the treatment of community-acquired infections is approached and limits the oral antibiotics that may be administered. This finding has major implications for treating individuals who do not clinically respond to first-line antibiotics. [7]

In one study, mortality following bacteremic infection caused by ESBL producing E coli was significantly higher than non–ESBL-producing E coli. These findings have serious implications for antibiotic prescription, as cephalosporins are ineffective treatment for many E coli infections. [8]

Infections due to ESBL-producing E coli have largely been regarded as a healthcare-associated phenomenon. However, reports of community-associated infections caused by ESBL-producing E coli have begun to emerge and this occurrence of community-associated infections due to extended-spectrum β-lactamase (ESBL)–producing Escherichia coli has been recognized among patients without discernible healthcare-associated risk factors in the United States. Most (54.2%) ESBL-producing strains that cause community-associated episodes belonged to ST131 or its related sequence types. Among these strains, all except one produced CTX-M–type ESBL, in particular CTX-M-15. [9]

Antibiotics

Class Summary

Empiric antimicrobial therapy must be comprehensive and cover all likely pathogens in the context of the clinical setting. However, given the broad use of antibiotics in hospitals, a study was performed to determine the relationship between hospital use of 16 classes of antibacterial agents and the incidence of quinolone-resistant E coli isolates. The results revealed that although the level of hospital use of quinolones influenced the incidence of quinolone resistance in E coli hospital isolates, the consumption of 2 other classes of antibiotics, cephalosporins and tetracyclines, is also associated with quinolone resistance. [10]

Recent data from the Canadian national surveillance study, CANWARD, revealed that 868 urine isolates of E coli collected from 2010-2013 were sensitive to fosfomycin using the Clinical and Laboratory Standards Institute (CLSI) agar dilution method, with minimum inhibitory concentrations (MICs) interpreted using CLSI M100-S23 (2013) criteria. The concentrations of fosfomycin inhibiting 50% (MIC 50 ) and 90% (MIC 90 ) of isolates were 1 or less and 4 μg/mL, respectivelyl; 99.4% of isolates were susceptible to fosfomycin. [11]

Doxycycline (Vibramycin, Adoxa, Doryx, Morgidox, Monodox)

Doxycycline inhibits protein synthesis and thus, bacterial growth, by binding to the 30S and possibly 50S ribosomal subunits of susceptible bacteria. It is used to treat traveler's diarrhea.

Trimethoprim/sulfamethoxazole (Bactrim, Bactrim DS, Septra DS, Sulfatrim)

Trimethoprim/sulfamethoxazole inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid. It is used to treat traveler's diarrhea for 5 days, uncomplicated UTI for 3 days, complicated UTI for 10-14 days, and acute prostatitis for 6-12 weeks.

Ciprofloxacin (Cipro)

Ciprofloxacin is a fluoroquinolone that inhibits bacterial DNA synthesis and, consequently, growth. It is used to treat mild-to-moderate UTI for 7-14 days, acute uncomplicated cystitis for 3 days, severe-to-complicated UTI for 7-14 days, infectious diarrhea for 5-7 days, and chronic bacterial prostatitis for 4-6 weeks.

Levofloxacin (Levaquin)

Levofloxacin is used for infections due to multidrug-resistant gram-negative organisms. It is used to treat community-acquired pneumonia for 7-14 days, acute pyelonephritis and complicated UTI for 10 days, and traveler's diarrhea for 5 days.

Amoxicillin (Moxatag)

Amoxicillin interferes with the synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria. It is used to treat uncomplicated UTI for 7 days and complicated UTI or pyelonephritis for 10-14 days.

Aztreonam (Azactam)

Aztreonam is a monobactam that inhibits cell wall synthesis during bacterial growth. It is active against aerobic gram-negative bacilli. It is used to treat complicated UTIs/pyelonephritis and bacteremia for 7-14 days, intra-abdominal infections for 14-21 days, and pneumonia for 14 days.

Ampicillin and sulbactam (Unasyn)

Ampicillin and sulbactam is a drug combination of a beta-lactamase inhibitor with ampicillin. It is used to treat intra-abdominal infections for 14-21 days.

Nitrofurantoin (Macrodantin, Macrobid, Furadantin)

Nitrofurantoin is synthetic nitrofuran and interferes with bacterial carbohydrate metabolism by inhibiting acetylcoenzyme A. It is used to treat uncomplicated UTIs for 7 days or for 3 days after urine is sterile.

Meropenem (Merrem IV)

Meropenem is a bactericidal broad-spectrum carbapenem antibiotic that inhibits cell wall synthesis. It is effective against most gram-positive and gram-negative bacteria. It is used to treat intra-abdominal infections for 14-21 days.

Ceftriaxone (Rocephin)

Ceftriaxone is a third-generation cephalosporin that arrests bacterial growth by binding to one or more penicillin-binding proteins. It is used to treat meningitis and bacteremia for 14-21 days and pneumonia, complicated UTI, or pyelonephritis for 14 days.

Piperacillin and tazobactam (Zosyn)

Piperacillin and tazobactam is an antipseudomonal penicillin plus beta-lactamase inhibitor. It inhibits biosynthesis of cell wall mucopeptide and is effective during the stage of active multiplication. It is used to treat intra-abdominal infections for 14-21 days.

Imipenem and cilastatin (Primaxin)

The imipenem and cilastatin combination is for treatment of multiple-organism infections in which other agents do not have wide-spectrum coverage or are contraindicated due to potential for toxicity. It is used to treat pneumonia and complicated UTI for 14 days, bacteremia for 7 days, and intra-abdominal abscess for 14-21 days.

Rifaximin (Xifaxan)

Rifaximin is a nonabsorbed (< 0.4%), broad-spectrum antibiotic specific for enteric pathogens of the GI tract (ie, gram-positive, gram-negative, aerobic, anaerobic). It is a rifampin structural analog, and it binds to the beta-subunit of bacterial DNA-dependent RNA polymerase, thereby inhibiting RNA synthesis. It is indicated for E coli (enterotoxigenic and enteroaggregative strains) associated with travelers' diarrhea.

Rifamycin (Aemcolo, Rifamycin SV MMX)

Oral nonabsorbable antibiotic that can be used to treat bacterial infections of the colon. Belongs to the ansamycin antibacterial drug class and acts by inhibiting the beta-subunit of bacterial DNA-dependent RNA polymerase, blocking one of the DNA transcription steps, which results in bacterial synthesis inhibition and consequently bacterial growth. It is indicated for traveler’s diarrhea caused by noninvasive strains of E coli not complicated by fever or blood in the stool.