Escherichia Coli Infections

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Background

Escherichia coli is one of the most frequent causes of many common bacterial infections, including cholecystitis, bacteremia, cholangitis, 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 coli meningitis 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 abscesses. Escherichia coli liver abscess is seen in the image below.


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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.[1] Although 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 coli. E 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.


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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 arthritis, endophthalmitis, suppurative thyroiditis, sinusitis, osteomyelitis, endocarditis, 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.

History

Acute bacterial meningitis

Newborns with E coli meningitis present with fever and failure to thrive or abnormal neurologic signs. Other findings in neonates include jaundice, decreased feeding, periods of apnea, and listlessness.

Patients younger than 1 month present with irritability, lethargy, vomiting, lack of appetite, and seizures.

Those older than 4 months have neck rigidity, tense fontanels, and fever.

Older children and adults with acute E coli meningitis develop headache, vomiting, confusion, lethargy, seizures, and fever.

In rare cases, persons with a history of open CNS trauma or multiple neurological procedures develop S stercoralis hyperinfection.

Because patients who have undergone neurosurgery frequently have headaches, nuchal rigidity, and a decreased level of consciousness secondary to the surgery, signs may be difficult to interpret.

The differential diagnoses of acute E coli meningitis include sepsis, seizure disorder, brain abscess, ruptured aneurysm, and neonatal tetanus.

Pneumonia

Patients with E coli pneumonia usually present with fever, shortness of breath, increased respiratory rate, increased respiratory secretions, and crackles upon auscultation.

Findings include bronchopneumonia on chest radiography, commonly in the lower lobes. Many patients are intubated and have fever, an increased respiratory rate, and increased respiratory secretions.

The differential diagnoses of E coli pneumonia include congestive heart failure and pulmonary embolism. Other pneumonias caused by gram-negative bacilli are difficult to distinguish clinically.

Intra-abdominal infections

Patients with E coli cholecystitis or cholangitis develop right upper quadrant (RUQ) pain, fever, and jaundice. In severe cases, hypotension and confusion also develop. Cholecystitis manifests with fever (>102°F). Cholangitis manifests with fever (>102°F), shaking chills, and RUQ pain and can be complicated by hepatic abscess. Amebic liver abscess, Echinococcus cyst, and Klebsiella and Enterococcus infections are difficult to distinguish clinically. Anaerobes are observed in patients with diabetes and acute acalculous cholecystitis.

Patients with E coli intra-abdominal abscesses may have low-grade fever, but the spectrum of clinical presentations ranges from nonspecific abdominal examination findings to frank septic shock. Peritonitis manifests as localized pain with rebound and fever. The presentation ranges from low-grade fever with abdominal tenderness, weakness, malaise, and anorexia to hypoxemia and hypotension. The infection is usually polymicrobial with E coli and other gram-negative bacilli and anaerobes. The differential diagnoses include retroperitoneal hematoma and septic thrombophlebitis.

Enteric infections

Patients with E coli traveler's diarrhea (ie, watery nonbloody diarrhea; caused by enterotoxigenic E coli [ETEC] or enteroaggregative E coli [EAggEC]) may appear to be dehydrated. Traveler's diarrhea is observed in young healthy travelers to tropical countries and is watery diarrhea without polymorphonuclear (PMN) leukocytes. The differential diagnoses of E coli traveler's diarrhea include rotavirus infection, Norwalk virus infection, Salmonella infection, and Campylobacter diarrhea.

Patients with E coli childhood diarrhea (ie, watery nonbloody diarrhea; caused by EAggEC, enteroadherent E coli [EAEC], or enteropathogenic E coli [EPEC]) may also appear to be dehydrated. These infections produce a noninflammatory watery diarrhea observed especially in children. The differential diagnoses of E coli childhood diarrhea include Vibrio cholerae infection and Rotavirus infection.

In May, June, and July, 2011 an outbreak of gastroenteritis caused by Shiga-toxin–producing E coli was seen in Germany. The majority of patients were adults and 22% of the cases developed hemolytic–uremic syndrome The outbreak strain was typed as an enteroaggregative Shiga-toxin–producing E coli O104:H4, producing extended-spectrum beta-lactamase. The consumption of sprouts was identified as the most likely vehicle of infection. This outbreak was different as it was caused by EAggEC that produced a Shiga toxin and it exemplifies the threat posed by foodborne pathogens with their propensity to cause large common-source outbreaks.[2, 3]

Patients with E coli dysentery (caused by enteroinvasive E coli [EIEC] or enterohemorrhagic E coli [EHEC]) have fever, bloody diarrhea, and dehydration. Intestinal mucosa produces a significant inflammatory response. Clinically, patients with E coli dysentery present with fever and have blood and PMN leukocytes in their stool. The differential diagnoses of E coli dysentery include shigellosis and amebic dysentery.

Patients with E coli HUS (caused by EHEC) have fever, bloody diarrhea, dehydration, hemolysis, thrombocytopenia, and uremia requiring dialysis. Symptoms of E coli HUS range from asymptomatic to nonbloody diarrhea to bloody diarrhea, renal failure, microangiopathic hemolytic anemia, thrombocytopenia, and CNS manifestations. The differential diagnoses of E coli HUS include Shigella infections, Clostridium difficile enterocolitis, ulcerative colitis/Crohn disease, ischemic colitis, diverticulosis, and appendicitis.

Urinary tract infections

Acute E coli urethral syndrome manifests as low-grade fever and dysuria. Patients present with dysuria, increased frequency, and urgency, and they have colony counts. S saprophyticus infection is observed in 5-10% of cases, especially in sexually active women, associated with alkaline pH and microscopic hematuria. Less commonly, patients have Proteus mirabilis, Klebsiella, or Enterococcus infections. Approximately 15% of cases are culture-negative; these are due to Chlamydia trachomatis, Ureaplasma urealyticum, or Mycoplasma hominis infection.

Patients with symptomatic E coli UTI have dysuria and may have low-grade fever.

Patients with E coli pyelonephritis or complicated UTI present with localized flank or low back pain, high fever (>102°F), and urinary frequency and urgency. Findings also include rigors, sweating, headache, nausea, and vomiting. It can be complicated by necrotizing intrarenal or perinephric abscess, which manifests as a bulging flank mass or pyelonephritis that does not respond to antibiotics. Patients with diabetes or urinary tract obstruction can also develop bacteremia and septicemia. The differential diagnoses include psoas abscess appendicitis, ectopic pregnancy, and ruptured ovarian cyst.

Patients with E coli acute prostatitis or prostatic abscess have chills, sudden fever (>102°F), and perineal and back pain with a tender, swollen, indurated, and hot prostate. Acute prostatitis also manifests as dysuria, urgency, and frequent voiding. Some patients may have myalgia, urinary retention, malaise, and arthralgia. If the patient does not respond to antibiotics, consider prostatic abscess and confirm it with imaging studies. Treatment consists of open surgical or percutaneous drainage.

Patients with E coli prostatic abscess, which manifests as a complication of acute prostatitis, have a high fever despite adequate antimicrobial therapy and fluctuance of the prostate upon rectal examination.

The differential diagnoses of E coli acute prostatitis or prostatic abscess can include chronic bacterial prostatitis, which is usually asymptomatic; some patients may have frequency, dysuria, and nocturia with pain and discomfort in the perineal, suprapubic, penile, scrotal, or groin region. Also included are infected prostatic calculi, which can cause recurrent UTIs and should be surgically removed. Finally, nonbacterial prostatitis is also a differential diagnostic possibility and manifests as perineal, suprapubic scrotal, low back, or urethral tip pain.

Additionally, patients with E coli renal abscess present with fever, pleuritic chest pain secondary to diaphragmatic irritation, and flank pain, with or without a palpable abdominal mass.[2]

Physical

Acute bacterial meningitis

E coli is a common cause of meningitis in newborns and is associated most frequently with prematurity.

E coli meningitis can be acquired during birth or can develop secondarily after infection in another body site, such as in cases of omphalitis, upper respiratory tract infection, or infected circumcision wound.

In adults, E coli meningitis is not uncommon in those who have undergone multiple neurological procedures or who have had open CNS trauma.

Immunosuppressed patients receiving corticosteroid therapy and those with S stercoralis hyperinfection are also at risk for E coli meningitis.

Pneumonia

E coli pneumonia is often preceded by colonization of the upper respiratory tract (eg, nasopharynx).

Community-acquired E coli pneumonia has been reported in rare cases.

Intra-abdominal infections

Along with Enterococcus faecalis and Klebsiella species, E coli is one of the most common organisms associated with cholecystitis/cholangitis and intra-abdominal abscesses, as part of polymicrobial flora including anaerobes.

E coli cholecystitis/cholangitis manifests as the classic Charcot triad of fever, pain, and jaundice in 70% of cases. Fever is the most common finding (95%). RUQ pain and jaundice may be absent if no obstruction is present.

In late stages, hypotension, confusion, and renal failure are observed.

Liver abscess can develop as a complication of a E coli biliary tract infection.

The findings of E coli intra-abdominal abscesses are less conspicuous than those of diffuse peritonitis. The patient may have only low-grade fever, generalized malaise, and anorexia. In the postoperative patient who may have a distended and tender abdomen, clinical diagnosis of E coli intra-abdominal abscess may be difficult.

Enteric infections

Traveler's diarrhea usually occurs in persons from industrialized countries who visit tropical or subtropical regions and develop abdominal cramps and frequent explosive bowel movements 1-2 days after exposure to contaminated food or water.

E coli enterotoxin acts on the GI mucosa, leading to an outpouring of copious fluid from the small bowel.

The symptoms usually last 3-4 days and are self-limited.

Large fluid loss may result in dehydration.

EIEC infections are rare and manifest as bloody diarrheal stool containing PMN leukocytes. Patients usually have fever, abdominal cramping, and tenesmus lasting 5-7 days.

Childhood diarrhea is due to EPEC strains and usually occurs in underdeveloped countries or nursery outbreaks. The volume of diarrhea is less than that with ETEC strains, and no inflammatory cells are found in the diarrheal fluid. The child may experience fever, and diarrhea lasts longer than 2 weeks in some cases.

Infection with EHEC strains of the serotype 0157:H7 begin as watery diarrhea followed by grossly bloody stool without inflammatory PMN cells and results in HUS in 10% of cases, characterized by hemolysis, thrombocytopenia, uremia (possibly requiring dialysis), and death in some cases.

EAggEC and EAEC cause clinical illnesses that are not yet well characterized and are associated with persistent diarrhea in children.

Urinary tract infections

E coli is the leading cause of community-acquired and nosocomial UTI.

Females are predisposed to UTI because of their anatomy and changes during sexual maturation, pregnancy, and childbirth.

Young boys with posterior urethral valves are also predisposed to UTIs, as are elderly men with prostatic hypertrophy.

Other risk factors include catheterization or mechanical manipulation, obstruction, or diabetes.

Patients with E coli UTI present with a wide spectrum of symptoms, ranging from asymptomatic cystitis to pyelonephritis/perinephric abscess.

Urethral syndrome is a term used to describe symptoms of dysuria with colony counts less than 100,000 colony-forming units/mL of urine.

Uncomplicated E coli acute cystitis may manifest as low-grade fever, dysuria, and increased urinary frequency.

Acute pyelonephritis manifests as high-grade fever (>102°F) and costovertebral tenderness.

Acute prostatitis manifests as a sudden onset of fever and chills with perineal and low back pain.

Perinephric abscess may manifest as a bulging flank mass. GI symptoms such as nausea and vomiting are more likely in elderly persons. Patients with bacteremia secondary to an obstructed urinary catheter may present with decreased urine output.

Prostatic abscess can occur as a complication of acute prostatitis, notably in patients with diabetes mellitus, and should be considered in patients with acute prostatitis or UTI that is not improving with adequate antimicrobial therapy.

Other infections

E coli bacteremia can lead to septic shock, manifesting as hypotension and fever (in some cases, with hypothermia rather than fever). It may be complicated by uremia, hepatic failure, acute respiratory distress syndrome, stupor or coma, and death. Non–life-threatening E coli bacteremia may manifest as a sudden onset of fever and chills, tachycardia, tachypnea, and mental confusion. In cases of E coli UTI with urinary tract obstruction, bacteremia or septicemia may ensue.

A retrospective study determined risk factors for mortality in patients with fluoroquinolone-resistant E coli. Results show fluoroquinolone resistance, cirrhosis, and cardiac dysfunction independently predicted mortality.[4]

Several cases of E coli endophthalmitis have been reported in patients with diabetes who have UTI or pyelonephritis.[5]

Causes

Table. Differential Diagnoses of E coli Infection


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See Table

Laboratory Studies

All patients with suspected E coli infection should undergo routine CBC count with differential to evaluate for leukocytosis or a left shift.

Gram stain results determine if the organism is gram-negative, but findings do not distinguish among the other aerobic gram-negative bacilli that cause similar infectious diseases.

E coli is a gram-negative bacillus that grows well on commonly used media. It is lactose-fermenting and beta-hemolytic on blood agar. Most E coli strains are nonpigmented. The image below shows Escherichia coli on Gram staining.


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Escherichia coli on Gram stain. Gram-negative bacilli.

In the image below Escherichia coli can be seen growing on MacConkey agar.


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Escherichia coli culture on MacConkey agar.

Definitive diagnosis is based on the isolation of the organism in the microbiology laboratory from clinical specimens. Specimens may be blood, urine, sputum, or other fluids such as cerebrospinal, biliary, abscess, and peritoneal.

Recovery of the organism in contaminated sites, such as sputum and wounds, must be analyzed in the context of the patient's clinical state to determine if it represents colonization or infection. Recovery from sterile sites, such as the CSF, should be considered diagnostic of infection.

Lumbar puncture and a CSF culture positive for E coli establish the diagnosis of acute E coli meningitis; however, lumbar puncture is not justified in all babies presenting with sepsis. Indications for lumbar puncture include positive blood culture results, abnormal neurological signs, and detection of bacterial antigens in the urine.

Patients with pneumonia should undergo blood cultures and sputum Gram stain and culture. The results of a Gram stain of the sputum help to differentiate a good specimen (many PMN leukocytes, few squamous epithelial cells) from a bad specimen (few PMN leukocytes, many squamous epithelial cells). In addition, obtain the sputum culture before antibiotic therapy is initiated.

In enteric infections, the causative organism is suggested based on the clinical presentation and the characteristic of the patient's stool. Enterotoxigenic E coli (ETEC), enteropathogenic E coli (EPEC), enteroaggregative E coli (EAggEC), and enteroadherent E coli (EAEC) infections produce watery stools without inflammatory cells. Enteroinvasive E coli (EIEC) infection produces dysentery-type stools, and enterohemorrhagic E coli (EHEC) infection produces hemorrhagic-type stools.

In urinary tract infections, a urine dipstick test may be performed to rapidly determine if the patient has pyuria or bacteriuria based on the detection of leukocyte esterase and nitrites, respectively. Definitive diagnosis is based on urine culture results. Collect the specimen from a midstream clean void or from the catheter in patients with an indwelling Foley catheter. Colonization must be differentiated from infection based on urinalysis results. In cases of infection, pyuria is usually present.

Imaging Studies

In pneumonia, chest radiography or CT scanning is indicated.

In cholecystitis/cholangitis, ultrasonography or CT scanning of the RUQ is indicated.

In intra-abdominal abscess, abdominal and pelvic CT scanning is indicated; abscesses may be missed on sonograms.

In UTI, ultrasonography or CT scanning may be performed to help evaluate the kidneys and to look for any other source of abscess, stones, or obstruction.

Other Tests

E coli strains that cause diarrhea can be differentiated based on results from tests that are not widely used, such as DNA probes and polymerase chain reaction.

EPEC can be identified based on findings from serotyping, assays of adherence, and DNA probes. These tests are difficult to perform and not available widely. Also, results are difficult to interpret.

EIEC can be identified based on results from animal pathogenicity tests such as the Sereny test.

EHEC can be identified by looking for the major serotype involved, 0157:H7.

EHEC strains are cultured in a sorbitol MacConkey agar. Strains that are sorbitol-negative are then serotyped with 0157:H7 antisera.

EAEC and EAggEC are identified based on their adherence pattern on tissue culture cells. Serotyping is not useful.

Procedures

The following procedures may be indicated:

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 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, and rifaximin. They shorten the duration of diarrhea by 24-36 h. 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-d course of a fluoroquinolone, TMP/SMZ, or nitrofurantoin.

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

Patients with complex cases (eg, those with diabetes, >65 y, or recent history of UTI) are treated with a 7- to 14-d 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 d. 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 h, ultrasonography or CT scanning may be performed.

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

E coli sepsis requires at least 2 wk 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.[6] Remarkably, 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]

Doxycycline (Vibramycin)

Clinical Context:  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 DS, Septra)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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 (Amoxil, Trimox)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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, RedActiv, Flonorm)

Clinical Context:  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.

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]

Further Inpatient Care

The following are indicated:

Further Outpatient Care

Supportive care and rehabilitation should be provided to persons with meningitis who develop neurologic sequelae.

Inpatient & Outpatient Medications

Most severe E coli infections warrant hospitalization. These include meningitis, pneumonia, cholecystitis/cholangitis, intra-abdominal abscess, and some cases of complicated UTI and pyelonephritis.

In patients with pyelonephritis, a switch to oral medications should be made as soon as the patient is able to tolerate oral intake.

The duration of therapy depends on the type of infection.

In case of enterohemorrhagic E coli (EHEC) diarrhea, antibiotics are contraindicated and treatment is supportive and symptomatic in nature.

Complications

HUS may complicate EHEC infection. E coli meningitis in neonates usually results in neurological sequelae.

Prognosis

The prognosis depends on the specific diagnosis; therefore, no generalizations can be made.

Author

Tarun Madappa, MD, MPH, Attending Physician, Department of Pulmonary and Critical Care Medicine, Christus Spohn-Shoreline Hospital

Disclosure: Nothing to disclose.

Coauthor(s)

Chi Hiong U Go, MD, Assistant Professor, Department of Internal Medicine, Texas Tech University Health Science Center at Odessa

Disclosure: Nothing to disclose.

Specialty Editors

Larry I Lutwick, MD, Professor of Medicine, State University of New York Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Charles V Sanders, MD, Edgar Hull Professor and Chairman, Department of Internal Medicine, Professor of Microbiology, Immunology and Parasitology, Louisiana State University School of Medicine at New Orleans; Medical Director, Medicine Hospital Center, Charity Hospital and Medical Center of Louisiana at New Orleans; Consulting Staff, Ochsner Medical Center

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD, David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Eleftherios Mylonakis, MD, to the development and writing of this article.

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Escherichia coli liver abscess.

Escherichia coli right pyelonephritis.

Escherichia coli on Gram stain. Gram-negative bacilli.

Escherichia coli culture on MacConkey agar.

Escherichia coli liver abscess.

Escherichia coli right pyelonephritis.

Escherichia coli on Gram stain. Gram-negative bacilli.

Escherichia coli culture on MacConkey agar.

OrganismInd*UreaseMotilityGlu Ferm†Lact Ferm‡Sucr Ferm§Malt Ferm||Esc Hyd¶Hyd Sulf TSI#OxidaseOrn Dec**Lys Dec††
E coli+-++++/-+---+/-+
Klebsiella pneumoniae-+/--+++++---+
P mirabilis-+++----+-+-
Proteus vulgaris++++-+++/-+---
Pseudomonas aeruginosa-+/-++

(ox)‡‡

-----+--
Enterobacter aerogenes--++++++--++
Enterobacter cloacae--+++++---+-
Salmonella typhi--++--+-+--+
Citrobacter freundii+/--+++++-+/----
Serratia marcescens-+/-++-+++--++
*Indole

†Glucose fermentation

‡Lactose fermentation

§Sucrose fermentation

||Maltose fermentation

¶Esculin hydrolysis

#Hydrogen sulfite on TSI

**Ornithine decarboxylase

††Lysine decarboxylase

‡‡Oxidative