Causative Organisms

 E. coli are members of the normal intestinal microbiota. Other enteric bacteria (Proteus, Enterobacter, Klebsiella, Morganella, Providencia, Citrobacter, and Serratia species) are also found as members of the normal intestinal microbiota but are considerably less common than E. coli. The enteric bacteria are sometimes found in small numbers  as part of the normal microbiota of the upper respiratory and genital tracts. The enteric bacteria generally do not cause dis ease, and in the intestine, they may even contribute to normal function and nutrition. When clinically important infections occur, they are usually caused by E. coli, but the other enteric bacteria are causes of hospital-acquired infections and occasionally cause community-acquired infections. The bacteria become pathogenic only when they reach tissues outside of their normal intestinal or other less common normal microbiota sites. The most frequent sites of clinically important infection are the urinary tract, biliary tract, and other sites in the abdominal cavity, but any anatomic site (eg, bloodstream, prostate gland, lung, bone, and meninges) can be the site of disease. Some of the enteric bacteria (eg, S. marcescens and E. aerogenes) are opportunistic pathogens. When the normal host defenses are inadequate—particularly in infancy or old age, in the terminal stages of other diseases, after immunosuppression, or with indwelling venous or urethral catheters— localized clinically important infections can result, and the bacteria may reach the bloodstream and cause sepsis.

Pathogenesis and Clinical Findings

 The clinical manifestations of infections with E. coli and the other enteric bacteria depend on the site of the infection and cannot be differentiated by symptoms or signs from processes caused by other bacteria.

A. E. coli

 1. Urinary tract infection (UTI)—E. coli is the most common cause of urinary tract infection and accounts for approximately 90% of first urinary tract infections in young women. The symptoms and signs include urinary frequency, dysuria, hematuria, and pyuria. Flank pain is associated with upper tract infection. None of these symptoms or signs is specific for E. coli infection. Urinary tract infection can result in bacteremia with clinical signs of sepsis.

Most of the urinary tract infections that involve the bladder or kidney in an otherwise healthy host are caused by a small number of O antigen types that have specifically elaborated virulence factors that facilitate colonization and subsequent clinical infections. These organisms are designated as uropathogenic E. coli. Typically, these organisms produce hemolysin, which is cytotoxic and facilitates tissue invasion. Strains that cause pyelonephritis express K antigen and elaborate a specific type of pilus, P fimbriae, which binds to the P blood group antigen.

Over the last decade, a pandemic clone, E. coli O25b/ ST131, has emerged as a significant pathogen. This organ ism has been successful largely as a result of its acquisition of plasmid-mediated resistance factors that encode resistance to β-lactam antibiotics (elaboration of extended spectrum β-lactamases), fluoroquinolones, and aminoglycosides (see the review by Johnson et al, 2010).

2. E. coli-associated diarrheal diseases—E. coli that cause diarrhea are extremely common worldwide. These E. coli are classified by the characteristics of their virulence properties, and each group causes disease by a different mechanism—at least six of which have been characterized. The small or large bowel epithelial cell adherence properties are encoded by genes on plasmids. Similarly, the toxins often are plasmid or phage mediated.

Enteropathogenic E. coli (EPEC) are an important cause of diarrhea in infants, especially in developing countries. EPEC adhere to the mucosal cells of the small bowel. Pathogenicity requires two important factors, the bundle forming pilus encoded by a plasmid EPEC adherence factor (EAF) and the chromosomal locus of enterocyte effacement (LEE) pathogenicity island that promote the tight adherence characteristic of EPEC (attachment and effacement). After attachment, there is loss of micro villi (effacement); formation of filamentous actin pedestals or cuplike structures; and, occasionally, entry of the EPEC into the mucosal cells. Characteristic lesions can be seen on electron micrographs of small bowel biopsy lesions. The result of EPEC infection in infants is characterized by severe, watery diarrhea, vomiting, and fever, which are usually self-limited but can be prolonged or chronic. EPEC diarrhea has been associated with multiple specific serotypes of E. coli; strains are identified by O antigen and occasionally by H antigen typing. A two-stage infection model using HEp-2 or HeLa cells also can be performed. Tests to identify EPEC are performed in reference laboratories. The duration of the EPEC diarrhea can be shortened and the chronic diarrhea cured by antibiotic treatment.

Enterotoxigenic E. coli (ETEC) are a common cause of “traveler’s diarrhea” and a very important cause of diarrhea in children less than 5 years of age in developing countries. ETEC colonization factors (pili known as colonization factor antigens [CFAs]) specific for humans promote adherence of ETEC to epithelial cells of the small bowel. Some strains of ETEC produce a heat-labile enterotoxin (LT) (molecular weight [MW], 80,000) that is under the genetic control of a plasmid and is closely related to cholera toxin. Its subunit B attaches to the GM1 ganglioside in the apical membrane of enterocytes and facilitates the entry of subunit A (MW, 26,000) into the cell, where the latter activates adenylyl cyclase. This markedly increases the local concentration of cyclic adenosine monophosphate (cAMP) after which ensues a complex cascade that involves the cystic fibrosis transmembrane conductance regulator. The end result is an intense and prolonged hypersecretion of water and chlorides and inhibition of the reabsorption of sodium. The gut lumen is distended with fluid, and hypermotility and diarrhea ensue, lasting for several days. LT is antigenic and cross-reacts with the enterotoxin of Vibrio cholerae, which has an identical mechanism of action. LT stimulates the production of neutralizing antibodies in the serum (and perhaps on the gut surface) of persons previously infected with enterotoxigenic E. coli. Persons residing in areas where such organisms are highly prevalent (eg, in some devel oping countries) are likely to possess antibodies and are less prone to develop diarrhea on reexposure to the LT producing E. coli. Assays for LT include (1) fluid accumulation in the intestines of laboratory animals, (2) typical cytologic changes in cultured Chinese hamster ovary cells or other cell lines, (3) stimulation of steroid production in cultured adrenal tumor cells, (4) binding and immunologic assays with standardized antisera to LT, and (5) detection of the genes that encode the toxins. These assays are done only in reference laboratories.

Some strains of ETEC produce the heat-stable enterotoxin STa (MW, 1500–4000), which is under the genetic control of a heterogeneous group of plasmids. STa activates guanylyl cyclase in enteric epithelial cells and stimulates fluid secretion. Many STa-positive strains also produce LT. The strains with both toxins produce a more severe diarrhea.

The plasmids carrying the genes for enterotoxins (LT, ST) also may carry genes for the CFAs that facilitate the attachment of E. coli strains to intestinal epithelium. Recognized colonization factors occur with particular frequency in some serotypes. Certain serotypes of ETEC occur worldwide; others have a limited recognized distribution. It is possible that virtually any E. coli may acquire a plasmid encoding for enterotoxins. There is no definite association of ETEC with the EPEC strains causing diarrhea in children. Likewise, there is no association between enterotoxigenic strains and those able to invade intestinal epithelial cells.

Care in the selection and consumption of foods potentially contaminated with ETEC is highly recommended to help prevent traveler’s diarrhea. Antimicrobial prophylaxis can be effective but may result in increased antibiotic resistance in the bacteria and probably should not be uniformly recommended. When diarrhea develops, antibiotic treatment effectively shortens the duration of disease.

Shiga toxin-producing E. coli (STEC) are named for the cytotoxic toxins they produce. There are at least two antigenic forms of the toxin referred to as Shiga-like toxin 1 and Shiga-like toxin 2. STEC has been associated with mild non-bloody diarrhea, hemorrhagic colitis, a severe form of diarrhea, and with hemolytic uremic syndrome, a disease resulting in acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia. Shiga-like toxin 1 is identical to the Shiga toxin of Shigella dysenteriae type 1, and Shiga-like toxin 2 also has many proper ties that are similar to the Shiga toxin; however, the two toxins are antigenically and genetically distinct. A low infectious dose (< 200 CFU) is associated with infection. Of the more than 150 E. coli serotypes that produce Shiga toxin, O157:H7 is the most common and is the one that can be identified most readily in clinical specimens. STEC O157:H7 does not use sorbitol, unlike most other E. coli, and is negative (clear colonies) on sorbitol MacConkey agar (sorbitol is used instead of lactose); O157:H7 strains also are negative on MUG tests . Many of the non-O157 serotypes may be sorbitol positive when grown in culture. Specific antisera are used to identify the O157:H7 strains. Tests for the detection of both Shiga toxins using commercially available enzyme immunoassays (EIAs) are done in many laboratories. Other sensitive test methods include cell culture cytotoxin testing using Vero cells and polymerase chain reaction for the direct detection of toxin genes directly from stool samples. Many cases of hemorrhagic colitis and its associated complications can be prevented by thoroughly cooking ground beef and by avoiding unpasteurized products such as apple cider. In 2011, the largest outbreak of hemorrhagic colitis attributed to a non-O157 serotype—namely, E. coli O104:H4—was related to consumption of contaminated sprouts in Germany. This organism had increased virulence characterized by enhanced adherence as well as the production of shiga-like toxins (see reference by Buchholz et al, 2011).

Enteroinvasive E. coli (EIEC) produce a disease very similar to shigellosis. The disease occurs most commonly in children in developing countries and in travelers to these countries. Similar to Shigella, EIEC strains are nonlactose or late lactose fermenters and are nonmotile. EIEC produce disease by invading intestinal mucosal epithelial cells.

Enteroaggregative E. coli (EAEC) causes acute and chronic diarrhea (>14 days in duration) in persons in developing countries. These organisms also are the cause of foodborne illnesses in industrialized countries and have been associated with traveler’s diarrhea and persistent diarrhea in patients with HIV. They are characterized by their specific patterns of adherence to human cells. This group of diarrheagenic E. coli is quite heterogeneous, and the exact pathogenic mechanisms are still not completely elucidated. Some strains of EAEC produce ST-like toxin (see earlier discussion on E. coli O104:H11); others a plasmid-encoded enterotoxin that produces cellular damage; and still others, a hemolysin. Diagnosis can be suspected clinically but requires confirmation by tissue culture adhesion assays not readily available in most clinical laboratories.

3. Sepsis—When normal host defenses are inadequate, E. coli may reach the bloodstream and cause sepsis. Newborns  may be highly susceptible to E. coli sepsis because they lack IgM antibodies. Sepsis may occur secondary to urinary tract infection and often the major clone associated with invasion is E. coli O25b/ST131.

4. Meningitis—E. coli and group B streptococci are the leading causes of meningitis in infants. Approximately 80% of E. coli from meningitis cases have the K1 antigen. This antigen cross-reacts with the group B capsular polysaccharide of N. meningitidis. The mechanisms of virulence associated with the K1 antigen are reviewed in the reference by Kim et al (2005).

B. Klebsiella–Enterobacter–Serratia; Proteus Morganella–Providencia; and Citrobacter

The pathogenesis of disease caused by these groups of enteric Gram-negative rods is similar to that of the nonspecific fac tors in disease caused by E. coli.

1. Klebsiella—Klebsiella species are present in the nasopharynx and feces of about 5% of normal individuals. The most commonly isolates species are K. pneumoniae and K. oxytoca. While K. pneumoniae may be isolated more frequently than K. oxytoca by clinical laboratories, both species are important human pathogens, known to cause community- as well as hospital-acquired pneumonia. K. pneumoniae can produce a lobar pneumonia with extensive hemorrhagic necrotizing consolidation of the lung, and has distinct clinical features, including its severity and propensity to affect the upper lobes, the production of “currant jelly” sputum as a result of the associated hemoptysis, and abscess formation. Klebsiella species also cause urinary tract infections, wound and soft tissue infections, and bacteremia/sepsis. Recently a particular clone of K. pneumoniae has emerged as a cause of community-acquired pyogenic liver abscess that is seen mostly among Asian males worldwide. This particular K1-encapsulated strain phenotypically appears hypermucoviscous when grown in culture. Klebsiella species rank among the top 10 bacterial pathogens responsible for hospital-acquired infections. Multilocus sequencing typing has identified global emergence of two particularly important clones. Sequence type 16 has elaborated extended spectrum β-lactamases resulting in resistance to a broad range of penicillins and cephalosporins (but not carbapenem antibiotics). ST 258 is a multidrug-resistant strain called a “carbapenamase producer” because it is resistant to all β-lactam antibiotics including the broad spectrum carbapenem agents. Typically, it is resistant to other antimicrobial agents as a result of acquisition of plasmids that carry multiple resistance genes.

Klebsiella granulomatis (formerly Calymmatobacterium granulomatis) causes a chronic genital ulcerative disease, granuloma inguinale, and is thought to be a sexually transmitted disease. Granuloma inguinale predominantly occurs in tropical regions (eg, the Caribbean, South America, and South-East Asia) and is a rare disease in the United States. The organ ism does not grow in standard culture in the laboratory; the diagnosis is based on the visualization of “Donovan bodies” in tissue smears or biopsy specimens (pleomorphic bacilli present in the cytoplasm of macrophages and neutrophils demonstrated by Giemsa or Wright’s stain). The recommended treatment regimen is azithromycin 1 g orally once per week (or 500 mg daily) for at least three weeks and until all lesions have completely healed. Alternative antimicrobial treatment regimens exist, using ciprofloxacin, doxycycline, or trimethoprim–sulfamethoxazole.

Two other Klebsiella species are associated with inflammatory conditions of the upper respiratory tract, but are relatively uncommon in the United States: K. pneumoniae subspecies ozaenae has been isolated from the nasal mucosa and is the cause of ozena (atrophic rhinitis), a fetid, progressive atrophy of mucous membranes. K. pneumoniae subspecies rhinoscleromatis causes rhinoscleroma, a destructive granulomatous disease of the nasal passages, but can extend to the pharynx, larynx, and even the trachea. Both diseases are more commonly seem in the tropical regions of the world, and appear to be spread by person-to-person transmission.

2. Enterobacter—Three species/complexes of Enterobacter— Enterobacter cloacae complex, E. aerogenes complex, and Enterobacter sakazakii (now in the genus Cronobacter)— cause the majority of Enterobacter infections. Many Enterobacter species are commonly found in the environment (eg, soil, water, and sewage), and E. aerogenes and E. cloacae also occur in various foods (eg, meat, dairy products, and vegetables), hospital environments, and the skin and intestinal tract of humans and animals. These bacteria ferment lactose, may contain capsules that produce mucoid colonies, and are motile. These organisms cause a broad range of hospital-acquired infections such as pneumonia, urinary tract infections, and wound and device infections. Most strains possess a chromosomal β-lactamase called ampC, which renders them intrinsically resistant to ampicillin and first- and second-generation cephalosporins. Mutants may hyper produce β-lactamase, conferring resistance to third generation cephalosporins. Like K. pneumoniae, some hospital-acquired strains have plasmids that make them multidrug resistant including the carbapenem class of antimicrobial agents.

3. Serratia—Serratia species common opportunistic pathogens as well as colonizers in hospitalized patients. Serratia marcescens is probably the most frequently isolated Serratia species by clinical laboratories. While Serratia species are typically transmitted from person to person, transmission via medical devices, intravenous fluids, and indwelling catheters has also been described. In children, the gastrointestinal tract often serves as a reservoir for infection. Some Serratia species produce a characteristic red pigment (prodigiosin). In S. marcescens pigment production may be an indicator of the strains environmental origin; however, only about 10% of the clinical isolates of S. marcescens produce this pigment. Most common sites of infection include the urinary tract, but S. marcescens also causes pneumonia, bacteremia, wound infections, bone and soft tissue infections, and endocarditis (the latter frequently in intravenous drug users). Treatment of infections due to S. marcescens is often difficult due to resistance to multiple antibiotics; S. marcescens is  resistant to penicillin, ampicillin, and first-generation cephalosporins because it harbors an inducible, chromosomal AmpC β-lactamase. Resistance to fluoroquinolones and trimethoprim–sulfamethoxazole has also been described. Because antibiotic susceptibility varies by strain, no empiric guidelines are available for treatment of infections due to S. marcescens.

 4. Proteus—Proteus species are widespread in the environment and are normal inhabitants of the human intestinal tract. The two species to most commonly produce infections in humans are P. mirabilis and P. vulgaris. Both species produce urease, resulting in rapid hydrolysis of urea with liberation of ammonia. Thus, in urinary tract infections with Proteus species, the urine becomes alkaline, promoting stone formation and making acidification virtu ally impossible. In addition, the rapid motility of Proteus may also contribute to its invasion of the urinary tract. The spot-indole test is useful for differentiation between the two most common Proteus species: P. vulgaris is indole positive, whereas P. mirabilis is negative. P. mirabilis causes urinary tract infections and occasionally other infections, such as bloodstream infection (frequently secondary due to a UTI) and respiratory tract infections. P. vulgaris is probably more frequently implicated in wound and soft tissue infections than UTIs.

Strains of Proteus vary greatly in antibiotic susceptibility. P. mirabilis is resistant to nitrofurantoin but most often susceptible to penicillins (eg, ampicillin and amoxicillin), trimethoprim–sulfamethoxazole, cephalosporins, aminoglycosides, and imipenem; P. vulgaris is generally more resistant to various antibiotics (specifically ampicillin, amoxicillin, and piperacillin; the most active antibiotics for P. vulgaris and other members of the group are aminoglycosides and broad-spectrum cephalosporins.

 5. Providencia—Providencia species (P. rettgeri, P. alcalifaciens, and P. stuartii) are members of the normal intestinal microbiota. All cause urinary tract infections and occasionally other infections and are often resistant to antimicrobial therapy.

6. Morganella—The genus Morganella consists of a single species, M. morganii. This organism is commonly found in the environment and in the intestinal tract of humans, mammals, and reptiles. It has been described as infrequent cause of nosocomial infections of the urinary tract and wounds; rare cases of bacteremia have also been reported. M. morganii is typically resistant to penicillins (eg, ampicillin and amoxicillin), and first- and second-generation cephalosporins; however, it is usually susceptible to broad spectrum cephalosporins, aminoglycosides, aztreonam, and imipenem.

7. Citrobacter—Citrobacter species can cause urinary tract infections, sepsis, respiratory tract infections, intraabdominal infections, and wound infections, principally among immunocompromised and/or debilitated hospitalized patients. In addition, Citrobacter koseri has been associated with meningitis in infants less than 2 months of age.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم الشؤون الفكرية يعلن مشاركة ممثلين من 18 دولة إفريقية في خدمة زائري الإمام العسكري (عليه السلام)

مصور في قسم إعلام العتبة العباسية المقدسة يحصد المركز الأول في مسابقة دولية

العتبة العباسية المقدسة تختتم مجالس العزاء بذكرى شهادة الإمام الحسن العسكري (عليه السلام)

مركز الكفيل يستأنف دوراته التدريبية في الإسعافات الأولية لمنتسبي العتبة العباسية المقدسة

المزيد

الآخبار الصحية

دون آثار جانبية.. زيت عشبة طبيعية قد يعالج القلق

"ليكانيماب".. علاج الزهايمر يطرح رسميا في السوق الألمانية

متى يجب تنظيف الأسنان في الصباح.. قبل أم بعد الإفطار؟

ارتفاع الوفيات.. منظمة الصحة تدق جرس الإنذار بشأن الكوليرا

المزيد

الآخبار التكنلوجية

أكبر مشروع طاقة رياح في نصف الكرة الجنوبي يحقق إنجازين جديدين

5 أمور لا تفعلها أثناء تشغيل مكيف سيارتك

ضوء إدارة المحرك: أسئلة مهمة لفهم عمله ومعانيه

"واتساب" يطلق خاصية جديدة لكتابة الرسائل بالذكاء الاصطناعي

المزيد

مواضيع ذات صلة

Rapidly Growing Nontuberculous mycobacteria (RGM)

Slow-growing Nontuberculous Mycobacteria

Mycobacterium Tuberculosis Complex

Anaerobic Gram-Positive and Gram-Negative Cocci

The Salmonellae

The shigellae

Antigenic Structure of Enterobacteriaceae

Gram-Negative Rods

Gram-Positive, non–Spore- Forming Bacilli

Gram-Positive, Spore Forming Bacilli

Morphology and Identification of Enterobacteriaceae

Clinical Findings of Enterococci