Escherichia coli

• E.coli causes UTI and gm negative rod sepsis. E.coli causing UTI is the patients own colonic flora that colonizes urogenital area.

• It is also an important cause of neonatal jaundice. It is the organism that is present in the mothers birth canal.

• It causes traveller’s, watery diarrhea. It spreads through ingested food/water contaminated with human feces.

E.coli are straight gm negative rods.Vibrio, Campylobacter, Helicobacter are

curved gm negative rods.They are the most abundant facultative

anaerobes in the colon and feces, yet greatly outnumbered by the obligate anaerobes (Bacteroides).

E.coli ferment Lactose.They possess all the three antigens, Flagellar

(H antigen), the capsular (K antigen) and the cell wall antigen (O antigen).

About a 1000 antigenic serotypes of E.coli known.

O55 and O111 cause neonatal diarrhea.O157 is an enterohemorrhagic E.coli.

Pathogenesis:The pili, the capsule, endotoxin and the three

exotoxins can all play a role in the pathogenesis of disease caused by E.coli.

In the intestinal tract infections, the organism binds to the cells of the jejunum and ileum by means of pili.

Enterotoxigenic strains can produce toxins.

• The toxins of E.coli may be Heat labile or heat stable.

• The heat labile toxin acts by stimulating adenylate cyclase. They act by ADP-ribosylating the Gs protein.

• The adenylate cyclase increases the cAMP levels which in turn activates a protein kinase that phosphorylates ion transporters in the cell membrane.

• Phosphorylated Ion transporters export ions, causing outpouring of fluids, potassium and chloride ions into the lumen of the gut, causing watery diarrhea.

The heat stable toxins are of two kinds.One, that is non-invasive, do not invade

intestinal mucosa, and do not cause inflammation.

They cause watery, non-bloody diarrhea.Another heat stable toxin is the Shiga toxin

produced by certain strains of E.coli (O157:H7).

• They invade the epithelium of large intestines causing bloody diarrhea. Inflammatory cells like Neutrophils can be found in the stool sample of such cases.

• The exotoxin, Shiga toxin, removes an adenine from the 28S ribosomal RNS, thereby stopping protein synthesis.

• Shiga toxin is encoded by a temperate lysogenic phage.

• Also called Verotoxin as it has cytopathic effect on vero(monkey) cells.

• The bloody diarrhea outbreak is usually after eating uncooked meat, hamburgers etc…

• A life threatening complication called Hemolytic-Uremic syndrome (HUS) can ensue, when the shiga toxin enters the blood stream.

• The Shiga toxin binds to the receptors on the endothelium surface of blood vessels and on the kidney epithelium

• The capillary damage causes death and lysis of the blood cells passing through them. These distorted, fragmented red cells called Schistocytes can be seen on the blood smear.

• Thrombocytopenia results when the platelets adhere to the damaged endothelium.

• Death of kidney cells lead to renal failure.• All this results in hemolytic anemia, thrombocytopenia

and acute renal failure.

The Capsule and the Endotoxin of E.coli play a prominent role in the pathogenesis of Systemic rather than intestinal tract disease.

Capsular polysaccharide interferes with phagocytosis and can cause neonatal meningitis. These usually have the K1 antigenic serotype.

• The endotoxin (LPS) of E.coli carry several characteristic features of fever, hypotension and DIC.

• Certain O serotypes of E.coli cause UTI. These are known as Uropathic strains.

• They are characterized by pili with adhesion proteins that bind to specific receptors on UT-epithelium.

• Their motility may assist them to ascend the urethra – bladder – ureter and into the kidneys.

• Clinical findings:

• In diarrhoea of the Enterotoxigenic and enterohemorrhagic9EHEC) already discussed.

• E.coli is the leading cause of community acquired UTI.• They occur primarily in women, because of short

urethra, proximity of urethra to the anus and colonization of vagina by the fecal flora.

• Also a frequent cause of mosocomial UTI, associated with indwelling urinary catheters.

• If only the bladder is involved, the disease is Cystitis, with symptoms of pain, and frequency of urination.

• The involvement of kidneys is Polynephritis with fever, chills and flank pains.

E.coli also a major cause of neonatal sepsis and meningitis along with group B streptococci. It colonizes the vagina of about 25% of pregnant women.

• Lab Diagnosis:

• McConkeys agar- Lactose fermenters, red colonies.

• On EMB give the characteristic green sheen.• Differentiated from other lactose fermenters as

it produces indole from Tryptophan, decarboxylates Lysine, Uses acetate as the only source of carbon and is motile.

• E.coli O157:H7 do not ferment Sorbitol. Other strains do.

• Isolation of E.coli not normally done.

• Treatment:

• Depends on the site of the disease and the resistance pattern of a specific isolate.

• In uncomplicated lower UTI: oral Trimethoprim-sulfamethoxazole or oral penicillin (ampicillin) for 1-3 days.

• In E.coli sepsis: treatment is with parenteral antibiotics like third generation Cephalosporin such as Cefotaxime, with or without an aminoglycoside such as Gentamicin.

• For neonatal meningitis: combination of Ampicillin and Cefotaxime.

• No antibiotics in Diarrhea. Rehydration is all that is necessary.

Prevention:Remove or avoid pre disposing cause.Cranberry juice, prevents the binding of pili

to the bladder epithelium.

SalmonellaCauses Enterocolitis : most common causeCauses Enteric fever such as Typhoid fever.Causes septicemia with metastatic infections

such as Osteomyelitis.

• Salmonella do not ferment lactose. Hydrogen sulfide negative.

• O, H and Vi antigens for taxonomic and epidemiological purposes.

• O antigens divide into groups from A-I.• H antigens are of 2 forms: Phase 1 and phase 2. Only

one of the two are synthesized at one time.• Vi (capsular) antigens are antiphagocytic and an

important virulent factor for S.typhi(typhoid fever). Also useful in serotyping S.typhi.

• There are many approaches to name Salmonella. Dividing into 3 species(EWING), naming after the city where isolated(Kaufmann and White) and Based on relatedness determined by DNA hybridization.

Clinically, Salmonella divided into 2 distinct categories:

Typhoidal species causing Typhoid fever like S.typhi and S.paratyphi.

Non-typhoidal species causing diarrhea(enterocolitis) and metastatic infections (osteomyelitis) like S.enteritidis and S.chloraesuis (metastatic infections).

• Pathogenesis:

• Enterocolitis is characterized by invasion of epithelial and sub-epithelial tissue of small and large intestine.

• Results in inflammation and diarrhea.• A polymorphonuclear(PMN) leucocytes limit the

infection to the gut and the adjacent mesenteric lymph nodes.

• Bacteremia is infrequent.• Infectious dose is large unlike Shigella.Gastric

acid is an important host defense.

• Typhoid and other Enteric fevers:

• Infection begins in small intestines but few gastrointestinal symptoms occur.

• Organisms enter and multiply in the mononuclear phagocytes of Peyers patches and spread to the phagocytes of the liver, gall bladder and spleen.

• This leads to bacteremia associated with onset of fever and other symptoms caused by the endotoxin.

• Survival of the organisms in the phagosomes is the striking feature of the disease. This is also the cause for invasion of the gall bladder and the carrier state.

• Septicemia:

• Septicemia accounts for 4-10% of salmonella infections, especially in patients with underlying disease such as sickle cell anemia, cancer or a child with enterocolitis.

• Septic course is more indolent than other gm neg. rods.• Bacteremia results in the seeding of many organs with

osteomyelitis, pneumonia and meningitis resulting.• Previously damaged tissues such as infarcts and

aneurysms(aortic aneurysm) most frequent site for metastatic abscesses.

• Sal. also important cause of vascular graft infections.

S.typhi transmitted only by humans, but with animals/human reservoir.

Chronic carrier state is common and infectes individuals actively secrete organisms

Animal source is poultry, eggs and undercooked meat.

• Clinical findings:• Enterocolitis:• Incubation period 12-48 hours with nausea and

vomitting followed by abdominal pain and diarrhea, mild to severe, with or without blood.

• Disease is self limiting, except in HIV cases with low CD4 cells, can cause severe diarrhea and metastatic infections.

• S.typhimurium, most common cause of enterocolitis.

• Typhoid fever:• Caused by S.typhi• Enteric fever caused by S,paratyphi A,

B(S.schottmulleri) and C(S.hirschfeldii).• Onset of illness is slow with fever and

constipation rather than vomitting and diarrhea.• Fever and bacteremia results. Bacteremia

becomes sustained after first week, with high fever, delirium, tender abdomen and enlarged spleen.

• Rose spots(rose colored macules on the abdomen) associated with typhoid fever.

Leucopenia and anemia often seen.LFT abnormalindicating hepatic involvement.Disease begins to resolve by the third week.Complications like intestinal hemorrhage or

perforation can occur.About 3% become chronic carriers, carrier

state high among women especially with previous gall bladder disease or gall stones.

Septicemia:Often caused by S.choleraesuis.Symptoms begin with fever with little or no

enterocolitis and proceed to focal symptoms associated with bones, lungs or meninges.

Lab diagnosis:Enterocolitis / Carrier state : organisms

isolated from stool sample.Enteric fever: blood culture during first two

weeks of illness.Bone marrow cultures often positive in

Septicemia cases.

• McConkeys/EMB- lactose non fermenters.• TSI: Acid butt / alkaline slant / Hydrogen sulfide

positive with gas.• S.typhi do not produce gas, with little hydrogen

sufide.• Urease negative to distinguish from Proteus

showing similar results on TSI.• Based on O- antigen Slide agglutination test, Sal.

Isolate grouped into A B C D E.• It is a notifiable disease.• In enteric fever and sepsis WIDAL test for

Antibody titers against O and H antigen

• Treatment:

• Enterocolitis:• Usually self limiting. Fluid and electrolyte

replacement may be required.• Antibiotics indicated only in neonates, or persons with

chronic diseases at risk of septicemia or disseminated abscesses.

• Plasmid related antibiotic resistance common. Antibiotic sensitivity tests may be necessary.

• For Septicemia with metastatic infection and Typhoid fever: Either Ceftriaxone or Ciprofloxacin.

• Ampicillin or Ciprofloxacin for chronic carriers of S.typhi

• Focal abcesses should be drained whenever possible.

• Prevention:

• 2 vaccines available, but limited (50-80%) immunity against S.typhi.

• Contains the Vi capsular polysaccharide given intramuscularly.

• Contains a live attenuated strain of S.typhi given orally.

• Conjugate vaccine of Vi polysaccharide coupled with a carrier protein, is immunogenic and safe for kids.

• Water supply should be adequately chlorinated and food cooked and milk pasteurized properly and to check infection through eggs.