23 Gastrointestinal tract infections Flashcards
What is meaning of these terms -
Gastroenteritis
Dysentery
Enterocolitis
Gastroenteritis - nasuea/ vomiting/ diarrhoea usually due to enterotoxin in small bowel. Causes increased fluid/ electrolyte loss
Dysentery - inflammation of GI tract causing blood in stool - indicating invasive infection causing mucosal destruction. Causes pain, fever, abdominal pain
Enterocolitis - inflammation of both small and large intestine
Why is food poisoning a bad term?
Food poisioning correct if describing disease due to heavy metal, or toxin e.g botulism
Food-associated infection is better as organisms may be transported in via food (campylobacter), or can provide vessel to multiply within (salmonella)
What are host defenses against GI pathogens?
Saliva - lysosyme
Normal bacterial flora
Stomach acid
bile
Shedding epithelium
secretory IgA
Lymphoid tissue - Peyer’s patches
What are physiological outcomes from initial GI infection?
Local disease - e.g shigella/ amoebiasis causing diarrhoea
Systemic disease e.g fever, myalgia, jaundice
- spread - hepatitis A/ enteric fever
- toxin - cholera/ staph
E. Coli species can be grouped into six pathogtypes, based on mechanisms of pathogenicity.
What are their names?
Most E. coli species are part of normal GI flora
EPEC
ETEC
VTEC - sometimes termed STEC/ EHEC
EIEC
EAEC
DAEC
How does EPEC E. Coli cause disease?
Does not produce toxin
Has pili to bind to epithelial cells, leading to disruption of microvillus
How does ETEC E. coli cause disease?
Common cause Traveller’s diarrhoea
Bind to villi of small intestine - disrupting barrier
Produce enterotoxin - either heat labile HT or heat stabile ST
Heat-labile enterotoxin LT1 is similar to cholera toxin
Heat-stabile entertoxin activate guanylate cyclase activity causing increase cyclic guanosine monophosphate which results in increased fluid secretion
How does VTEC E. coli cause disease?
Notifiable disease
Binds to villi of small intestine - disrupting barrier
Produce a verotoxin which is similar to shiga-toxin, and causes direct damage to intestinal epithelium.
Also damages renal epithelium, as veroreceptors seen there
Toxin causes destruction of mucosa and haemorrhagic colitis. Can lead to haemolytic-uraemic syndrome
What is most common VTEC E.coli species?
O157:H7
How to identify case of HUS?
Usually children aged 0-5
Fever/ abdo pain/ vomiting diarrhoea which becomes bloody
Contact with farm animals
Microangiopathic haemolytic anaemia (Coombs’ test negative).
Thrombocytopenia.
Acute kidney injury - most common cause of childhood renal failure
How does VTEC toxin cause HUS?
Verotoxin 1 + 2
circulating toxin which binds to endothelial receptors, particularly in the renal, gastrointestinal and central nervous systems.
Thrombin and fibrin are deposited in the microvasculature. This occurs early in the disease, prior even to the development of HUS and may be why antibiotics confer no benefit.
Erythrocytes are damaged as they pass through partially occluded small vessels and subsequent haemolysis occurs.
Platelets are sequestered but without the cascade of clotting factors as in disseminated intravascular coagulation
What are investigations for HUS?
FBC and film: evidence of haemolysis, anaemia and thrombocytopenia. Raised white cell count and low platelet count are early indicators of development of HUS.
LDH raised
CRP raised
Clotting screen (reduced values may be seen during active HUS).
Stool culture: stool sample should be sent for culture and phage typing of the E. coli. Genes for virulence factors may be confirmed by polymerase chain reaction (PCR).
Urinalysis - haematuria
How to manage HUS?
Report to public health
Supportive management - may include dialysis
No evidence of antibitotics/ FFP helping
How does EIEC cause disease?
Attach to mucosa of large intestine
Invade cells by endocytosis
Lyse endocytic vacuole, multiply, spread to adjacent cells causing destruction.
Results in blood and mucus in stools
How does EAEC cause disease?
Attach to small intestine mucosa
Produces heat labile toxins
Which species of E.coli are more common in resource rich/ poor countries?
Poor/ traveller diarrhoea - EPEC/ ETEC
Rich - EHEC
What is treatment of E.coli diarrhoea? excluding HUS
Supportive
No role for antibiotics - antibiotics actually increase risk of HUS
E. coli bacteraemia will require treatment
Acute onset diarrhoeal illness within 1 day.
What are possible pathogens?
Bacillus cereus
Clostridium perfringens
S aureus enterotoxin - 30mins - 8hours
What are causes of bloody diarrhoea?
Amoebiasis
Campylobacter
Shigella
Yersinia entercolitica
EHEC/ EIEC
Which species of salmonella cause enteric fever?
After infection, people can carry typhoid providing ongoing source of infection e.g Typhoid Mary
Typhoidal Salmonella -
- Typhi
- Paratyphi A/B/C
Rest of species are known as non-typhoidal salmonella
How are salmonella species differentiated?
O antigen - cell wall
H antigen - flagella
Over 2000 serotypes classified as typhoidal/ non-typhoidal
O/H antigens also used to classify E. coli
What are sources of salmonella/ how is it spread?
Large animal reservoir in poultry/ dairy/ reptiles
Initial infection usually via contaminated food - faecal-oral spread
Then human-human spread occurs
What is path of salmonella through the body?
Ingestion
Absorbed by epithelial cells small itnestine
Penetrate to lamina propria in ileocaecal region
Macrophages confine infection to GI tract
Inflammatory response causes release of prostaglandins, which stimulate cAMP
This stimulates fluid secretion and diarrhoea
Salmonella usually causes mild self-limiting diarrhoea
Salmonella can become invasive and spread beyond small intestine
Who is at risk?
Immunocompromised
Elderly
Children
Sickle cell
What conditions are caused by invasive salmonella?
Fever is sign of systemic illness, and may require admission
Bowel perforation
Osteomyelitis
Pneumonia
Meningitis
Endocarditis
Cholecystitis - can form reservoir here
How to test for invasive salmonella?
Blood culture
Widal test - agglutination assay detecting antibodies ahainst O/ H antigens
Stool culture to confirm that salmonella has caused enteric infection
What is treatment for salmonella?
Usually self-limiting
Fluid replacement
No antibiotics, unless signs of invasion.
Azithromycin + ceftriaxone
Ciprofloxacin - resistance emerging
Ceftriaxone
Surgical intervention may be required if complications occur
If food handler, cannot work until three specimens of faeces have failed to grow salmonella
Vaccination live attenuated available for travellers - up to 80% protection
What is source/ transmission of campylobacter?
Large animal reservoir
Consumption of contaminated food - faecal-oral
Person-person spread is less common
Campylobacter has similar life cycle to salmonella.
Except it can cause bleeding of mucosal surface, and production of cytotoxins by C. jejuni
What clinical manifestations can occur?
Meningitis
Guillain-Barre
Endocarditis
IBD/ IBS?
What is treatment of campylobacter infection?
Usually self-limiting
If unwell/ fever -
Azithromycin
Ciprofloxacin - resistance emerging
V cholerae can live in free water. It has flagella so is motile
Common cause of infection in Asia/ Africa/ SA
How is it spread/source?
Contaminated water
Contaminated food
Shellfish grown in polluted estuaries
Person-person transmission rare
Natural disasters such as floods/ earthquakes can disrupt public health facilities and cause outbreaks
How are cholera species classifed?
Over 200 serogroups
Only these serogroups cause epidemic cholera -
O1 Classical
O1 El Tor - milder disease, but longer carriage
O139
What causes cholera symptoms?
Diarrhoea can be up to 1l/ hour
Enterotoxin
A subunit
B subunit
A subunit activates adenylate cyclase causing intracellular cAMP to rise, cause secretory diarrhoea - rice water
B subunit binds to eukaryotic cells
What is treatment of cholera?
Fluid/ electrolyte replacement
Acidosis - loss bicarbonate
Hypokalaemia - loss potassium
Hypovolaemic shock
All contribute to high mortality without treatment
Antibiotics for severe disease -
azithromycin
ciprofloxacin
Antibiotics also reduce carriage rate
Shigella can range from mild self limiting illness, or severe disease depending on species infecting.
Produces shiga toxin, which is similar to toxin produced by EHEC, damages intestinal epithelium.
What are names of species?
S sonnei - mild
S boydii - moderate
S flexneri - moderate
S dysenteriae - severe
Has no animal reservoir, so should be erradicated with good hygiene/ sanitation
What are symptoms of shigella?
Starts as water diarrhoea, and changes to bloody diarrhoea with mucus
Fever
Abdominal pain
Children more commonly affected
What is treatment of shigella?
Mostly self-limiting
Antibiotics for severe cases -
azithromycin
ciprofloxacin
Yersinia entercolitica is uncommon cause of diarrhoea.
What is major reservoir?
Contaminated/ undercooked pork
Yersinia entercolitica causes watery or bloody diarrhoea. Not routinely checked for on stool culture
What is incubation period?
What is duration of symptoms?
4-7 days - slightly longer than other pathogens
1-2 weeks
What are causes of travellers diarrhoea?
Most commonly enterotoxigenic E. coli (ETEC), enteroaggregative E. coli (EAEC)
Campylobacter
Salmonella
Which bacteria produce toxins, which cause disease when ingested?
B cereus
C perfringens
C botulinum
S aureus enterotoxin
Up to 50% of S. Aureus strains produce enterotoxin to cause symptoms.
Enterotoxin A is most common
TSST-1 toxic shock syndrome toxin is not food associated
How do they cause disease?
Bind to MHC class II molecules resulting in T-cell stimulation, leading to production of proinflammatory mediators
Causes symptoms within 3-6 hours
Causes vomiting, but not diarrhoea.
Recover in 24h
Enterotoxins possibly implicated in pathophysiology of IBD
C boutlinum produces exotoxin which is neurotoxic
Seven major toxins named A-G
How is infection transmitted/ reservoir?
Found in soil
Toxins ingested in canned/ reheated food
What are symptoms of botulism?
Toxins ingested, then absorbed by gut into bloodstream.
Reach peripheral nerve synapses which it blocks
Symmetrical descending flaccid muscle paralysis, beginning with cranial nerves causing blurred vision, swallowing difficulty, slurred speech.
This then leads to paralysis of respiratory and cardiac muscles
Three forms of botulism -
- food-borne
- infant
- wound
How are they different?
- food-borne - ingest toxin
- infant - ingest bacteria, which multiply in gut and produce toxin. Does not happen as get older, as host defences mature to destroy ingested pathogen
- wound - grow in wound
Clinical symptoms are all the same
What is treatment of botulism?
Mainly supportive - airway support. Time to recovery can be from 30-100 days
Anti-toxin - stops further toxin binding, but does not remove already bound toxin
Differential diagnosis for botulism?
blurry vision
dysphagia
slurred speech
Botulism
Descending form of acute inflammatory polyneuropathy.
Guillain-Barré syndrome.
Poisoning.
Myasthenia gravis.
How to diagnose botulism?
Toxin detection - PCR
Bioassay - take patient serum and inject into mice which are either protected with antitoxin/ not protected
Not practical to prevent food from being contaminated with botulism, aim to prevent spore formation.
How is this dose?
Maintain food at acid pH
Store food <4degC
Cook food thoroughly
Clostridium perfringens produces exotoxin which causes diarrhoea.
What happens if food inadequately cooked?
What other diseases does C perfringens cause?
Bacteria killed, but spores germinate releasing enterotoxin
Skin and soft tissue infection - gas gangrene
Bacillus cereus is widespread in soil, and contaminates many foods
What clinical syndromes can it cause?
Vomiting - due to ingestion of enterotoxin (heat-stable)
Diarrhoea - due to ingestion of bacteria, and production of enterotoxin (heat-labile) in gut
Clostridium difficile is most common cause of healthcare associated infection.
Antibiotics kill gut flora, which can then be re-colonised by other bacteria
C. difficile forms spore in environment
What exotoxins are produced?
Toxin A - increases intestinal permeability
Toxin B - cytotoxin causes inflammation, resulting in diarrhoea
How to diagnose C. difficile?
Symptoms normally occur 5-10 days after starting antibiotic therapy
Stool culture - check if bacteria present
GDH antigen test - check if bacteria present
PCR to check for toxin A/B presence
What are risk factors for C. difficile?
Prolonged/ multiple courses of antibiotics
Increasing age
Inpatient residence on ITU
Increasing duration of hospital stay; patients in long-term care facilities.
Immunocompromised patients.
PPI
Patient with suspected C. difficile
Apart from stool tests, how should you investigate patient?
WCC
Creatinine
Albumin - protein loss
AXR
Sigmoidoscopy
Surgical review
Stool chart
Fluid balance chart
What parameters make up C. diff severity score?
Score over 3 indicates severe CDI - increased mortality
WCC >15 Temp >38.5 5x stool motions per day Hypotensive Creatinine >50% above baseline Abdominal signs indicating colitis Radiological evidence of colonic dilation
What is management of C. diff first episode or first recurrence?
Isolate patient - until 48 hours after formed stool
Medication review - Abx/ PPI
Fluids
Metronidazole
- mild 400mg PO TDS 10-14 days
- severe 500mg IV TDS 10-14 days
Vancomycin oral/PR - increasing risk of vancomycin resistant enterococci
- mild - 125mg QDS 10-14 days
- severe - 500mg QDS 10-14 days
Colectomy if severe colitis
recurrence is termed as presenting within 8 weeks of first C. diff positive test
After first recurrence - same treatment
After second recurrence what is treatment?
Vancomycin 125 QDS 14 days 125 BD 7 days 125 OD 7 days 125 alternate days for 7 days
Or
Fidaxomicin 200mg BD for 10 days
What are options for third recurrence of C. difficile?
Vancomycin taper followed by rifaximin 400mg BD 14 days
IV immunoglobulin
Faecal transplant
Viral gastroenteritis clinically looks similar to bacterial/ parasitic causes
Norovirus is most common cause of diarrhoeal illness worldwide. Previously known as Norwalk-like virus, or winter vomiting diseases. Often associated with outbreaks e.g contaminated food, or sewage contaminated shellfish
What is genetic structure?
How many genotypes?
uneveloped
+ssRNA
6 genotypes
GI/ GII/ GIV cause infection in human
How to diagnose norovirus?
Why does infection not provide immunity?
PCR of stool
Noroviruses show high level of variability between strains, so infection does not provide cross-protection. Difficult to develop vaccine
Rotaviruses infect many mammals. Damage gut epithelium, resulting in fluid loss into lumen, and flattening of villi
What is nuclear material?
Who is usually affected?
How to diagnose?
dsRNA
Children under 2.
IgA in colostrom protects until 6 months old
Vaccine given at 8 weeks old
Ag detection via PCR or ELISA in children with diarrhoea <5
What other viruses can cause diarrhoea?
Sapovirus
Astrovirus
Adenovirus type 40/41
Coronavirus
Some viruses may be detected in stool e.g enterovirus, but do not cause diarrhoeal disease
H. pylori is gram negative spiral bacterium, causes peptic/ gastric ulcers/ MALT lymphoma
Produces urease that breaks down urea to ammonia and CO2, increasing pH to prevent against acid
How to diagnose?
Urea breath test
Faecal antigen test
Serology
Endoscopy/ biopsy - PCR
What is treatment of H. pylori?
7 day course, all meds BD
- PPI 40mg
- first line
amoxicillin 1g and clarithromycin 500mg
penicillin allergy -
clarithromycin 500 mg and metronidazole 400mg
What is pathophysiology whereby salmonella causes enteric fever?
Ingestion bacteria, penetrate gut mucosa via Peyer’s patches
Then reach intestinal lymph nodes, whereby they survive and multiply in macrophages. Lymph then drains into thoracic duct, then bloodstream
Salmonella then seeds to many organs causing disease. Particularly cells of reticuloendothelial cells e.g spleen, bone marrow, liver
Salmonella then enters gallbladder, where can survive long time as resistant to bile. Bacteria then re-enter intestinal system for second time, in larger numbers
This causes strong inflammatory response in Peyer’s patches leading to ulceration, and perforation
Chronic carriage defined as having salmonella in stool 1 year after infection
What are signs of enteric fever?
Can present with constipation.
Can present with rose spots on upper abdomen - maculopapular rash
Faget’s sign - high fever with bradycardia
What is differential diagnosis for Faget’s sign?
Brucellosis Chlamydia Colorado tick fever virus Coxiella burnetii Dengue Fever Drug fever Legionella Leptospirosis Leishmaniasis Mycoplasma Psittacosis Tularemia Typhoid fever Yellow Fever
Mostly intracellular organisms - physiology unclear
What is Lemierre’s syndrome?
Which organisms cause it?
Peritonsillar infection with involvement of jugular vein
Fusobacterium necrophorum most common. Also oral anerobes/ strep pyogenes/ eikenella can cause
What is treatment of Lemierre’s syndrome
Co-amoxiclav plus metronidazole
Add vancomycin if associated with device e.g central line
Patients with liver cirrhosis at risk of SBP, as they are immunocompromised. May not have symptoms, or raised WCC or fever
What are causative organisms?
Gram neg -
E. coli
Klebsiella
Gram pos-
Enterococci
Streptococci
Staphylococci
What are investigations for SBP?
Ascitic tap - WCC >250 cells/mm, culture
Blood cultures
What is treatment of SBP?
Tazocin or ceftriaxone (usually 5-7 days)
albumin on day 1 and 3
Ciprofloxacin prophylaxis after first episode of SBP
Peritoneal dialysis
Which organisms cause peritonitis in these patients?
Gram neg -
E. coli
Klebsiella
Pseudomonas
Gram pos-
Enterococci
Streptococci
Staphylococci
Staphylococci/ pseudomonas most common cause exit site infection
How to diagnose peritonitis in PD patients?
WCC >100/ml (0.1 x10 9/ litre) in PD fluid
Repeat on day 3 of treatment if not improving
Treatment of PD peritonitis?
Vancomycin 2g in 6 hour intraperitoneal (IP) dwell.
(1.5g if patient weighs <45kg).
And
Ciprofloxacin 500mg bd orally, or gentamicin
Then oral therapy once improved - ciprofloxacin/ rifampicin/ linezolid
14 days normal treatment duration, can be extended if slow to improve
May need PD tube change if treatment if unresponsive to antibiotics, or this is relapse from recently treated infection, or if fungal/ pseudomonal infection
PD dialysis
What is treatment of exit line infection?
Flucloxacillin 500mg QDs for a minimum of 2 weeks (continue until resolution).
or
Rfampicin 300mg BD
or
Ciprofloxacin 500mg BD - also has pseudomonal activity
