C.DIFF, INCONTINENCE, MEGACOLON, ISCHAEMIC COLITIS Flashcards
Describe the characteristics of c.diff?
Gram positive
Rod shaped
Obligate anaerobes
Spore-forming
Toxin producing
In what percentage of adults is c.diff present as a commensalism organism?
2% healthy adults
7% pt with long term care facilities
Up to 26% in inpatient populations
(Many infants have c.diff without having the disease)
What are the 2 important strains of c.diff?
Toxigenic 80%
Nontoxigenic 20%
What is toxigenic c.diff?
Toxigenic produces and releases exotoxins A and B. It causes disease
Nontoxigenic cannot produce exotoxins and so colonises the colon without causing disease
What proportion of antibiotic-associated colitis is caused by c.diff?
20-30%
Whats the pathogenesis of c.diff infections?
Antibiotics disrupt the normal colonic microbiota, which allows toxigenic strains of CD to multiply and release toxins. These damage colonocytes and causes colitis.
TcdA - destroys cytoskeleton within an intestinal cell = damaged intestinal tissue becomes porous = strong inflammatory response
TcdB - enters cells, including neutrophils and causes cellular apoptosis = pseudomembranous colitis
More virulent strains of c.diff are resistant to certain antibiotics, providing a survival advantage
How is c.diff transmitted?
CD can release spores from asymptomatic or symptomatic carriers into the environment via faecal-oral route
What is pseudomembranous colitis?
swelling or inflammation of the large intestine (colon) due to an overgrowth of Clostridioides difficile (C difficile) bacteria
Where is c.diff found in the environment?
In deep compact soil
When they feel the stress of fresh oxygenated air they produce spores
What are the risk factors of c.diff infection?
Antibiotic use
Age >65
Hospitalisation
Severe underlying co-morbidities
Gastric acid suppression e.g. PPI use
Enteral feeding
Obesity
GI surgery
Chemotherapy
Which antibiotics pose the highest risk for CDI?
fluoroquinolones, clindamycin, and broad-spectrum penicillins and cephalosporins.
(Also: using multiple antibiotics or prolonged duration of antibiotics)
Why do antibiotics increase the risk for c.diff infection?
They cause an antibiotic-related loss of gut microbial communities that protect against gut infection, thereby facilitating the germination and vegetative growth of the c.diff when it enters the gut of vulnerable people
What are the clinical features of c.diff?
Watery diarrhoea (+/- a small amount of blood)
Abdominal pain
Anorexia
Nausea
Fever
Haemodynamic instability and severe systemic symptoms e.g. low GCS, oligouria if severe!
How is diarrhoea defined?
passage ≥3 loose bowel motions within 24 hours
Outline how the severity of c.diff colitis is staged?
Mild: diarrhoea without systemic features. Typically ≤ 3 bowel motions. WCC normal
Moderate: 3-5 bowel motions per day. Raised WCC but < 15 x109/L
Severe: WCC > 15 x109/L, rising creatinine (e.g. >133 umol/L), fevers > 38.5º, evidence severe colitis (abdominal or radiographic signs), bowel motions less reliable.
Fulminant: hypotension and shock, partial or complete ileus, toxic mega colon, CT evidence of severe disease.
How are acute and chronic diarrhoea distinguished?
Acute - < 14 days
Persistent diarrhoea >14 days
Chronic - >4weeks
How is c.diff diagnosed?
Bloods - FBC, BG, U&E, LFT, bone profile, lipase, cultures, venous blood gas (lactate and WCC raised)
Stool testing - NAAT and EIA, microculture&sensitibity, OCP, virology, FIT
Plain film abdominal radiograph
CT abdomen and pelvis
Endoscopy - pseudomembranous colitis
In a c.diff colitis, what will you see on a plain film abdominal radiograph?
Mucosal wall thickening and bowel dilatation
What is NAAT?
Nucleic acid amplified test
A PCR assay that allows detection of the genes specific to the c.diff toxins
What is EIA?
Enzyme immunoassay - detects enzymes or toxins produced by the c.diff strains
What enzymes and toxins does Enzyme immunoassay detect?
Glutamate dehydrogenase
Toxins A and B
Whats the problem with a positive test for glutamate dehydrogenase antigen?
It’s not necessarily indicative of active infection, simply that the patient is a carrier of the pathogen
What are the complications of c.diff infection?
Multiple relapses
Dehydration
Toxic megacolon
Ileus
Colon perforation
Intussusception
Pneumatosis
Ascites
Sepsis
Splenic abscess
Osteomyelitis
why can c.diff cause toxic megacolon?
inflammatory changes that penetrate into the muscularis propria resulting in neural injury, altered motility and dilation
What is pneumatosis intestinalis?
Presence of gas within the wall of the small or large intestine
What is protein losing enteropathy?
when albumin and other protein-rich materials leak into your intestine
What are the causes of protein losing enteropathy?
IBD
Congenital heart defect
Idiopathic ulcerative jejunoileitis
Infection
Neoplasm
Sarcoidosis
Amyloidosis
SLE
Zollinger-Ellison syndrome
Eosinophilia gastroenteritis
Infections e.g. c.diff
Coeliac disease
Common variable immunodeficiency
Primary intestinal lymphangectasia
What does pseudomembranous colitis look like on endoscopy?
Elevated yellow-white nodules or plaques that form pseudomembranous on mucosal surface of the colon
What drugs should be reviewed/stopped when a pt is positive for c.diff infection?
Antibiotics
Proton pump inhibitors
Medicines with GI activity or adverse effects e.g. laxatives
Meds that may cause problems if people are dehydrated - NSAIDs, ACE, ARBs, diuretics
How is c.diff prevented in hospitals?
Isolate and initiate contact precautions for suspected or confirmed CDI
Confirm CDI in pt and report test results immediately to clinical care providers and infection control personnel
Perform environmental cleaning daily including using a c.diff sporicidal agent
Hand washing with soap and water
Using appropriate PPE
Develop infrastructure to support CDI prevention
Engage the facility antibiotic stewardship programme
Whats the 2-step testing system recommended for c.diff infections?
Step 1 - a highly sensitive screening test e.,g. GDH EIA or NAAT or PCR with positive samples
Step 2 - highly specific testing with toxin A/B EIA
What are the risk factors for severe c.diff associated disease?
Age
Peak leukocytosis
Elevated blood creatinine
What proportion of pt with c.diff associated disease will experience a further episode or recurrence of CDI after initial treatment?
25%
Whats the difference between relapse and re-infection?
Relapse occurs early after symptoms resolution and is more likely to be with the same strain of c.diff
Re-infection occurs at a later time point and is more likely to be a different strain
What are the factors associated with an increased risk of CDI recurrence?
Age >65
Female
Raised leukocyte count
Multiple comorbidities
Length of hospital admission
Nursing home residence
Continued use of antibiotics for non-CDI indications
What is post-infectious IBS?
When IBS symptoms arise following exposure to acute gastroenteritis - abdominal discomfort, bloating and diarrhoea
What proportion of those with c.diff associated disease will experience post-infectious IBS?
22%
Why should antimotility agents be avoided in c.diff associated disease?
It could precipitate toxic megacolon by slowing the clearance of c.diff toxins from the intestine
What is the SIGHT protocol for managing infectious diarrhoea?
Suspect that a case may be infective where there is no clear alternative cause for diarrhoea
Isolate the patient and consult with the infection prevention and control team while determining the cause of the diarrhoea
Gloves and aprons for all contacts with pt and environment
Hand washing with soap and water should be carried out before and after each contact
Test the stool using a 2-step testing system
How should you manage a first episode non-severe CDI?
All patients: correct fluid losses, VTE prophylaxis, nutritional support, stop laxatives, stop antibiotics unless necessary, review need for PPI, stop anti-motility drugs (codeine/loperamide) and consider other causes of diarrhoea.
Oral metronidazole 400mg TDS for 10-14 days or oral vancomycin 125mg QDS for 10 days
How should you manage a recurrent non-severe CDI?
All patients: correct fluid losses, VTE prophylaxis, nutritional support, stop laxatives, stop antibiotics unless necessary, review need for PPI, stop anti-motility drugs (codeine/loperamide) and consider other causes of diarrhoea.
If <12 weeks since symptom resolution give oral fidaxomicin for 10 days. If >12 weeks then give oral vancomycin or oral fidaxomicin for 10 days
More than 2 episodes then seek infection specialist advice - consider FMT, bezlotoxumab or IVIG. Consider a diagnosis of post-infectious IBS
How should you manage life-threatening c.diff infection?
All patients: correct fluid losses, VTE prophylaxis, nutritional support, stop laxatives, stop antibiotics unless necessary, review need for PPI, stop anti-motility drugs (codeine/loperamide) and consider other causes of diarrhoea.
Oral vancomycin 500mg QDS and IV metronidazole 500mg TDS
Seek specialist advice - IVIG or FMT
What is FMT?
Fecal macrobiotic transplant
the process of transferring fecal bacteria and other microbes from a healthy individual into another individual. FMT involves restoration of the colonic microflora by introducing healthy bacterial flora through infusion of stool via colonoscopy, enema, orogastric tube, or by mouth in the form of a capsule containing feces from a healthy donor, which in some cases is freeze-dried.
What are the side effects of FMT?
Sepsis
Fever
SIRS-like syndrome
Exacerbation of IBD
Mild GI distress - flatulance, diarrhoea, irregular bowel movements, abdo pain etc…
What is IVIG?
Intravenous immune globulin
Giving antibodies IV - contains anti-toxin antibodies against c.diff toxins
When is FMT indicated in c.diff infections?
Refractory CDI or recurrent CDI i.e. a relapse of CDI symptoms within 2-8 weeks of successful treatment
What is megacolon?
An abnormal dilation of the colon not caused by mechanical obstruction
>12cm caecum
>6.5cm in rectosigmoid region
>8cm ascending colon
<6cm in transverse colon
What can cause megacolon?
Congenital or aganglionic megacolon
Medication
Acquired megacolon - Idiopathic megacolon, toxic megacolon, megacolon secondary to infection (c.diff or chagas), Pheochromocytoma, and other neurologic, systemic and metabolic diseases
What is aganglionic megacolon also known as?
Hirschsprungs disease
What is Hirschsprung’s disease?
a congenital disorder of the colon in which parasympathetic ganglion cells in the walls of the myenteric plexus are absent
The length of colon without innervation can very and this aganglionic section of colon can’t relax = becomes constricted = loss of movement of faeces = obstruction in the bowel and proximal to this obstructed the bowel becomes distended and full
What causes Chagas’ disease?
Trypanosoma cruzi, a flagellate protozoan transmitted by the feces of a hematophagous insect, the assassin bug, when it feeds
Can also be acquired congenitally through blood transfusion/transplantation or even contaminated food
What proportion of the population over 65 experience a degree of incontinence?
7%
What is minor faecal incontinence?
Inability to control flatus or liquid stool causing soiling
What is major faecal incontinence?
Frequent and inadvertent evacuation of stool of normal consistency
What proportion of primiparous women experience a degree of faecal incontinence?
Up to 30%
What are the main causes of faecal incontinence?
Congenital
Anal sphincter dysfunction - structural damage, pudendal nerve damage or perineal descent
Rectal prolapse
Faecal impaction with overflow diarrhoea
Severe diarrhoea - UC, functional diarrhoea, IBS
Neurological and psychological disorders
What can cause anal sphincter structural damage?
Surgery
Vaginal hysterectomy
Obstetric injury during childbirth
Trauma
Radiation
Perianal crohns disease
What can cause pudendal nerve damage leading to anal sphincter dysfunction?
Childbirth
What can cause perineal descent?
Straining
What neurological and psychological disorders can lead to faecal incontinence?
- Spinal trauma (S2–S4)
– Spina bifida
– Stroke
– Multiple sclerosis
– Diabetes mellitus (with autonomic involvement)
– Dementia
– Psychological illness
How is anal sphincter damage assessed?
Endoanal ultrasonography or pelvic MRI
How is faecal incontinence managed?
Bowel habit regulation
Sacral spinal nerve stimulation
Surgery for anal sphincter trauma
What drugs can alter sphincter tone?
Nitrates
Calcium channel antagonists
Beta blockers
Sildenafil
SSRI
Cocaine
Benzos
What drugs can cause loose stools?
Laxatives
Metformin
Orlistat
SSRI
Antibiotics
PPIs
Antacids that have magnesium in
Chemotherapy drugs
NSAIDs
What drugs can cause constipation?
Magnesium-containing antacids
Digoxin
Loperamide
Opioids
TCA
Aluminium or calcium-containing antacids
Codeine/opiates
NSAIDs
Antihistamines
Iron supplements
What foods can exacerbate faecal incontinence?
Fibre
Fruit - rhubarb, figs, prunes, plums
Veg - beans, pulses, cabbage, sprouts
Spices
Artificial sweeteners
Alcohol
Lactose
Caffeine
Excessive vitamin and mineral supplements
Olestra fat substitute
What are the 2 medical causes of faecal incontinence that require an emergency referral?
Cauda equina syndrome
Acute stroke
How should you manage a person with faecal incontinence?
Review and modify drugs
Serology testing for coeliac disease
Manage cause of diarrhoea if found e.g. IBD, gastroenteritis, pelvic floor dysfunction
Advise to stop smoking
Pelvic floor muscle training, bowel retraining, specialist dietary assessment and management, biofeedback, electrical stimulation, rectal irrigation
Surgery
Psychoglocial and emotional support
Change diet
Bowel habit - empty bowel after meal, adopt sitting.squatting position and dont strain
Toilet access
Antidiarrhoeal medication - loperamide
Continence products
Coping strategies
Why is loperamide the drug of choice for faecal incontinence?
Reduces diarrhoea and increases internal anal sphincter tone
What are acute causes of diarrhoea?
Gastroenteritis
Diverticulitis
Antibiotic therapy
C.diff
Constipation causing overflow
Appendicitis
What are some chronic causes of diarrhoea?
IBS
IBD
Colorectal cancer
Coeliac disease
Thyrotoxicosis
Laxative abuse
What is melanosis coli?
a disorder of pigmentation of the bowel wall
What is seen on histology in melanosis coli?
Pigment-laden macrophages
What is melanosis coli associated with?
It is associated with laxative abuse, especially anthraquinone compounds such as senna
