5. Course in the Wards
Gastroenteritis with Dehydration
IV fluids
IV Rocephine shifted to Augmentin
AKI and Hypernatremia
Deconditioning
6. Course in the Wards
Gastroenteritis likely antibiotic related
Cd toxin not detected
Antibiotics discontinued
Diarrhea resolved
Delirium likely stroke disease
Poor Oral intake
Depression – fluoxetine, mirtazipine
Worsening Dementia
NGT was inserted
7. Course in the Wards
Refeeding syndrome
Low magnesium (0.57 )
Low phosphate (0. 38)
Low potassium ( 3.3)
Pneumonia
Iv tazocin
8. Course in the Wards
Recurrence of diarrhea
CD toxin : Negative
CD PCR : Positive
Metronidazole 500 mg per NGT 6 hourly
Vancomycin 250mg per NGT q6hourly
16. Clostridium difficile
Pathonegesis
FROM THE FOLLOWING ARTICLE:
Clostridium difficile infection: new developments in epidemiology and pathogenesis
Maja Rupnik, Mark H. Wilcox & Dale N. Gerding
Nature Reviews Microbiology 7, 526-536 (July 2009)
17. Risk factors
Antibiotics
Hospitalization
Advanced age
Severe illness
Gastric acid suppression
Enteral feeding
Gastroentrointestinal conditions & procedures
Obesity
Cancer chemotheray
Hematopoetic transplantation
Antidepressant
18. Antimicrobial agents that may
induce Clostridium difficile
diarrhea and colitis
Frequently
associated
Occasionally
associated
Rarely
associated
Fluoquinolones Macrolides Aminoglycosides
Clindamycin Trimethoprim Tetracyclines
Penicillins sulfonamides Chloramphenicol
Cephalosphorins Metonidazole
Vancomycin
19. Clinical Manifestations and
Diagnosis
Carrier
state
Diarrhea
and colitis
Pseudomem
branous
colitis
Recurrent
disease :
relapse vs
reinfection
Fulminant
colitis
20. Clinical Manifestations
96% of patients with symptoms had
received antimicrobials with 14 days
before the onset of diarrhea
Symptoms begin soon after colonization
( median time onset 2-3 days )
Fever, cramping, abdominal discomfort
and peripheral leukocytosis are common
Arthritis, bacteremia
Unexplained Leukocytosis
21. Diagnosis
Presence of moderate to severe diarrhea or
ileus
And either
A stool positive for C. Difficile toxins or
toxigeneic c. Dificile
Endoscopic or histologic findings of
pseudomembranous colitis
22. Diagnostics Tests
Only stools from patient with diarrhea should be tested for
CD
• ( strong recommendation, High Quality evidence )
NAAT ( PCR are superior to toxins A & B EIA testing as a
standard diagnostic test for CDI
• (strong recommedation, moderate quality evidence )
Glutamate Dehydrogenase can be used in 2 to 3 step
screening algorithms with subsequent toxin A and B EIA
testing, but the sensitivity of such is lower than NAATS
• ( strong recommendation, moderate quality evidence )
Guidelines for diagnosis, treatment, and Prevention of clostridium difficle infections
American College of Gastroenterology
Published online 26 feb 2013
2010 UPDATE BY Society for Healthcare Epidemiology of America and infectious
diseases Society of America
23. Diagnostic testing
Repeat testing should be discourage
• Strong recommendation, moderate quality evidence
Testing for cure should not be done
• ( strong recommendation, moderate quality evidence )
Stool culture is most sensitive and essential in
epidemiologic studies
• ( good evidence to support recommendation)
Guidelines for diagnosis, treatment, and Prevention of clostridium difficle infections
American College of Gastroenterology
Published online 26 feb 2013
2010 UPDATE BY Society for Healthcare Epidemiology of America and infectious diseases Society of America
24. Other Methodologies
Sigmoidoscopy or colonoscopy
• Detects pseudomembranous colitis in 51-55% of
CDI cases
Histopathology
Abdominal CT SCAN – facilitate diagnosis,
but not sensitive nor specific
Guidelines for diagnosis, treatment, and Prevention of clostridium difficle infections
American College of Gastroenterology
Published online 26 feb 2013
2010 UPDATE BY Society for Healthcare Epidemiology of America and infectious diseases Society of America
25.
26.
27.
28. CDI Severity Scoring System
Severity criteria
Mild to moderate Diarrhea + s/s not meeting severe or
complicated criteria
Severe Disease <3g/dl + 1 of the ff:
WBC >15,000 cells/mm3, abdominal
tenderness
Severe and
Complicated disease
Any of the following attributable to CDI
Admission to ICU
Hypotension +/- vasopressors
Fever >38.5 C
Ileus or significant abdominal distention
Mental status changes
WBC >35,0000or <2,000
Recurrent CDI Recurrent within 8 weeks of completion of
therapy
29. Factors to Consider Before
Treating
AGE
Peak
White cell
count
Peak
serum
creatinine
30. Treatment
• Metronidazole 500mg TDS or 250mg QDS for 10-14
days THEN
• Vancomycin 125mg orally QDS 10-14 days. If no
response
Mild
disease
• Vancomycin500mg 4x/day + metronidazole 500mg every
8 hours IV
• If complete ileus : add rectal vancomycin
Severe
disease
• If symptoms is mild, conservative management may be
appropriate
• If antibiotics are needed, repeat treatment as in initial
episode
• Alternative : Fidaxomicin 200mg BD x 10 days
First
Relapse
UPTODATE
31. Treatment
• Tapering and pulsed vancomycin
with or without probiotics
• 125mg QDS for 7-14 days
• 125 BD x 7 days
• 125 once x 7 days
• 125mg orally every other day for 7
days
• 125mg orally every 3 days x 14 days
• Alternative : Fidaxomicin 200mg
orally BD x 10days
Second
Relapse
UPTODATE
32. Treatment
• Fidaxomicin 200mg
Orally BD x 10 days
• Alternative :
vancomycin 125mg
QDS x 14 days
followed by rifiximim
400mg BD x 14 days
Subsequent
relapse
33. Fidaxomicin
Macrolide, bactericidal
Narrower antimicrobial spectrum than
Metronidazole & Vancomycin
3RCT : in non severe C. Difficile , clinical
cure rates with vacomycin were similar
Recurrence is less often among patients
with non NAP1 strain ( 10 vs 28 % )
UPTODATE
34. Probiotics
May be effective for prevention and
treatment
Alteration of intestinal flora
Antimicrobrial activity
Intestinal barrier protection
immunomodulation
Administration consist only of regimens
with demonstrated efficacy
Dosage of >10 billion CFU per day
A cocrane review: insufficient evidence to
recommend as adjunct in treatment
UPTODATE
35. RICE WATER
Rice water and diarrhoea
The advantage of using rice water is that rice is cooked
daily in South East Asia.
WHO photograph by Dr Gramiccia In South East Asia, rice is
prepared in two ways - to produce either dry, cooked rice or,
with extra water, rice porridge. This leaves a fluid (rice water)
on top of the cooked rice grains.
Professor Wong Hock Boon, a paediatrician working in
Singapore, has been using rice water to rehydrate babies for
several years. If the babies are bottle-fed rice water is given
exclusively for the first 24 hours of treatment - breastfeeding
can continue as normal (1).
Professor Wong and his colleagues have found that many
babies who have not responded to other rehydration solutions
respond well to rice water. If diarrhoea starts again with the
re-introduction of milk, extra rice water is given with additional
rice porridge. Older babies are sometimes given rice porridge
alone.
36. Treatment
Antimotility Agents and Opoids
Associated with increase risk of toxic
megacolon
IVIG
No effective immunotherapy is currently
available
Does not have a role as sole therapy for
RCDI
May be helpful in patient with
hypogammaglobulimenia
37. Colectomy
Consider in severely ill patients
Monitoring serum lactate and White cell
may be helpful in prompting a decision
to operate
38.
39. Fecal Microbiota
Transplantation
Patient selection
Severe and Recurrent C. Difficile infection
Cure rates 81-94% in patients with
recurrent disease
Response within 24h to 12 days
Only method capable of providing
durable implantation of probiotics
Route of administration :
Colonoscopy, nasogastric, enema
40. Infection Control, & Prevention
A hospital – based infection contol program
can help decrease the incidence of CDI
Routine screening for C. Difficile in
hospitalized patients without diarrhea is not
recommended and asymptomatic carriers
should not be treated
Antibiotic stewardship is recommended to
reduce the risk of CDI
41. Infection Control and
Prevention
Gloves and gowns upon entry to a room
Emphasize compliance with practice of
hand hygiene
Hand wash with soap and water after
caring for or contacting patient with CDI
Accommodate patients with CDI in
private room with contact precaution
42. Environmental Cleaning and
Disinfection
Identification and removal of environmental
sources of C. Dificille including
replacement of electronic rectal thermometers
with disposable, can reduce the incidence of CDI
Use chlorine-containing cleaning agents or
other sporicidal agents
to address environmental contamination in area
associated with increased rates CDI
43. Prognosis
Mild disease, may recover without
specific therapy
Debilitating and can last for several
weeks
20-27% treated for first episode ,
relapse after successful completing the
antibiotics , 3days -3week after
treatment
65%- relapse rate with patient with 2 or
more relapses
44. Prognosis
Adverse outcomes
Treatment failure
Severe or complicated infection
Sepsis
Need for admission to ICU
Need for colectomy
Increase length of hospital stay
Need for hospitalization for community acquired
CDI
Mortality 4.2-6.9%
45.
46.
47.
48. Sources
UPTODATE
American College of Gastroenterology
2010 Update by Society for Healthcare
Epidemiology of America (SHEA ) and the
Infectious Diseases Society of America
Center for Infectious Disease
CGH Guidelines
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2224300/figure/f1/
https://www.nuh.nhs.uk/media/1069241/new_cdiff_testing_and_reporting.pd
f
49. Proposed algorithm for detection of C. difficile in fecal specimens submitted for C. difficile testing. Tests used are C.DIFF
CHEK-60 for C. difficile specific antigen (glutamate dehydrogenase) and TOX A/B QUIK CHEK for toxin A/B (both
TechLab/Wampole). The percentage values refer to the total numbers of stool specimens analyzed (n = 1,468). Results for
nine specimens (0.6%) which did not fit into the described categories are not included. J Clin Microbiol. Jan 2008; 46(1):
328–330
52. Prevention strategies
Early detection and isolation
Rapid implementation of contact precautions
Vigilant screening for new onset diarrhea in
patients at risk and rapid and accurate
testing
Contact precaution
53. Prevention and strategies
Hand Hygiene
Healthcare personel should hand wash
hands with soap and water
Alcohol based hand rub does NOT eradicate
C. Difficile spores
Adherance to gloves is also important
56. Factors contributing to the development of Clostridium difficile colonization and
diarrhea [adapted, with permission, from Johnson S, Gerding DN. Clostridium difficile-associated
diarrhea. Clin Infect Dis 1998;26:1027-36, published by the University of Chicago Press, Infectious
Diseases Society of America; 1998]. Photo: Lianne Friesen and Nicholas Woolridge
57. How C. Difficile Spreads
L.S.W . 96/female, went to doctor, diagnosed with Pneumonia, given antibiotics that put
her at risk of developing antibiotic related diarrhea
1 ½ month later : admitted to Pneumonia, given another course of antibiotics. A health
care worker forgetting to wash hands /wear gloves after attending to a C. D. Infected
patient next to her bed, infecting patient
At Rehab facility – with no strict contact precaution. L.S.W. developed diarrhea, CD toxin
was not tested at that time. health care worker attends to her, infects another patient
Few days later, persistence of diarrhea, retested for CD, which turns out to be positive.
Was given proper antiobitiotics, with resolution of diarrhea
58. Recurrent Disease
Complete abatement of CDI symptoms
while on appropriate treatment
Followed by subsequent reappearance
of diarrhea and other symptoms after
treatment has been stopped
Risks factors : > 65 years old, severe
underlying medical condition, need
forongoing therapy with concomitant
antiobiotics during treatment with CDI
Pathophysiology :not fully understood
59. FIGURE 1 | Treatment algorithm for recurrent Clostridium
difficile infection
FROM THE FOLLOWING ARTICLE:
Treatment of refractory and recurrent Clostridium difficile infection
Christina M. Surawicz & Jacob Alexander
Nature Reviews Gastroenterology & Hepatology 8, 330-339 (June 2011)
Hinweis der Redaktion
Places a high burden to our health care system
A leading cause of hospital associated GI illness
Forms heat resistant spores that can persist in the environment for several months to years.
It is difficult to treat, it can be debilitating
Ill briefly discuss a case
And ill present a the guidelines in the management , prevention and control
Presented with fever after last discharge in March 2014, associated with lethragy and poor appetite
5 days prior to admission , she had episodes of watery stools 2 x perday
Trial of antidepressant given
The orange represent normal bacterial flora
In green, represent c.d
Ist scenario
2nd scenario – nil c.dif
Ist person has clostridium dificle, small percentage of adult
Given antibitocs for some reason
But wipes out normal flora, doesnt
Nil competing bacteria, hence it ploloferates
It cause diarrhea secretes toxins
90 0ercent has normalflora
Given antibiotics for somme reason
Ythe antibiotics clears out normal flora
in nursing home,
A health care worker, doesnt clean hands
Tocuh patient
Infecting
No competing bacteria
clostridium overgorws
More common in elderly
Increase in overall incidence
Transmission :
person to person contact
Fecal oral route
Principally occuring within inpatient facility
Healthy people usually dont get infection, because they have millions of bacteria to fight for CD
shed on
That the fact that they produce spores is very critical. Because its very difficult to eradicate eradicate. Alcohol rubs dont work.
Over the years.....a virulent has been arising
Patients are exposed to C. difficile spores through contact with the hospital environment or health care workers. After taking an antibiotic, they develop CDI if they acquire a toxigenic C. difficile strain and fail to mount an anamnestic serum immunoglobulin G (IgG) antibody response to toxin A (ToxA; also known as TcdA)64; if they can mount an antibody response they become asymptomatically colonized with C. difficile. If they acquire a non-toxigenic C. difficile strain, they also become asymptomatically colonized. Colonized patients have been shown to be protected from CDI126.
Patients are resistant to CDI if their normal gut flora is not disrupted by antibiotics (a). Once antibiotic treatment starts, infection with a C. difficile strain that is resistant to the antibiotic is more likely while the antibiotic is being administered owing to the presence of the antibiotic in the gut (b). When the antibiotic treatment stops, the levels of the antibiotic in the gut diminish rapidly, but the microflora remains disturbed for a variable period of time (indicated by the break in the graph), depending on the antibiotic given (c). During this time, patients can be infected with either resistant or susceptible C. difficile. Finally, after the microflora recovers, colonization resistance to C. difficile is restored (d).
C. difficile colonizes the intestine (colon) after disruption of the normal intestinal flora. To what extent adhesion and biofilm production are involved in the pathogenesis of C. difficile is unknown; in the schematic, bacterial cells are shown as free cells and attached to host cells. Toxigenic strains produce toxin A and toxin B (TcdA and TcdB). TcdA binds to the apical side of the cell and, after internalization, causes cytoskeletal changes that result in disruption of tight junctions and loosening of the epithelial barrier, in cell death or in the production of inflammatory mediators that attract neutrophils. Disruption of tight junctions enables both TcdA and TcdB to cross the epithelium. TcdB binds preferentially to the basolateral cell membrane. Both toxins are cytotoxic and induce the release of various immunomodulatory mediators from epithelial cells, phagocytes and mast cells, resulting in inflammation and the accumulation of neutrophils. In an animal model, TcdB was shown to have a tropism for cardiac tissue, which would require that TcdB enter the bloodstream.
A history of treatment with antibiotics or antineoplastic within the previous 8 weeks is present in majority of cases. Antibiotic use, especially a type of antibiotic that is broad-spectrum (is able to treat a wide variety of bacteria) or if you have been taking antibiotics for an extended period of time
Hospitalization
Advanced age
Living in a nursing home or extended-care facility
Colon problems, such as inflammatory bowel syndrome or colorectal cancer
Weakened immune system
Previous C. diff. infection
Being 65 years of age or older
Surgery of the gastrointestinal (GI) tract
Abdominal surgery that requires moving the intestines aside
2 related studies documented an incresed risk of CDI in adults taking antidepressant mirtazipine and fluoxetine
Among cephalosporins : the 2nd and third gens have increased risk
A brief exposure to any single antibiotic can cause C. Difficile colitis. Aprolonged antibiotics course or the use of 2 or more antibiotics increased the risk of disease.
Vancomycin and metronidazole have been shown to cause disease
water diarrhea – cardinal symptom of CDI
The clinical mnaifestations of infection with toxin producing strains of c. Difficele range from
Asymptomatic carrier state to fulminant disease with toxic megacolon.
Several studies have showned that 50 % of hospital patients colonize C. Dificile are symptomless carries, possibly reflecting the natural immunity.
The presence of diarrhea is defined as passage of 3 or more unformed stools in 24 or fewer consecutive hours.
Same criteria is use to diagnose recurrent CDI.
Whta are the best testing stragegies to diagnose CDI in the clinical laboratory and what are the acceptable options?
PCr is an excellent confirmatory test
Data on LAMP testing is not yet sufficient to recommend it
Few published data on the performance of one of the 3 and 4,
Metaanalysis of three PCR assays, indicate that they have similar sensitivities of the a specificities of 90% and 95%, rspectively
Stool leukocytes, none specific
Pseudomembaranous colitis can only be diagnosed by direct visualization of pseudomembranes on lower Gastrointestinal endoscopy or by histopathology
Three factors may indicate a severe or complicate course and should be considered when initiating a therapy.
The influence of greater age probably reflects a senecnese of the immune response against C. Dificile and its toxins the greater age has been consistently related to adverse outcomes.
Leukocytosis likely reflects the severity of colonic inflammation, complications are more common in patients with leukocytosis of 15,000 or higher. The course of disease is sometimes catastrophic in patients with leukocytosis of > 50,000 or higher
An elevated creatinine may indicate severe diarrhea with subsequent dehydration or inadequate renal perfusion.
Consider in severely ill patients
Monitoring serum lactate and White cell may be helpful in propting a decision to operate
lactate
Lactate of 5mmol/Land wcc of 50,000 have been associated with greatly increased perioperative mortality. If surgical managemnt is necessary, perform subtotal colectomy with preservation of rectum
Antibiotics are the bigger risk factors for CDI, numerous studies have shown that restriction of the most common offending antimicrobials is effective in CDI prevention.
Minimizing the frequency and duration of antimicrobial therapy and the number of antimicrobial agents prescribes to reduce CDI
Measures for Health Care Workers, Visitors, Patient
30 % of hospitalized patients who have antibiotic associated diarrhea will have CDI