Transcript Slide 1

Bugs in the BellySome are good, some are
bad
Mark H. Mellow, MD
INTEGRIS Digestive Health Center
405-713-4430
Normal gut bacteria are FRIENDLY
- They not only don’t cause
disease, they prevent and fight off
disease
We know very little about our
friendly bacteria
 We have always relied on culturing
techniques to identify bacteria
 Over 80% of friendly bacteria cannot be
cultured. New “hi-tech” method- DNA
sequencing
Expect an explosion of info on gut
bacteria in the next 20 years
Bug Facts
We have 10-1000 x as many bacterial cells in
our bodies than we have our own cells
The Gastrointestinal tract has most of
our bacteria- 10-100 trillion bacteria
1,000,000,000,000
Role of normal Bacteria in Disease
Prevention
(colonization resistance)
1. Produce anti-microbial factors
2. Compete for binding sites on epithelial surface
3. Utilize nutrients more efficiently
4. Interact with intestinal lymphocytes to modulate
immune response
Genes and diet are the 2 major
determinations of type and
function of our gut bacteria but gut
bacteria are altered by use of
antibiotics, sometimes for months!
Probiotics
 Live microorganisms which, when consumed
in adequate amounts, confer a health benefit
“Good Bacteria”
Probiotics Basic Requirements to be
Effective
1.
Must be live bacteria
2.
Must survive acid and bile digestion
Most Probiotics in 2009 are of only 2 major
types- Lactobacillus and Bifido bacteriaYogurt
Several others may be as good or better
C Diff
The Organism
Gram + bacillus
Anaerobic
Spore forming
Intestinal flora
(up to 35% hospitalized patients, 3% of healthy
adults)
Leading cause of
Antibiotic associated
Diarrhea and colitis
CDiff Pathogenicity
Toxins are key- A and/or B. Non pathogenic
strains don’t produce toxins.
Mode of Transmission
 Fecal-oral route
 Poor hand hygiene practices
 Poor infection control practices
(use of contaminated equipment between patients)
 Spore dormancy
Diagnosis of CDI
 Stool for C Diff toxin A&B
EIA: Rapid, cheap, not very sensitive
PCR: Rapid, moderate price, very sensitive
Endoscopy
• Pseudomembranous
Colitis
Raised white/yellow
nodules with skip
areas of inflamed
mucosa
Key factors in contracting
C Diff
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Age over 65
Antibiotic use, esp. Fluoroquinolones
Being in the hospital
Chemotherapy
Colorectal Surgery
Proton Pump Inhibitors
Renal failure
HAND HYGIENE
C Diff
 More Common
Four Fold increase since 2001 in US
500,000 US cases; 15,000 deaths
Law of Unintended Consequences
 CMMS mandate for early use of antibiotics in
suspected pneumonia
 Strong correlation in antibiotic use 2002-2008
and C Diff rates
C Diff
 More Virulent
New strain NAP1/027- makes
10-30 times more toxin
War on C Diff committee
 Dr. Ramgopal
 Dr. Brown
 Dr. Mellow
 Dr. Rankin
 Dr. Stokesberry
 Dr. Muchmore
 Gwen Harrington, RN
War on C Diff
 Prevention
 Early Detection
 Better Treatment
C Diff Prevention
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Isolation
Gowns
Gloves
Handwashing-Chlorhexidine in all rooms
BP cuffs, and stethoscopes in each room
Room equipment sterilization
Dr. recommendations: Trashcan near door, for gown, etc
disposal
Sink area uncluttered, large gloves.
Nurse recommendations: Doctors need to follow
precautions also!
Distribution of Clostridium Difficile isolates
taken the room environments of three patients
in an oncology unit
Patient with C. diff
colitis and diarrhea
Total sites
cultured (+)
19/97 (19.6)
No. positive/no. sampled (%)
Asymptomatic stool
carrier of C diff
5/74 (6.8)
Patient with diarrhea
culture neg for C diff
2/78 (2.6)
Early recognition=
Earlier isolation,
earlier onset of treatment
Early Recognition
Allow nurses to collect stool specimen for new
onset diarrhea
Stools are batched to lab in mid morning, so collect
evening or early a.m. specimen
Write Dr._______, phone order-Doctor will sign in
a.m.
War on C Diff Results
 4/08-3/09 C Diff 11.3 for 1000 admissions
(national average 13 per 1000)
 4/09-3/10 C Diff 6.9 per 1000 admissions
40% decrease
Study: Prevention of C Diff with
Probiotics
BMJ: Yogurt preparation (activia)
Randomized control trial
9 of 53 C Diff with placebo
0 of 57 C Diff with yogurt
No USA trials
Lots of exclusions
Efficacy of Probiotics in C Diff Prevention
(am J. Gastro 2/10)
• Hospitalized patients ages 50-70, newly
started on antibiotics
• Randomized to placebo, 50 billion cfu or 100
billion cfu capsules (50 billion cfu/capsule)
Biok
AAD: 44% with placebo 28% with 50 billion;
15% with 100 billion
CDI: 23% with placebo 9% with 50 billion; 1%
with 100 billion
Co-Prescribe Probiotics
with Antibiotics
Write: Give Probiotics
Treatment of Initial Episode of CDI
 Average risk and average severity of CDI:
Metronidazole
 Patients condition not improving: Vancomycin
 High risk patient or severe CDI (WBC,
Creatinine, Albumin): Vancomycin
 Ileus: Intra colonic Vancomycin, IV
metronidazole, surgical consultation
Intra colonic and/or fecal Vancomycin
levels are arithmetically related to oral
dose
Oral Vanco Dose Relates to Colonic
Vanco Levels
125mg Q6=350mg/L stool
250mg Q6=447mg/L
500mg Q6=714mg/L
The Problem of Recurrent CDI
 25 % of patients with CDI will experience a
recurrence
 50% of patients with recurrence will have
multiple recurrences
 Standard therapy often ineffective. Need
innovative treatments
Clinical Predictors of Recurrence of
CDI
 Age >65
 Severity of index infection
 Antibiotic use after CDI treatment
 Use of Acid Suppressants
 Inadequate patient’s immune response
Nitazoxanide
(Alinia)
 Approved for treatment of Giardia and
Cryptospordia
 As effective as Metronidazole and Vanco for
initial cure
 50% cure rate in patients who failed
Metronidazole
Fidaxomicin
 Oral agent vs. C Diff
 Inhibits an enzyme (RNA polymerase) that
results in death of organism
 As good as Vancomycin in treatment
 Significantly lower recurrence rate
 Narrower spectrum of action-kills fewer “non
C Diff” anaerobes
 Cost
Fidaxomicin vs. Vancomycin for
CDI
NEJM 2/2011
RCT: over 600 patients
Cure rate of V=F ~90% (slightly less in severe disease)
Recurrence rate F better than V: 25%vs. 15%
But equal recurrence rate in patients with aggressive
strain and patients with prior CDI.
Humanized antibiodies to CDT
A and B
 Prevent recurrence
Placebo controlled
Company sponsored
Worked best in less sick patients
Did he say Fecal Transplant??
YES
What is Fecal Transplant?
 Obtaining fecal matter from a healthy person
and placing it in the intestine of another person
Why would Fecal transfer work?
 Antibiotics knock out many “good” bacteria
that prevent C Diff proliferation
 Normal person’s stool has these “good”
bacteria
Role of normal Bacteria in Disease
Prevention
(colonization resistance)
1. Produce anti-microbial factors
2. Compete for binding sites on epithelial surface
3. Utilize nutrients more efficently
DECREASED MICROBIAL
Diversity in RCDI
 Small study
 Genomic analysis of types of bacteria in stool:
Controls
1st attack of CDI
Recurrent CDI
Many fewer species in RCDI and in 1 patient with 1st
attack- developed recurrence 10 days later!
Bacteria with colonizing resistance factors missing in
RCDI
Fecal Transplant Donor
Exclusions
 Antibiotics
 Recent or chronic diarrhea
 Immune suppression
 Chemotherapy
 Prior CDI
Fecal Transfer Testing
Donor blood: Hepatitis A,B,C;HIV;Syphlis
Stool: CDiff, C&S, O&P
$375.10
Recipient blood: Hepatitis A,B,C;HIV;Syphlis
$275.00
(negotiated “Private Pay-discounted” by DLO)
FT Process
 D/C CDI treatment 48 hours pre procedure
 Colon prep for patient
 Mild laxative for donor
 Stool mixed with non bacteriostatic saline
 400-600 cc placed in colon
 Imodium 4mg
INTEGRIS Baptist Medical Center
Experience
Fecal Bacteriotherapy
20 Patients treated
Average # recurrences- 4
Average time of disease- 11.5 months
18 of 20: Resolution of diarrhea within 10 days
1 retreated with different donor = cure
1 recurrence at 7 months
“Double Transplant”
 37 year old male with cirrhosis developed
CDI. Flagyl, Vancomycin, sarchromyses
failed
 Fecal Transplant successful
 Subsequent Liver Transplant!
Questions?