Transcript Clostridium difficile: the new hospital plague?

CLOSTRIDIUM
DIFFICILE:
THE NEW HOSPITAL
PLAGUE?
WHY IS CONTROL OF THIS
DIARRHEA-CAUSING DISEASE
MORE IMPORTANT NOW THAN EVER ?
John L. Dyson RN, BSN
MSN 621
Alverno College, Milwaukee, Wisconsin
Last updated May 12, 2006
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1. PATHOPHYSIOLOGY OF C-DIFF
2..DISCOVERY OF C-DIFF.
3. GENETICS AND C-DIFF.
4. TREATMENT OF C-DIFF.
5. WHO IS AT RISK FOR COMPLICATIONS?
6. SYMPTOMS OF C-DIFF.
7. “THE ADVERSE EFFECTS OF CONTACT
ISOLATION AND LONELINESS ON PATIENTS
8. REFERENCES
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HOW IS C-DIFFICILE SPREAD?
(CLICK on YOUR ANSWER BELOW to CHOOSE)
BY AN INHALED BACTERIUM?
BY AN AIRBORNE VIRUS?
BY THE FECAL/ORAL ROUTE?
(sounds: Microsoft Office 2003)
NO….
NOT AN INHALED
BACTERIUM!
…try again!!
(click HERE to try again)
NO…
…IT’S NOT A VIRUS
…try again!!
(click HERE to try again)
YES!!!
…C-DIFFICILE IS A BACTERIUM
IN THE FORM OF A SPORE!
• It is transmitted by the fecal-oral
route when shed in feces & released.
• It can live up to 70 days in the
environment!!
Medical College of Wisconsin (2000)
http://www.healthlink.mcw.edu/article/954992292.html)
Pathophysiology of C-difficile
Sunenshine & McDonald (2006)
www.cdc.gov/ncidod/dhqp/pdf/infDis/Cdiff_CCJM02_06.pdf
(picture used with permission)
Sunenshine & McDonald (2006)
www.cdc.gov/ncidod/dhqp/pdf/infDis/Cdiff_CCJM02_06.pdf
(Picture used with permission)
Pathophysiology of C-Difficile
Sunenshine & McDonald (2006)
www.cdc.gov/ncidod/dhqp/pdf/infDis/Cdiff_CCJM02_06.pdf
(picture used with permission)
The Onset of
Pseudomembraneous Colitis
TWO STEPS OCCUR:
1. Normal Flora must
be disrupted (occurs
with antibiotics).
2. Clostridium difficile
must be ingested.
(These do not have to
occur in this order)
Sunenshine & McDonald (2006)
www.cdc.gov/ncidod/dhqp/pdf/infDis/Cdiff_CCJM02_06.pdf
(picture used with permission)
“SOME PATIENTS
DEVELOP C-DIFF,
WHILE OTHERS DO
NOT…”
“IT IS UNCLEAR
WHY” THIS IS SO…
Sunenshine & McDonald (2006)
www.cdc.gov/ncidod/dhqp/pdf/infDis/Cdiff_CCJM02_06.pdf
(picture used with permission)
ACTUAL ENDOSCOPY PICTURES:
picture courtesy of Carol
Hein, RN, MSN (used
with permission)
NO LONGER THE DISEASE OF
THE ELDERLY
AFFECTS:
• ACUTE CARE PATIENTS
• PEDIATRIC PATIENTS
• TUBE-FED PATIENTS
• HEALTHCARE WORKERS
• FAMILIES
WHICH OF THESE PRODUCES
THE DIARRHEA SYMPTOMS OF
C-DIFF?
TOXINS “TD-1” AND “TD-2”
TOXINS “A” AND “B”
TOXINS “C” AND “DIFF”
NO !
TRY ANSWERING AGAIN!
YES…
YOU GOT IT !!
Sunenshine & McDonald (2006)
(picture used with permission)
HISTORY OF C-DIFF
• FIRST ISOLATED IN THE 1930’S
• NAMED “CLOSTRIDIUM DIFFICILE” DUE TO
DIFFICULTY ISOLATING THE BACTERIUM SPORE.
• SPORE CARRIES “TOXIN A” AND “TOXIN B”.
• RESULTS IN “PSEUDOMEMBRENOUS COLITIS”WHICH PRESENTS WITH THE DIARRHEA SEEN
Conly (2001)
WHEN IT WAS FIRST LINKED
TO DISEASE IN 1978…
THE C-DIFF BACTERIA WAS FOUND TO
BE:
• SPORE-FORMING
• ANAEROBIC (REQUIRES NO OXYGEN
TO SURVIVE)
Sunenshine& McDonald (2006)
www.cdc.gov/ncidod/dhqp/pdf/infDis/Cdiff_CCJM02_06.pdf
• THERE ARE MORE THAN 3 MILLION
C-DIFF CASES ANNUALLY IN THE U.S.
• C-DIFF IS SEEN FOLLOWING
LONGER- TERM ANTIBIOTIC
THERAPY
• THE DISEASE DESTROYS INTESTINAL
MUCOSA, INFLAMING THE LARGE
INTESTINE
• THE RESULT: MUCOSY
DIARRHEA
Pothoulakis (2001)
http://www.aboutibs.org/Publications/CDifficile.html.
(picture: www.the-collective.net/~punxi/old/mompics,
used with permission)
SYMPTOMS:
• MILD CASES: FREQUENT, FOUL
SMELLING, WATERY STOOLS
• MODERATE CASES: BLOODY, MUCOUSY
DIARRHEA, ABDOMINAL CRAMPING- AND
POSSIBLY AN ABNORMAL HEART RHYTHM (DUE
TO AN ELECTROLYTE IMBALANCE)
Sunenshine & McDonald (2006)
www.cdc.gov/ncidod/dhqp/pdf/infDis/Cdiff_CCJM02_06.pdf
(picture, used with permission: www.cheshire-med.com/services/bugs/ecoli.html)
THE RESULT:
•
SEVERE CASES:
PSEUDOMEMBRANEOUS COLITIS,
LEADING TO:
TOXIC MEGACOLON
…AND ULTIMATELY,
. . . . DEATH!!!
FULMINANT COLITIS
• MOST SERIOUS COMPLICATION
• OCCURS IN 3% OF PATIENTS
• SEE: SEVERE LOWER ABDOMEN PAIN, DIARRHEA, HIGH
FEVER WITH CHILLS, & RAPID HEART RATE
• THIS OCCURS MOSTLY
IN DEBILITATED,
ELDERLY PATIENTS
Pothoulakis (2001)
http://www.aboutibs.org/Publications/CDifficile.html
(picture: Microsoft Office 2003)
PATIENT PRESENTATION
•
USUALLY HAVE HAD ANTIBIOTICS OR
ANTINEOPLASTICS IN PAST 2 MONTHS
• SOME COMMON ANTIBIOTICS THAT
CONTRIBUTE TO C-DIFF INCLUDE:
1. AMPICILLIN
2. AMOXACILLIN
3. CEPHALOSPORINS
4. CLINDAMYCIN
Pothoulakis (2001)
http://www.aboutibs.org/Publications/CDifficile.html
(picture: Microsoft Office 2003)
TOP 4 CAUSES OF
CROSS-CONTAMINATION
# 4. TOILETS
# 3. TELEPHONES
# 2. STETHOSCOPES
picture: http://funtavern.com/pictures/gp-germs.jpg
(used with permission)
THE NUMBER ONE REASON:
(click the picture)
(picture: Microsoft Office 2003)
CAREGIVER HANDS!!!
DID YOU KNOW….?
• C-DIFF SPORES HAVE A LIFE EXPECTANCY
OF UP TO 70 DAYS ?
• SPORES ARE RESISTANT TO DISINFECTANTS
AND STANDARD CLEANING SOLUTIONS BY
HOUSEKEEPING ?
• ALCOHOL-BASED “PUMP” SANITIZERS
DO NOT KILL THE SPORE?
Medical College of Wisconsin (2000)
http://healthlink.mcw.edu/article/954992292.html
THE RESULT…
• LONGER HOSPITALIZATIONS
• CHRONIC DIARRHEA IN SOME ELDERLY
• SERIOUS / LIFE THREATENING DISEASE
Stelfox, Bates, & Redelmeier (2003)
THE C-DIFF GENOMIC
PATHOGENOCITY
LOCUS
- Identified as “Toxin A” & “Toxin B”
(Also known as tcdA and tcdB)
- A number after the locus identifies
the mutation site (IE: tcdB1470)
Rupnik, Dupuy, et. al. (2005)
http://jmm.sgmjournals.org/cgi/content/full/54/2/113#F13
Toxin “A” & the Neurokinin-1
Receptor
STUDIES WITH LABORATORY MICE HAVE SHOWN:
1.
TOXIN “A” BINDS TO THE NEUROKININ-1 (NK-1) RECEPTOR
IN THE INTESTINAL LINING.
2.
THE FAMILY OF Rho PROTEINS (PROTEINS INVOLVED IN
CELLULAR FUNCTION) IS INACTIVATED.
3.
THE ACTIN MICROFILAMENTS (PROTEIN FILAMENTS
PROVIDING MECHANICAL SUPPORT FOR THE CELL)
BECOME DISAGGREGATED.
Castagliuolo, Riegler, Pasha, et. Al. (1998).
“Actin Microfilaments” definition obtained from: en.wikipedia.org.
(picture: Microsoft Office 2003)
A COMPLEX CASCADE EFFECT
•
•
•
Toxin “A” stimulates production of “Substance
P”, a neuropeptide affecting the Central
Nervous System and causes nausea, pain, and
can serve as a vasodilator.
Enteric (intestinal) Nerves are affected.
Macrophages (infection-fighting cells) and
Leukocytes.
Castagliuolo, Riegler, Pasha, et. al (1998)
(picture: Microsoft Office 2003)
EMBRYONIC STEM CELL
RESEARCH IN MICE SHOWS…
• REMOVING Substance “P”, causing a
deficiency of NK-1 DIMINISHED the
inflammatory changes leading to Clostridium
difficile when Toxin “A” was administered.
• This supports a direct cause-effect relationship!!
Castagliuolo, Riegler, Pasha, et. al. (1998)
(picture: Microsoft Office 2003)
TO SUMMARIZE THE
GENETICS PROCESS:
Toxin “A” binds to the Neurokinin-1 (NK-1) receptors
of the intestinal linings.
2. Rho Proteins become inactivated & Actin
Microfilaments become disaggregated, essentially
breaking down the cell.
3. Toxin “A” stimulates Substance “P”, causing nausea,
pain, & vasodilation.
4. Macrophages and Leukocytes complete the
inflammatory intestinal lining damage.
5. Toxin “A” needs Substance “P” in a causeeffect relationship, or damage is diminished.
1.
ENTER:
The NEW C-diff Strain !
NAP 1
(North American pulsed-field gel electrophoresis type 1)
FOUND IN OUTBREAKS IN NORTH AMERICA AND EUROPE!
• Produces 16x MORE Toxin “A”, 23x MORE Toxin B”, and a
third “BINARY TOXIN” (whose significance is not yet
known).
• Resistant to GATIFLOXACIN & MOXIFLOXACIN (historical
C-diff strains are not).
• POSSIBLY due to a deletion in a negative regulatory
gene.
Sunenshine & McDonald (2006)
www.cdc.gov/ncidod/dhqp/pdf/infDis/Cdiff_CCJM02_06.pdf
C-DIFF AND GENETICS:
A SUMMARY
• C-diff occurs in the clinical and natural environment.
• C-diff is a nosocomial pathogen.
• C-diff (as yet) has no specifically identified gene site.
• Genetics has helped ID the toxins to diagnose
C-Diff, but no specific genes are known to CAUSE it !
Farrow, Lyras, & Rood (2001)
http://mic.sgmjournals.org/cgi/content/abstract/147/10/2717
GLOSSARY
• TOXIC MEGACOLON: A grave
complication of ulcerative colitis resulting in
perforation of the colon, septicemia and
death.
• Click HERE to return
ANTIBIOTICS CAUSE IT…
ANTIBIOTICS TREAT IT !!
IN THE PAST IT WAS TREATED
WITH:
• INTRAVENOUS AND
ORAL METRONIZADOLE
(INEXPENSIVE)
• ORAL VANCOMYCIN (COSTLY)
Colorado Department of Public Health and Environment, (1999)
http://www.cdphe.state.co.us/hf/cdiff99.htm
(picture: Microsoft Office 2003)
The Latest Treatment
Recommended:
Sunenshine & McDonald (2006)
www.cdc.gov/ncidod/dhqp/pdf/infDis/Cdiff_CCJM02_06.pdf
(table from article used with permission)
WHEN THE DIARRHEA
GOES AWAY….
IT IS CONSIDERED
RESOLVED…
BUT…
IT CAN COME BACK!
• 12% - 24% HAVE A SECOND C-DIFF
OCCURANCE WITHIN 2 MONTHS.
• 48% - 56% ARE ACTUALLY REINFECTED
WITH A DIFFERENT STRAIN OF C-DIFF.
• PATIENTS WITH TWO OR MORE EPISODES
HAVE A 50% - 65% RISK OF RE-OCCURANCE.
Sunenshine & McDonald (2006)
www.cdc.gov/ncidod/dhqp/pdf/infDis/Cdiff_CCJM02_06.pdf
(picture: Microsoft Office 2003)
WHO IS SUSCEPTIBLE ??
EVERYONE!
THOSE MOST SUSCEPTIBLE…
ASYMPTOMATIC C-Difficile Colonization is present in:
•
Up to 3 % of healthy adults
•
As many as 50 % of infants
“The major risk factor for C. difficile
infection is antibiotic usage”
Oguz, Uysal, Dasdemir, Oskovi, & Vidinlisan (2001)
(picture: Microsoft Office 2003)
HIGHEST RISK GROUPS:
• OLDER PATIENTS
• CHRONIC RENAL
FAILURE PATIENTS
• PATIENTS WITH
NASOGASTRIC
FEEDING TUBES
• PATIENTS WITH A CDIFF HISTORY
Tal, Gurevich, et. al. (2002)
(picture: Microsoft Office 2003)
THIS IS DUE TO “PHYSIOLOGICAL
AND FUNCTIONAL CHANGES OF
THE GUT”, WHICH “ARE OFTEN
ACCOMPANIED BY AN INCREASED
INCIDENCE OF
GASTROINTESTINAL
INFECTIONS”
“ADVERSE EFFECTS OF
CONTACT ISOLATION”
PATIENTS IN ISOLATION
PATIENTS NOT IN ISOLATION
• 3.9 ROOM ENTRIES/HOUR.
• 7.9 ROOM ENTRIES/HOUR.
• 2.1 MEAN CONTACTS/HR
BY A REGISTERED NURSE.
• 4.2 MEAN CONTACTS/HR
BY A REGISTERED NURSE.
• 4.5 MINUTES OF ACTUAL
HEALTHCARE WORKER
INTERVENTION TIME PER
OCCURANCE.
• 2.8 MINUTES OF ACTUAL
HEALTHCARE WORKER
INTERVENTION TIME PER
OCCURANCE.
Kirkland & Weinstein (1999)
(picture: Microsoft Office 2003)
“HOSPITAL PATIENTS IN
ISOLATION RECEIVE INFERIOR
CARE, STUDY SAYS”
• ISOLATED PATIENTS NOT GIVEN MEALS OR
MEDICATIONS ON TIME
• CALL LIGHT RESPONSE NOT PROMPT
• HIGHER INCIDENCE OF FALLS & BEDSORES
• PATIENT/CAREGIVER BARRIERS CREATED
Bakalopoulos (2003)
http://www.thevarsity.ca.
“PSYCHOLOGICAL EFFECTS OF
SOURCE ISOLATION”
• ISOLATED PATIENTS EXPERIENCE
FREQUENT MOOD DISTURBANCES.
• CONSISTENT USE OF VERBAL & WRITTEN
INSTRUCTIONS FOR PATIENTS SEEMS TO
MINIMIZE THEIR VERBALIZED FEELINGS
OF ISOLATION FROM THE GENERAL
PUBLIC ACTIVITIES
Rees, Davies, Birchall, & Price (2000)
Sunenshine & McDonald (2006)
(picture from article used with permission)
Sunenshine & McDonald (2006)
(picture from article used with permission)
REFERENCES
Bakalopoulos, P. (2003). Hospital Patients in Isolation Receive Inferior Care, Says Study. The
Varsity-Science. Retrieved February 28, 2006 from http://www.thevarsity.ca. (“Search” title
of article; then free sign-in is required to view article.)
Castagliuolo, I., Riegler, M., Pasha, A., Nikulasson, S., Lu, B., Gerard, C., Gerard, N.P. &
Pothoulakis, C. (1998). Neurokinin-1 (NK-1) Receptor Is Required in Clostridium
difficile-induced Enteritis. Journal of Clinical Investigations, 101, 8, 1547-1550.
Colorado Department of Public Health and Environment. (1999). Management of
Clostridium difficile-Associated diarrhea: Guidelines for Long Term Care and
Rehabilitation Facilities. Retrieved February 28, 2006 from:
http://www.cdphe.state.co.us/hf/cdiff99.htm
Conly, J.M. (2000) Clostridium difficile-Associated Diarrhea - The New Scourge of the
Health Care Facility. The Canadian Journal of Infectious Diseases & Medical
Microbiology, 11, 1.
Farrow, K.A., Lyras, D. & Rood, J.I. (2001). Genomic Analysis of the Erythromycin
Resistance Element
Tn5398 From Clostridium difficile. Retrieved electronically March 1, 2006 from:
http://mic.sgmjournals.org/cgi/content/abstract/147/10/2717
REFERENCES
Kirkland, K.B. & Weinstein, J.M. (1999). Adverse Effects of Contact Isolation. Lancet, 354,
1177-1178.
Medical College of Wisconsin. (2000). Clostridium Difficile. Retrieved February 28, 2006
from: http://www.healthlink.mcw.edu/article/954992292.html)
Microsoft Office 2003. Clip Art, Animation, Sounds
Oguz, F., Uysal, G., Dasdemir, S., Oskovi, H, & Vidinlisan, S. (2001). The Role of
Clostridium difficile in Childhood Nosocomial Diarrhea. Scandinavian Journal of
Infectious Disease, 33, 10, 731-733.
Pothoulakis, C. (2001). Clostridium Difficile Infection. Participate. Retrieved March 1, 2006
from: http://www.aboutibs.org/Publications/CDifficile.html.
Rees, J., Davies, H.R., Birchall, C. & Price, J. (2000). Psychological Effects of Source
Isolation Nursing (2): Patient Satisfaction. Nursing Standard, 14, 32-36.)
REFERENCES
Rupnik, M., Dupuy, B. et al. (2005). Revised Nomenclature of Clostridium difficile Toxins
and Associated Genes. Journal of Medical Microbiology, 54, 113-117. Retrieved March 1,
2006 from: http://jmm.sgmjournals.org/cgi/content/full/54/2/113#F13
Stelfox, H.T., Bates, D.W. & Redelmeier, D.A. (2003) Safety of Patients Isolated for
Infection Control. Journal of the American Medical Association, 290, 1899-1905.
Sunenshine, R.H. & McDonald, L.C. (2006). Clostridium difficile-associated disease: New
challenges from an established pathogen. Cleveland Clinic Journal of Medicine, 73, 2.
Retrieved April 10, 2006 from:
www.cdc.gov/ncidod/dhqp/pdf/infDis/Cdiff_CCJM02_06.pdf
Tal, S., Gurevich, A., et al. (2002). Risk Factors for Recurrence of Clostridium difficileAssociated Diarrhea in the Elderly. Scandanavian Journal of Infectious Disease, 34, 8,
594-597.