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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 (enter by clicking on arrow to the right). Welcome….

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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

(enter by clicking on arrow to the right)

welcome
Welcome…

To navigate this tutorial, these tools are available:

will move you FORWARD to the next page.

will move you BACK one page.

A highlighted area will move you to related articles, websites, or glossary definitions

will RETURN you to the “click here”

“TABLE OF CONTENTS”.

Permission for use of information from this web-based tutorial must be obtained from the author at 4under1roof@sbcglobal.net.

(Navigation symbols from Microsoft Office 2003)

click a subject below to learn more about
“CLICK” A SUBJECT BELOW TO LEARN MORE ABOUT…

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

(CLICKING ON “ ” WILL RETURN YOU HERE AT ANY TIME)

how is c difficile spread
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)

slide5
NO….

NOT AN INHALED BACTERIUM!

…try again!!

(click HERE to try again)

slide6
NO…

…IT’S NOT A VIRUS

…try again!!

(click HERE to try again)

slide7
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
Pathophysiology of C-difficile

Sunenshine & McDonald (2006)

www.cdc.gov/ncidod/dhqp/pdf/infDis/Cdiff_CCJM02_06.pdf

(picture used with permission)

slide9

Sunenshine & McDonald (2006)

www.cdc.gov/ncidod/dhqp/pdf/infDis/Cdiff_CCJM02_06.pdf

(Picture used with permission)

pathophysiology of c difficile10
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:

Normal Flora must be disrupted (occurs with antibiotics).

Clostridium difficile must be ingested.

(These do not have to occur in this order)

The Onset of Pseudomembraneous Colitis

Sunenshine & McDonald (2006)

www.cdc.gov/ncidod/dhqp/pdf/infDis/Cdiff_CCJM02_06.pdf

(picture used with permission)

slide12
“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
ACTUAL ENDOSCOPY PICTURES:

picture courtesy of Carol Hein, RN, MSN (used with permission)

slide14
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
WHICH OF THESE PRODUCES THE DIARRHEA SYMPTOMS OF C-DIFF?

TOXINS “TD-1” AND “TD-2”

TOXINS “A” AND “B”

TOXINS “C” AND “DIFF”

slide16
NO !

TRY ANSWERING AGAIN!

slide17
YES…

YOU GOT IT !!

Sunenshine & McDonald (2006)

(picture used with permission)

history of c diff
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
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

slide20
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
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
THE RESULT:
  • SEVERE CASES: PSEUDOMEMBRANEOUS COLITIS, LEADING TO:

TOXIC MEGACOLON

…AND ULTIMATELY,

. . . . DEATH!!!

fulminant colitis
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
PATIENT PRESENTATION
  • USUALLY HAVE HAD ANTIBIOTICS OR ANTINEOPLASTICS IN PAST 2 MONTHS
  • SOME COMMON ANTIBIOTICS THAT CONTRIBUTE TO C-DIFF INCLUDE:
  • AMPICILLIN
  • AMOXACILLIN
  • CEPHALOSPORINS
  • CLINDAMYCIN

Pothoulakis (2001)

http://www.aboutibs.org/Publications/CDifficile.html

(picture: Microsoft Office 2003)

top 4 causes of cross contamination
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
THE NUMBER ONE REASON:(click the picture)

(picture: Microsoft Office 2003)

did you know
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 result29
THE RESULT…
  • LONGER HOSPITALIZATIONS
  • CHRONIC DIARRHEA IN SOME ELDERLY
  • SERIOUS / LIFE THREATENING DISEASE

Stelfox, Bates, & Redelmeier (2003)

slide30

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
Toxin “A” & the Neurokinin-1 Receptor

STUDIES WITH LABORATORY MICE HAVE SHOWN:

  • TOXIN “A” BINDS TO THE NEUROKININ-1 (NK-1) RECEPTOR IN THE INTESTINAL LINING.
  • THE FAMILY OF Rho PROTEINS (PROTEINS INVOLVED IN CELLULAR FUNCTION) IS INACTIVATED.
  • 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
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
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
TO SUMMARIZE THE GENETICS PROCESS:
  • Toxin “A” binds to the Neurokinin-1 (NK-1) receptors of the intestinal linings.
  • Rho Proteins become inactivated & Actin Microfilaments become disaggregated, essentially breaking down the cell.
  • Toxin “A” stimulates Substance“P”, causing nausea, pain, & vasodilation.
  • Macrophages and Leukocytes complete the inflammatory intestinal lining damage.
  • Toxin “A” needs Substance “P” in a cause-

effect relationship, or damage is diminished.

enter the new c diff strain
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 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
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
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
The Latest Treatment Recommended:

Sunenshine & McDonald (2006)

www.cdc.gov/ncidod/dhqp/pdf/infDis/Cdiff_CCJM02_06.pdf

(table from article used with permission)

it can come back
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)

those most susceptible
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
HIGHEST RISK GROUPS:
  • OLDER PATIENTS
  • CHRONIC RENAL FAILURE PATIENTS
  • PATIENTS WITH NASOGASTRIC FEEDING TUBES
  • PATIENTS WITH A C-DIFF HISTORY

THIS IS DUE TO “PHYSIOLOGICAL

AND FUNCTIONAL CHANGES OF

THE GUT”, WHICH “ARE OFTEN

ACCOMPANIED BY AN INCREASED INCIDENCE OF GASTROINTESTINAL INFECTIONS”

(picture: Microsoft Office 2003)

adverse effects of contact isolation
PATIENTS IN ISOLATION

3.9 ROOM ENTRIES/HOUR.

2.1 MEAN CONTACTS/HR

BY A REGISTERED NURSE.

4.5 MINUTES OF ACTUAL HEALTHCARE WORKER INTERVENTION TIME PER

OCCURANCE.

Kirkland & Weinstein (1999)

PATIENTS NOT IN ISOLATION

7.9 ROOM ENTRIES/HOUR.

4.2 MEAN CONTACTS/HR

BY A REGISTERED NURSE.

2.8 MINUTES OF ACTUAL HEALTHCARE WORKER INTERVENTION TIME PER

OCCURANCE.

“ADVERSE EFFECTS OF CONTACT ISOLATION”

(picture: Microsoft Office 2003)

hospital patients in isolation receive inferior care study says
“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
“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)

slide49

Sunenshine & McDonald (2006)

(picture from article used with permission)

references
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

references52
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.)

references53
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 difficile-Associated Diarrhea in the Elderly. Scandanavian Journal of Infectious Disease, 34, 8, 594-597.