Download clostridium difficile associated diarrhea

CLOSTRIDIUM DIFFICILE ASSOCIATED DIARRHEA
VALERIE FLETCHER, M.D.
INFECTIOUS DISEASES
SOUTHERN OHIO MEDICAL CENTER
August 2006
Introduction

Clostridium difficile is a Gram-positive, spore-forming
anaerobic bacillus.

Most common cause of nosocomial diarrhea.

Rate and severity of C. difficile-associated diarrhea
(CDAD) increasing.

New strain of C.difficile with increased resistance and
virulence identified.
History





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1893 – first case of pseudomembraneous colitis
reported as diphtheritic colitis.
1935 – “Bacillus difficile” isolated.
1970s – antibiotic-asociated colitis identified.
1978 – C. difficile toxins identified in humans.
1979 – therapy with vancomycin or metronidazole
2000 – increased incidence and virulence
Annual CDAD rates for hospitals with >500 beds (NNIS 1987 – 2001)
Estimates of US hospital discharges with CDAD
listed as any diagnosis
70
Discharges per 100,000
60
50
40
30
20
10
0
1996
1997
1998
1999
2000
2001
Years
Adapted from McDonald LC, et al. Annual
Meeting of IDSA, 2005
2002
2003
Epidemiology

Present in environment.

Hospital is major reservoir. Spores can be recovered
from surfaces for months.

Spread primarily on hands of HCW.

Fecal-oral transmission.

Transmission may occur from asymptomatic colonized
persons.
Epidemiology

Colonizes the colon of up to 3% of healthy adults.

15 – 25% of debilitated and antibiotic-treated
hospitalized adults colonized.

Toxigenic strains may cause disease in colonized
patients.

Implicated in approx. 25% of cases of antibioticassociated diarrhea
Clinical features

Mild disease – mild abdominal cramping pain.
- endoscopic findings of diffuse or patchy,
nonspecific colitis.

Moderate disease – fever, dehydration, nausea,
anorexia, malaise, profuse diarrhea,
abdominal distention and cramping
pain.
- moderate leukocytosis, fecal
leukocytes.
- diffuse, patchy colitis on endoscopy

Severe disease – usually profuse diarrhea, may be little
or no diarrhea.
- abdominal pain
- fever
- volume depletion
- marked leukocytosis
- peritoneal signs
- radiologic signs include ileus, dilated
colon and edematous colonic mucosa
- endoscopic findings of adherent yellow
plaques
Complications of CDAD

Pseudomembraneous colitis

Toxic megacolon

Perforation of the colon

Sepsis

Death
Patients at increased risk for disease
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
ANTIBIOTIC EXPOSURE
Gastrointestinal surgery or manipulation
Long length of stay in healthcare setting
Infected roommate
Co-morbid illnesses
Immunosuppression
Advanced age
Proton-pump inhibitors and H2-blockers?
Predictors of Severe Disease

Leukocytosis > 20,000

Increased creatinine above the baseline
Traditional list of Antibiotics associated with
CDAD
MORE FREQUENT
LESS FREQUENT
Cephalosporins (3rd and 4th generation)
Ticarcillin-clavulanate
Ampicillin/Amoxicillin
Metronidazole
Clindamycin
Fluoroquinolones
Other penicillins
Rifampin
Macrolides
5-Fluorouracil
Tetracyclines
Methotrexate
Trimethoprim-Sulfamethoxazole
Cyclophosphamide
Laboratory Diagnosis
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

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Stool culture
Latex agglutination to detect antigen in stools
Tissue culture assay for cytotoxicity of toxin B
Enzyme-linked immunosorbent assay (ELISA) for toxins
A and B
A new strain of C. difficile (NAP-1)

Toxinotype III
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Unsuppressed production of toxins A and B

Associated with presence of binary toxin.
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Increased resistance to clindamycin and
fluoroquinolones.

Potential for increased complications and adverse
outcome.
States with the North American Pulsed Field Type 1 strain of
C. difficile confirmed by CDC as of May 15, 2006 (N=17)
DC
HI
PR
AK
Adapted from L.C. McDonald, MD, CDC
Rate of antibiotic resistance in 91 C. difficile isolates from a Pittsburg
hospital that experienced a large CDAD outbreak beginning January 2000
Resistance (%)
100
90
80
70
60
50
40
30
20
10
0
Vancomycin
Metronidazole
Clindamycin
Muto CA, et al. Infect Control Hosp
Epidemiol 2005;26:273-280
Levofloxacin
The risk of CDAD and antibiotic use in a study of 1,703 patients from 12
Canadian hospitals
4
3.5
Odds Ratio
3
2.5
2
1.5
1
0.5
0
Cephalosporins Fluoroquinolones
Clindamycin
Loo VG, et al. NEJM 2005;353:2442-2449.
Macrolides
Number of inpatients tested and percentage of stools positive for
Clostridium difficile toxin at SOMC 2004 - 2006
300
Number of patients
250
200
150
100
50
0
J- F- M- A- M- J- J- A- S- O- N- D- J- F- M- A- M- J- J- A- S- O- N- D- J- F- M- A- M- J04 04 04 04 04 04 04 04 04 04 04 04 05 05 05 05 05 05 05 05 05 05 05 05 06 06 06 06 06 06
Time
Inpatient tested no.
Inpatient pos %
Linear (Inpatient tested no.)
Dr. T. Cassity, SOMC
Linear (Inpatient pos %)
Number of positive Clostridium difficile toxin tests
SOMC laboratory 2003 -2006
40
Number of positive tests
35
30
25
20
15
10
5
0
J- F- M- A- M- J- J- A- S- O- N- D- J- F- M- A- M- J- J- A- S- O- N- D- J- F- M- A- M- J- J- A- S- O- N- D- J- F- M- A- M- J03 03 03 03 03 03 03 03 03 03 03 03 04 04 04 04 04 04 04 04 04 04 04 04 05 05 05 05 05 05 05 05 05 05 05 05 06 06 06 06 06 06
TIME
Inpatient
Outpatients
Linear (Outpatients)
Dr. T. Cassity, SOMC
Linear (Inpatient)
CDAD - SOMC 2006

114 patients had C. difficile toxin detected in stools
between Jan 2006 – June 2006.

46 charts were available for review.
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31 (67%) patients were female.
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2 (4%) patients had recurrent CDAD.

13 (28%) patients did not receive a fluoroquinolone
during or immediately before admission.
Data from Marcie Malone, PharmD
candidate
Antibiotics associated with CDAD - SOMC 2006
Amp/Sulb
Clindamycin
Aztreonam
Tobromycin
Gentamicin
Linezolid
Ceftazidime
Azithromycin
Imipenem
Ertapenem
Cefazolin
Cefepime
Pip/Tazo
Ceftriaxone
Levofloxacin
0
5
10
15
20
25
Number of patients with positive C.difficile toxin
Data from Marcie Malone, PharmD
candidate
30
35
Ceftriaxone and Levofloxacin use – SOMC, Jan – Aug 2006
9000
Number of patients
8000
7000
6000
5000
4000
3000
2000
1000
0
Ceftriaxone
IV Levofloxacin
Oral
Levofloxacin
Antibiotics dispensed
Proton Pump Inhibitors, H2-blockers and C.difficile toxin
detection – SOMC 2006
Famotidine
Lansoprazole
Esomeprazole
0
5
10
15
20
Number of patients with positive C.difficle toxin
Data from Marcie Malone. PharmD
candidate
25
Management
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Enhanced infection control measures.
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Targeted antibiotic restriction
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Appropriate antibiotic therapy
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Adjunctive therapy – probiotics, IVIG, toxin binders
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Surgery

Avoid antiperistaltic and opiate drugs.

Experimental therapy – rifaximin, tolevamar,
corticosteroids, vaccine, monoclonal antibodies to toxins
A and B, non-toxigenic C,difficile
Antibiotic Therapy

Oral therapy – vancomycin, metronidazole
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Unable to tolerate oral therapy – IV metronidazole,
vancomycin via NG tube or enema.
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Vancomycin + rifampin
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Less frequently used – Bacitracin, fusidic acid
Antibiotic therapy for CDAD
Metronidazole
Vancomycin
Route
Oral or IV
Oral only
Dose
250 – 500 mg q8h or q6h 125 – 500 mg q6h
Response rate
94%
94%
Duration
10 – 14 days
10 – 14 days
Cost
$20
$200 - $800
Recurrence rate
20%
19%
Indications for Vancomycin therapy
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No response to metronidazole
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Metronidazole intolerance
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Pregnancy and child < 10 yrs
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Severe/fulminant CDAD
Conclusion

Increasing numbers and severity of CDAD.

Active surveillance recommended.

Early diagnosis and treatment are important for reducing
severe outcome.

Judicious use of antibiotics may reduce incidence of
CDAD
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Strict infection control practices essential.