Transcript Clostridium difficile Infection (CDI)

SENIOR RESEARCH PROJECT
The Increased Use of Broad Spectrum
Antimicrobials and the Increased Incidence
of Clostridium difficile Infection (CDI)
Maisara Rahman, MD
Suzette Jumamil MD
Soheil Samvatian MD
Trena Rich, MSN, ARNP, CIC
BACKGROUND



Clostridium difficile infection (CDI) is becoming one of the
most common healthcare associated infection (HAI) in the
United States [1]
Emergence of new strain of C. difficile (BI/NAP1 (North
American Pulse type 1)/027) is associated with
increased virulence and severity of CDI [13]
Variety of coalescing causes increase incidence of CDI
 Increasing age of US population
 Increase use of antimicrobials
 Inadequate CDI infection control measures
delayed diagnosis, poor hand hygiene, environmental
cleaning [1,2,3,4,5]
BACKGROUND
(CONT’D)

CDI is a frequent cause of morbidity and mortality
 2.3% (overall unadjusted)
 6.1% ( ICU CDI)
 25% Mortality rate in elderly patients who
are frail

CDI causes increased hospital stays


an average of 3.6 days
Cost > 1.1 billion dollars/ year
EPIDEMIOLOGY
States with BI/NAP1/027 strain of C.
difficile (N=38), November 2007
DC
•Changing rapidily and has
been marked by significant
increase in incidence and
and severity
AK
www.cdc.gov/ncidod/dhqp/id_Cdiff)_data.html
HI
PR
States with BI/NAP1/027 strain of
C. difficile (N=40), October 2008
DC
AK
HI
PR
There is a common
epidemic HVS that
continues to be reported
from hospitals in an
exapanding # states
Epidemic strain Produces 16 fold higher concentration of TOXIN A &
secretes 23 X higher concentration toxin B & binary toxin associated with severe diarrhea
Medical Center C. difficile Rates
2005-2009
5.00
CDI Rates per 10,000 discharges
2005
4.50
2006
4.00
2007
3.50
2008
3.00
2009
2.50
2.00
1.50
1.00
0.50
0.00
HAI
Community
OBJECTIVE
To Determine the incidence , risk
factors, and outcomes of CDI as it
relates to the use of broad spectrum
antimicrobial agents at a Riverside
County Regional Medical Center
HYPOTHESIS
The increased rates and severity
of CDI is due to the increased use
of a variety of broad spectrum
antimicrobial agents.
Key Points on C. difficile

Motile, gram positive spore
forming bacillus
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

Obligate anaerobe
Ubiquitous in nature
Produce Toxins :
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Enterotoxin (Toxin A)
Cytotoxin ( Toxin B)
Binary Toxin ( BI/NAP1/027virulent-strain)
Microscopically: long, irregular, with
sub-terminal non-staining spores
Color-enhanced scanning electron micrograph by McCarthy and Cavangh
BI/NAP1/027 strain of
C. difficile
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Deletion in the pathogenicity locus gene, tcdC,
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A deletion in gene tcdC is a proposed negative regulator of the
production of toxins A and Bthat might result in increased
concentration of toxins A & B
Key Points on C. difficile
(cont’d)

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It forms part of the normal intestinal
flora in children less than one year
old
Associated with a spectrum of
diseases ranging from asymptomatic
colonization to severe diarrhea, toxic
megacolon, sepsis and death
MODE OF TRANSMISSION

Transmission is via:
Fecal-oral route
 Can occur from patient to patient from
contaminated environment (i.e., hands
of HCW's)
 C. difficile spores are more resistant to
a variety of chemical disinfectants
 C. difficile spores can survive up to 5
months

Antibiotics disrupt flora
Pathogenicity Starts With Disruption
of Normal Protective Colonic Flora
Followed By Ingestion of C. difficile Spores
Uncontrolled Proliferation & Colonization With Toxigenic C.D.I
Release of Toxin A (enterotoxin )/ B (cytotoxin)
Toxins Bind to Colonic Epithelial Cells
causing
Mucosal injury, Inflammation,
Cytoskeletal damage
Pathogenesis of Clostridium difficile-associated diarrhea in adults
Poutanen, S. M. et al. CMAJ 2004;171:51-58
Copyright ©2004 Canadian Medical Association or its licensors
Endoscopic View of C. difficile
Pathology of Clostridium difficile
RAISED ADHERENT YELLOW PLAQUES
VARY IN SIZE FROM 2 MM TO 10 MM
VISIBLE ON COLONIC MUCOSA
PSEUDOMEMBRANOUS COLITIS:
 Characteristic manifestation of full-blown
Clostridium difficile colitis
More severe lesion shows an
inflammatory infiltrate and
pseudomembrane
Classic pseudomembranes are visible as raised
yellow plaques ranging from 2-10 mm in
diameter and scattered over the colorectal
mucosa
Endoscopic visualization of Courtesy of Gregory Ginsberg, MD, University of Pennsylvania/ Source: www.uptodate.com
Barium Enema Result
Pseudomembranous colitis:
Demonstrating typical serrated appearance from trapped barium between
the edematous mucosal folds and the plaque- like membranes
STUDY METHODS
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A Retrospective study of 69 patients with
CDI who had a diagnostic code for C.
difficile colitis at the time of hospital
discharge and all patients who otherwise
had positive cytotoxin assays or pathology
reports (January 2007-April, 2009)
A detailed Computer directed-chart review
through the RCRMC Infection Prevention &
Control Data was analyzed.
No children were included in this study.
STUDY METHODS
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(cont’d)
Data reviewed included:
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Admitting History and Physical
examinations
Daily Progress notes
RCRMC Pharmacy records for antimicrobials
used on each patient & computerized
review of all written antimicrobials usage at
RCRMC from 12/08-3/09
Discharge summary reports
DATA ANALYSIS:
Demographics
120
100
80
60
Series1
40
20
0
MALES
FEMALES
WEIGHT kg
HEIGHT cm
BMI
Demographics: Age Range
90-100
80-89
70-79
60-69
50-59
40-49
30-39
20-29
<19
0
5
10
15
20
Pr
ev
iou
s
F
DM
F
di
ff
CH
C
CR
pr
om
is e
Hx
Im
m
un
oc
om
M
al
ign
an
cy
No
ne
Co-Morbidities
25
20
15
10
5
0
Nutrition
40
35
30
25
20
15
10
5
0
TPN
Tube Feedings
Regular Diet
Antimicrobials Taken Up to
8 Weeks Prior to Symptoms
50
45
40
35
30
25
20
15
10
5
Broad
Spectrum
Antifungals
FQ
Cephalosporins
Carbapenems
Beta lactams
0
Other Medications Up to 8
Weeks of Symptom Onset
20
18
16
14
12
10
8
6
4
Antidiarrheal
Coumadin
Corticosteroids
Other Antacids
H2 Blockers
0
PPI
2
Surgeries
20
18
16
14
12
10
8
6
4
2
0
Prior to 6 w eeks
Abdominal
Colectomy due to C diff
0
No
documentation
No Diarrhea
Fever
Co-infection
Abdominal Pain
CT evidence of
Colitis
Ileus
Bloody
Diarrhea
Diarrhea
Clinical Symptoms/Findings
60
50
40
30
20
10
nia
El
ev
at
ed
Cr
ea
t
BU
N
al
bu
m
in
El
ev
at
ed
Lo
w
Th
ro
m
bo
cy
to
s is
Th
ro
m
bo
cy
to
pe
Lab Analysis
80
70
60
50
40
30
20
10
0
Treatment for Laboratory
Confirmed C. difficile
50
45
40
35
30
25
20
15
10
5
0
PO Flagyl
IV Flagyl
PO Vanco
IV Vanco
Bactrim
None
Select Antimicrobial Usage
All ICUs Dec 08- Mar 09
300
NHSN Mean
250
08-Dec
09-Jan
09-Feb
200
09-Mar
150
100
Vanco-IV
Vanco-PO
Fluoroquinolones
Antistaphylococcal
PCN
Antipsudomonal
PCN
0
Trimeth/Sulfameth
50
Riverside County Regional Medical Center Infection Prevention and Control & Pharmacy Departments, and the Centers for
Disease Control & Prevention, National Healthcare Safety Network Program
Select Antimicrobial Usage
All Non- ICUs Dec 08- Mar 09
140
NHSN Mean
120
08-Dec
09-Jan
100
09-Feb
09-Mar
80
60
40
Vanco-IV
Vanco-PO
Fluoroquinolones
Antistaphylococcal
PCN
Antipsudomonal
PCN
0
Trimeth/Sulfameth
20
Analysis of Antimicrobial
Utilization
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Compared to the National Healthcare
Safety Network (NHSN), RCRMC is in
the 97th percentile in prescribing
Antipseudomonal Penicillins
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With a p-value of (0.000)
RCRMC is in the 65th percentile of
NHSN in prescribing Fluoroquinolones.
Retrospective Case-Control Study of the Effect of Fluoroquinolone
on CDAD (Level II-2 Evidence)
Study
McCusker
2003
Univ. of
Maryland
Risk Factor
Fluoroquinolones
Odds
Ratio
12.7
95% CI
2.6. to 61.1
Clindamycin
0.4
0.1 to 1.5
Piperacillin/
tazobactam
2.2
0.5 to 9.1
Cephalosporins
0.6
0.2 to 1.7
McCusker et al., Emerg Infect Dis. 2003 June; 9(6):730-3
Comments
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Cases (n=30) VS controls (n=60)
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Exposure to Fluoroquinolones was
an independent risk factor
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Restricted use of levofloxacin and
other implicated antibiotics may be
required to control outbreak
Summation
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Based on our data analysis the increased
rates and severity of CDI is caused by
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The increased use or over use of broad
spectrum antibiotics
Not following current treatment guidelines for
CDI
Lack of adherence in following infection
prevention & control practices
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All of the above can increase the cost of healthcare
delivery
CONCLUSION
The Data supports our hypothesis
that there is an increase in the
incidence of CDI secondary to
the increased use of broad
spectrum antimicrobial agents
Recommendations
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Implement a new system with Pharmacy
and Physicians, for the monitoring and
control of antimicrobial utilization
Reinforce the use of the current “Antibiotic
Automatic Stop System”
Reduce the use of prophylaxis
antimicrobial agents
Decrease the use of empiric antimicrobial
agents
Recommendations
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Hand Hygiene with
soap and water only
Spores only killed by
Sodium hypochlorite
(bleach), not killed
by alcohols or
detergents
Follow Transmission
based isolation
precautions
Think it about it…..
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If you have a patient with albumin
levels that are trending downward,
would you want to monitor the use of
antimicrobial agents???
Consider patients on PPI & H2Blockers, at a higher risk for CDI
References
Bartlett JG. Antibiotic-associated diarrhea. N Engl J Med 2002;346:334-339. [
2.
Bartlett JG, Onderdonk AB, Cisneros RL, Kasper DL. Clindamycin-associated colitis due to a toxin-producing species of
Clostridium in hamsters. J Infect Dis 1977;136:701-705. [
3.
Bartlett JG, Chang T, Taylor NS, Onderdonk AB. Colitis induced by Clostridium difficile. Rev Infect Dis 1979;1:370-378. ]
4.
Taylor NS, Bartlett JG. Partial purification and characterization of a cytotoxin from Clostridium difficile. Rev Infect Dis
1979;1:379-385. [
5.
Taylor NS, Thorne GM, Bartlett JG. Comparison of two toxins produced by Clostridium difficile. Infect Immun
1981;34:1036-1043.
6.
Johal SS, Hammond J, Solomon K, James PD, Mahida YR. Clostridium difficile associated diarrhoea in hospitalized
patients: onset in the community and hospital and role of flexible sigmoidoscopy. Gut 2004;53:673-677.
7.
Johnson S, Samore MH, Farrow KA, et al. Epidemics of diarrhea caused by a clindamycin-resistant strain of Clostridium
difficile in four hospitals. N Engl J Med 1999;341:1645-1651. [
8.
Rubin MS, Bodenstein LE, Kent KC. Severe Clostridium difficile colitis. Dis Colon Rectum 1995;38:350-354. [
9.
Kyne L, Hamel MB, Polavaram R, Kelly CP. Health care costs and mortality associated with nosocomial diarrhea due to
Clostridium difficile. Clin Infect Dis 2002;34:346-353.
10. Archibald LK, Banerjee SN, Jarvis WR. Secular trends in hospital-acquired Clostridium difficile disease in the United States,
1987-2001. J Infect Dis 2004;189:1585-1589. [
11. McDonald LC, Banerjee S, Jernigan DB. Increasing incidence of Clostridium difficile-associated disease in U.S. acute care
hospitals, 1993-2001. In: Proceedings of 14th Annual Scientific Meeting of the Society for Healthcare Epidemiology
12. Dallal RM, Harbrecht BG, Boujoukas AJ, et al. Fulminant Clostridium difficile: an underappreciated and increasing cause of
death and complications. Ann Surg 2002;235:363-372. [
13. L. Clifford McDonald, M.D., George E. Killgore, Dr.P.H., Angela Thompson, M.M.Sc., Robert C. Owens, Jr., Pharm.D.,
Sophia V. Kazakova, M.D., M.P.H., Ph.D., Susan P. Sambol, M.T., Stuart Johnson, M.D., and Dale N. Gerding, M.D. An
epidemiology toxin gene variant strain of C. difficle. Abstract. Philadelphia.
END!
Updated SHEA-IDSA recommendations for the treatment of CDI
stratified by disease incidence and severity
Clinical definition
Supportive clinical data
Recommended
treatment
Initial episode
Mild or moderate
WBC < 15,000 cells/mm2 Oral Metronidozale 500
Cr level < 1.5 x prior CDI mg TID x 10-14 days
A-I
Initial episode
Severe
WBC > 15,000 cells/mm2
Cr level > 1.5 prior CDI
Oral Vanco 125 mg QID
x 10 n-14 days
B-I
Initial episode
complicated
Hypotension or shock,
mega colon, perforation,
severe colitis on CT scan
If no complete ileus:
Vanco 500 mg QID
Oraly or via NGT and/or
Metronidazole 500mg 750 mg IV q 8 hrs
C-II
First recurrent
Same as for initial
episode
A-II
Second recurrence
or further
recurrence
Oral Vancomycin taper
with or without Pulse
dosing
B-II
Adapted from the Latest Advances in Closridium difficile, 45th IDSA and 47th ICAAC meeting
Strength
Treatment Options
for
C. difficile infection
Jaber et al Am J Gastroenterol 2008; 103:3195–3203