SENIOR RESEARCH PROJECT The Increased Use of Broad Spectrum Antimicrobials and the Increased...
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SENIOR RESEARCH PROJECT
The Increased Use of Broad Spectrum Antimicrobials and the Increased Incidence
of Clostridium difficile Infection (CDI)
Maisara Rahman, MDSuzette Jumamil MDSoheil Samvatian MDTrena 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. difficileC. difficile (BI/NAP1 (North (BI/NAP1 (North American Pulse type 1)/027) is associated with American Pulse type 1)/027) is associated with increased virulence 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
States with BI/NAP1/027 strain of States with BI/NAP1/027 strain of C. C. difficiledifficile (N=38), November 2007 (N=38), November 2007
DC
PRAKHI
www.cdc.gov/ncidod/dhqp/id_Cdiff)_data.html
EPIDEMIOLOGY
•Changing rapidily Changing rapidily and has been and has been marked by marked by significant increase significant increase in incidence and in incidence and and severityand severity
States with BI/NAP1/027 strain of States with BI/NAP1/027 strain of C. C. difficiledifficile (N=40), October 2008 (N=40), October 2008
DC
PRAK
HI
There is a There is a common epidemic common epidemic HVS that HVS that continues to be continues to be reported from reported from hospitals in an hospitals in an exapanding # exapanding # statesstates
Medical Center C. difficile Rates 2005-2009
CDI Rates per 10,000 discharges
0.00
0.50
1.00
1.50
2.00
2.50
3.00
3.50
4.00
4.50
5.00
HAI Community
2005
2006
2007
2008
2009
OBJECTIVEOBJECTIVE
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
HYPOTHESISHYPOTHESIS
The increased rates and severity The increased rates and severity of CDI is due to the increased use of CDI is due to the increased use
of a variety of broad spectrum of a variety of broad spectrum antimicrobial agents. antimicrobial agents.
Color-enhanced scanning electron micrograph by McCarthy and CavanghColor-enhanced scanning electron micrograph by McCarthy and Cavangh
Key Points on Key Points on C. difficileC. difficile Motile, Motile, gram positive gram positive
spore forming spore forming bacillusbacillus
Obligate anaerobeObligate anaerobe Ubiquitous in natureUbiquitous in nature Produce ToxinsProduce Toxins : :
EnterotoxinEnterotoxin ( (Toxin A)Toxin A)
Cytotoxin Cytotoxin ( Toxin B)( Toxin B)
Binary ToxinBinary Toxin ( ( BI/NAP1/027BI/NAP1/027virulent-virulent-strainstrain))
Microscopically: long, irregular, Microscopically: long, irregular, with sub-terminal non-staining with sub-terminal non-staining sporesspores
BI/NAP1/027 strain of BI/NAP1/027 strain of C. difficileC. difficile
Deletion in the pathogenicityDeletion in the pathogenicity locus gene, locus gene, tcdC,tcdC, A deletion in gene A deletion in gene tcdCtcdC is a proposed negative regulator of the is a proposed negative regulator of the
productionproduction of toxins A and Bof toxins A and Bthat might result in increased that might result in increased concentration of toxins A & B concentration of toxins A & B
Key Points on Key Points on C. difficileC. difficile (cont’d)(cont’d)
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 TRANSMISSIONMODE OF TRANSMISSION
Transmission is via:Transmission is via: Fecal-oral routeFecal-oral route Can occur from patient to patient from Can occur from patient to patient from
contaminated environment (i.e., hands contaminated environment (i.e., hands of HCW's) of HCW's)
C. difficileC. difficile spores are more resistant to a spores are more resistant to a variety of chemical disinfectants variety of chemical disinfectants
C. difficile C. difficile spores can survive up to 5 spores can survive up to 5 monthsmonths
Pathogenicity Starts With Pathogenicity Starts With Disruption of Normal Disruption of Normal
Protective Colonic FloraProtective Colonic Flora
Toxins Bind to Colonic Toxins Bind to Colonic Epithelial Cells Epithelial Cells causingcausing
Mucosal injury, Inflammation, Mucosal injury, Inflammation, Cytoskeletal damageCytoskeletal damage
Antibiotics disrupt flora
Followed By Ingestion of C. difficile Spores
Uncontrolled Proliferation & Colonization With Uncontrolled Proliferation & Colonization With Toxigenic Toxigenic C.D.IC.D.I
Release of Toxin A (enterotoxin )/ B Release of Toxin A (enterotoxin )/ B (cytotoxin)(cytotoxin)
Copyright ©2004 Canadian Medical Association or its licensors
Poutanen, S. M. et al. CMAJ 2004;171:51-58
Pathogenesis of Clostridium difficile-associated diarrhea in adults
Endoscopic View of Endoscopic View of C. difficileC. difficile
Pathology of Clostridium difficile
RAISED ADHERENT YELLOW PLAQUES VARY IN SIZE FROM 2 MM TO 10 MM
VISIBLE ON COLONIC MUCOSA
More severe lesion shows aninflammatory infiltrate and pseudomembrane
PSEUDOMEMBRANOUS COLITIS: Characteristic manifestation of full-blown Clostridium difficile colitis
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 METHODSSTUDY METHODS A Retrospective study of 69 patients with A Retrospective study of 69 patients with
CDI who had a diagnostic code for CDI who had a diagnostic code for C. difficileC. difficile colitis at the time of hospital discharge and colitis at the time of hospital discharge and all patients who otherwise had positive all patients who otherwise had positive cytotoxin assays or pathology reports cytotoxin assays or pathology reports (January 2007-April, 2009)(January 2007-April, 2009)
A detailed Computer directed-chart review A detailed Computer directed-chart review through the RCRMC Infection Prevention & through the RCRMC Infection Prevention & Control Data was analyzed. Control Data was analyzed.
No children were included in this study.No children were included in this study.
STUDY METHODS (cont’d)
Data reviewed included:Data reviewed included: Admitting History and Physical Admitting History and Physical
examinationsexaminations Daily Progress notesDaily Progress notes RCRMC Pharmacy records for RCRMC Pharmacy records for
antimicrobials used on each patient & antimicrobials used on each patient & computerized review of all written computerized review of all written antimicrobials usage at RCRMC from 12/08-antimicrobials usage at RCRMC from 12/08-3/09 3/09
Discharge summary reportsDischarge summary reports
DATA ANALYSIS:DATA ANALYSIS: DemographicsDemographics
Demographics: Age Range
0 5 10 15 20
<19
20-29
30-39
40-49
50-59
60-69
70-79
80-89
90-100
Co-Morbidities
0
5
10
15
20
25
Nutrition
0
5
10
15
20
25
30
35
40
TPN Tube Feedings Regular Diet
Antimicrobials Taken Up to 8 Weeks Prior to Symptoms
0
5
10
15
20
25
30
35
40
45
50
Bet
a la
ctam
s
Car
bape
nem
s
Cep
halo
spor
ins FQ
Ant
ifung
als
Bro
adS
pect
rum
Other Medications Up to 8 Weeks of Symptom Onset
0
2
4
6
8
10
12
14
16
18
20
PP
I
H2
Blo
cker
s
Oth
er A
ntac
ids
Cor
ticos
tero
ids
Cou
mad
in
Ant
idia
rrhe
al
Surgeries
0
2
4
6
8
10
12
14
16
18
20
Prior to 6 w eeks Abdominal Colectomy due to C diff
Clinical Symptoms/Findings
0
10
20
30
40
50
60
Dia
rrhe
a
Blo
ody
Dia
rrhe
a
Ileus
CT
evi
denc
e of
Col
itis
Abd
omin
al P
ain
Co-
infe
ctio
n
Fev
er
No
Dia
rrhe
a
No
docu
men
tatio
n
Lab Analysis
0
10
20
30
40
50
60
70
80
Treatment for Laboratory Confirmed C. difficile
0
5
10
15
20
25
30
35
40
45
50
PO Flagyl IV Flagyl PO Vanco IV Vanco Bactrim None
Select Antimicrobial Usage Select Antimicrobial Usage All ICUs Dec 08- Mar 09All ICUs Dec 08- Mar 09
0
50
100
150
200
250
300
Antip
sudom
onal
PC
N
Antis
taphylo
coccal
PC
N
Flu
oro
quin
olo
nes
Trim
eth
/Sulfa
meth
Vanco-P
O
Vanco-I
V
NHSN Mean
08-Dec
09-Jan
09-Feb
09-Mar
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 Select Antimicrobial Usage All Non- ICUs Dec 08- Mar 09All Non- ICUs Dec 08- Mar 09
0
20
40
60
80
100
120
140
Ant
ipsu
dom
onal
PC
N
Ant
ista
phyl
ococ
cal
PC
N
Flu
oroq
uino
lone
s
Trim
eth/
Sul
fam
eth
Van
co-P
O
Van
co-I
V
NHSN Mean
08-Dec
09-Jan
09-Feb
09-Mar
Analysis of Antimicrobial Utilization
Compared to the National Healthcare Safety Network (NHSN), RCRMC is in the 97th percentile in prescribing Antipseudomonal Penicillins With a With a p-value of (0.000)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 Risk Factor
Odds Ratio 95% CI Comments
McCusker
2003
Univ. of Maryland
Fluoroquinolones 12.7 2.6. to 61.1 Cases (n=30) VS controls (n=60)
Exposure to Fluoroquinolones was
an independent risk factor
Restricted use of levofloxacin and
other implicated antibiotics may be
required to control outbreak
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
SummationSummation
Based on our data analysis the increased Based on our data analysis the increased rates and severity of CDI is caused byrates and severity of CDI is caused by The increased use or over use of broad The increased use or over use of broad
spectrum antibioticsspectrum antibiotics Not following current treatment guidelines for Not following current treatment guidelines for
CDICDI Lack of adherence in following infection Lack of adherence in following infection
prevention & control practicesprevention & control practices
All of the above can increase the cost of healthcare All of the above can increase the cost of healthcare deliverydelivery
CONCLUSIONCONCLUSION
The Data supports our hypothesis The Data supports our hypothesis that there is an increase in the that there is an increase in the incidence of CDI secondary to incidence of CDI secondary to
the increased use of broad the increased use of broad spectrum antimicrobial agentsspectrum antimicrobial agents
Recommendations
Implement a new system with Pharmacy Implement a new system with Pharmacy and Physicians, for the monitoring and and Physicians, for the monitoring and control of antimicrobial utilizationcontrol of antimicrobial utilization
Reinforce the use of the current “Antibiotic Reinforce the use of the current “Antibiotic Automatic Stop System” Automatic Stop System”
Reduce the use of prophylaxis Reduce the use of prophylaxis antimicrobial agentsantimicrobial agents
Decrease the use of empiric antimicrobial Decrease the use of empiric antimicrobial agentsagents
Recommendations
Hand Hygiene with Hand Hygiene with soap and water onlysoap and water only
Spores only killed by Spores only killed by Sodium hypochlorite Sodium hypochlorite (bleach), (bleach), not killed not killed by by alcohols or alcohols or detergentsdetergents
Follow Transmission Follow Transmission based isolation based isolation precautionsprecautions
Think it about it…..
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 & H2-Blockers, at a higher risk for CDI
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. 13. L. Clifford McDonald, M.D., George E. Killgore, Dr.P.H., Angela Thompson, M.M.Sc., Robert 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., 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 Stuart Johnson, M.D., and Dale N. Gerding, M.D. An epidemiology toxin gene variant strain of C. difficle. C. difficle. Abstract. Philadelphia.Abstract. Philadelphia.
References
END!
Updated SHEA-IDSA recommendations for the treatment of CDI stratified by disease incidence and severity
Clinical definition Supportive clinical data Recommended treatment
Strength
Initial episode Mild or moderate
WBC < 15,000 cells/mm2
Cr level < 1.5 x prior CDIOral Metronidozale 500 mg TID x 10-14 days
A-I
Initial episode Severe
WBC > 15,000 cells/mm2
Cr level > 1.5 prior CDIOral 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
Treatment Options for
C. difficile infection
Jaber et al Am J Gastroenterol 2008; 103:3195–3203