This is an abbreviated version of the

PowerPoint presentation

that accompanied the CDC's

Sept 16, 2008

COCA Conference Call.

For the full presentation, visit

http://www.emergency.cdc.gov/coca/callinfo.asp

(This version should not be used as a basis for making decisions about diagnosis or infection control.)

Changing Epidemiology and Prevention of Clostridium difficile

Carolyn Gould, MD, MSDivision of Healthcare Quality Promotion

Clinician Outreach and Communication ActivitySeptember 16, 2008

The findings and conclusions in this presentation are those of the author and do not necessarily represent the views of the Centers for Disease Control and Prevention

No Conflicts of Interest to Disclose

Prerequisites for CDI

Antimicrobial therapy

Disturbed colonic microflora

• Advanced age• Underlying illness

CDI

Acquisition of toxigenic C. difficile

Toxin A & Toxin B production

• CDI due to recent (re)acquisition of C. difficile• Incubation period unknown• <7 days to several weeks?

• Antimicrobial exposure may or may not precede acquisition• The two appear to be in proximity

Changing Epidemiology of CDI

• Increasing incidence and severity– Based on NNIS, national hospital discharge data,

reports from healthcare systems, death certificate data

• Recent outbreaks of severe disease caused by epidemic strain of C. difficile with increased virulence, antibiotic resistance

• Although elderly are still most greatly affected, more disease reported in “low-risk” persons– Healthy persons in community, peripartum women

Outcomes of CDIin Setting of Endemic Disease

Dubberke ER, et al. Clin Infect Dis. 2008;46:497-504.Dubberke ER, et al. 17th Annual Meeting of The Society for Healthcare Epidemiology of America (SHEA), April 14-17, 2007; Baltimore, MD. Unpublished data.

• Excess costs– $2,380 to $3,240 per index hospitalization– $3,797 to $7,179 inpatient costs over 180 days of

follow-up

• Other outcomes– 2.8 days attributable excess length of stay– 19.3% attributable readmission (180 days)– 5.7% attributable mortality (180 days)– More likely discharged to long-term care

How important are asymptomatic carriers in transmission?

Riggs MM et al. Clin Infect Dis 2007; 45:992–8

Rationale to consider extending isolation beyond duration of diarrhea

Bobulsky GS et al. Clin Infect Dis 2008; 46:447–50

Environmental control: Effect of hypochlorite in highly

endemic ward

Mayfield JL. Clin Infect Dis 2000;31:995–1000

Novel Risk Factors, Washington University Prevention Epicenter (n=36,086)

0.5 (0.3–0.6) Metronidazole

1.9 (1.3–2.7) IV vancomycin, >7 days

2.5 (1.8–3.5) Fluoroquinolones, >7 days

1.6 (1.3–2.1) Proton pump inhibitors

2.0 (1.6–2.5) Histamine-2 blockers

Medications

4.0 (2.9–5.6) >1.4

2.9 (2.1–4.2) 0.3–1.4

Reference <0.03

C. difficile-associated disease pressure

OR (95% CI)Risk Factor by Multivariable Analysis

CI=confidence interval; IV=intravenous; OR=odds ratio.Dubberke ER, et al. Clin Infect Dis. 2007;45:1543-1549.

Quinolone Restriction Period

Nim

ber

of

Def

ined

Dai

ly D

ose

s

2005 2006 2007Month and Year

Impact that Restricting Fluoroquinolones can Have on Reducing Unnecessary Antimicrobial Use

0

500

1000

1500

2000

2500

Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar

Aminoglycosides Cephalosporins (1st gen.)

Cephalosporins (2nd gen.) Cephalosporins (3rd and 4th gen.)

Quinolones Vancomycin

Piperacillin/Tazobactam Ampicillin/Sulbactam

Azithromycin Carbapenems

Aztreonam Clindamycin

Kallen, et al. 18th Annual Meeting of The Society for Healthcare Epidemiology of America (SHEA), April 6, 2008; Orlando, FL.

Desperate Measures for Desperate Times: Restricting all Fluoroquinolones to End an Outbreak

Kallen, et al. 18th Annual Meeting of The Society for Healthcare Epidemiology of America (SHEA), April 6, 2008; Orlando, FL.

0

5

10

15

20

25

Nu

mb

er o

f C

ases

Month and Year

Beginning of outbreak period

Quinolone restriction

New housekeeping company

Quinolone restriction partially lifted

2004 2005 2006 2007

• Hospitals should conduct surveillance for CDI – Track positive laboratory results– Consider measures to track outcomes

• Early diagnosis and treatment important for reducing severe outcomes and reducing transmission

• Strict infection control: CDC Fact Sheet* – Contact precautions for CDI patients– An environmental cleaning and disinfection strategy– Hand-washing with CDI patients in outbreak

• Antimicrobial management

Recommendations for Hospitals

*See CDC C. difficile Fact Sheets: http://www.cdc.gov/ncidod/dhqp/.

Human CDAD Caused by Strains Similar to Animal Epidemic Strains, 2001–2006Dice (Opt:1.10%) (Tol 1.1%-1.1%) (H>0.0% S>0.0%) [0.0%-100.0%]

100

9080706050

94.1

85.6

100

82.1

100

94.1

90.2

100

94.7

88.9

80.7

75.4

100

48.2

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

SourceBinary toxin

Toxinotype

tcdC deletion

Human

Human

Human

PigPigPig

Pig

Pig

PigPig

PigHumanHumanHumanHumanHosp Env

V

V

V

VVV

V

V

VV

VVVVVV

+

+

++

+

+

++++

+

++

+

+

+

+

39 bp

39 bp

39 bp39 bp

39 bp

39 bp

39 bp

39 bp39 bp39 bp

39 bp

39 bp39 bp

39 bp

39 bp

39 bp

39 bp

Jhung MA, et al. Second International Clostridium difficile Symposium, June 6-9, 2007; Maribor, Slovenia.

Summary

• Rates, mortality, and costs associated withCDI continue to increase

• Much of this increase may be due to emergence and spread of BI/NAP1/027

• Hospital rates can be controlled through tiered implementation of existing and enhanced recommendations

• Disease becoming more notable in previously low-risk populations

• Community-associated disease appears associated with variant toxinotypes

• Circumstantial evidence for animal-to-human transmission of toxinotype V strains