1. What’s new in Clostridioides difficile infection diagnostics and prevention
March 9th, 2019
Brooke K. Decker, MD, CIC
Director, Antimicrobial Stewardship
Director, Infection Prevention
VA Pittsburgh Healthcare System

2. Learning objectives
Describe Clostridioides difficile diagnostics and guideline recommended testing strategy
Discuss C. diff prevention approaches

3. Talk outline Testing algorithm(s) Primary prevention
Secondary prevention
Clostridioides difficile
[klos–TRID–e–OY-dees dif–uh–SEEL]
Clostridioides difficile Infection (CDI)
500,000 cases/year in US
15,000 directly attributable deaths
CDC 2015

4. How to test for CDI Only test patients with symptoms
Unexplained, ≥3 diarrheal stools: Bristol scale 6 or 7 only -- “unformed”
+/- fever
Abdominal pain
Anorexia
Nausea
~7% pts colonized!
Bristol Stool Scale
Lewis & Heaton, Scand. J. Gastroenterol 1997
Galdys J Clin Microbiol 2014

5. CDI risk - intestinal dysbiosis
Antibiotic exposure (necessary or unnecessary)
fluoroquinolones, third/fourth generation cephalosporins, clindamycin, carbapenems
Gastrointestinal surgery/manipulation
Healthcare exposure
Immunocompromise
Advanced age
Proton pump inhibitors, H2-blockers
McDonald Clinical Infectious Diseases 2018

6. Available tests Enzyme immunoassay (EIA) for toxin
EIA for glutamate dehydrogenase (GDH)
Nucleic acid amplification (NAAT)
Algorithm recommended (EIA + NAAT or NAAT + EIA?)
McDonald Clinical Infectious Diseases 2018

7. A patient presenting with positive NAT testing for C
A patient presenting with positive NAT testing for C. difficile should prompt:
Immediate guideline-concordant rx for CDI
Immediate contact isolation
Re-evaluation of hospital testing strategy
A phone call to your Antimicrobial Stewardship coordinator
Further clinical investigation

8. Test comparison Test Sensitivity Specificity PPV NPV EIA Toxin 49.1%
98.2%
87.1%
88.3%
EIA GDH
96.4%
85.2%
62.4%
NAAT
94.6%
94.9%
82.5%
98.6%
GDH + PCR
96.7%
95.8%
85%
98.1%
GDH + Toxin + NAAT
94.5%
82.3%
98.5%
Moon PLoS ONE 2016

9. Algorithm strategy
PCR as part of 2-step algorithm had significantly improved PPV: %
Caulfield Diagn Microbiol Infect Dis. 2018

10. Peng Emerg Microbes Infect. 2018

11. Alternative to 2-step: Stool QC
Educate clinicians to only send stool on patients with symptoms and clinical picture consistent with CDI and no recent use of laxative
Empower laboratory personnel to reject non-liquid specimens
This may be as effective in improving PPV as a multistep algorithm
McDonald Clinical Infectious Diseases 2018

12. Algorithm strategy Toxin EIA is not sensitive (false negative)
NAAT is very sensitive (false positive)
First-step NAAT + confirmatory toxin EIA
Sensitivity + potential reduction in unnecessarily reported cases
NAAT+/Tox- cases may be heterogenous regarding infected status
Your CEO wants a 2-step NAAT-EIA strategy (reduced reporting of HO-CDI)
Planche Lancet Infect Dis 2013
Zou Eur J Clin Microbiol Infect Dis. 2018

13. Primary Prevention Antibiotic Stewardship Contact isolation
Baur Lancet Infect Dis 2017
Contact isolation
Environmental Cleaning
Healthcare worker hand hygiene
Universal Screening?
Probiotics?

14. Contact isolation Private, single room, dedicated toilet
Gloves and gowns for HCW
Isolate pending results of testing
Isolation duration??
At least 48 hours
5 days?
Hospitalization duration?
McDonald Clinical Infectious Diseases 2018

15. Potentially infectious C. difficile may remain in the environment for:
1-2 days
1-2 weeks
1-2 months
Until the next bleach clean/UV light cycle

16. Sites were cleaned daily and after each collection (continued shedding)
Sethi Infect Control Hosp Epidemiol. 2010

17. Environmental Cleaning
Floors/surfaces
RME

18. Floors Historically controversial in CDI cleaning
Spore-active cleaners hard on flooring
It’s probably a real risk

19. Solutions Enhanced room cleaning methodology (targeted vs. universal)
Hydrogen peroxide
Periodic bleach cleaning
UV light disinfection
Marra Infect Control Hosp Epidemiol 2018
Anderson Lancet 2017
Anderson Lancet Infect Dis 2018

20. Environmental Cleaning - RME
Reusable medical equipment (RME)
It’s everything
Who cleans it
What do they clean it with
How often

21. Solutions Find out who cleans RME
Prepare for the answer to be no one
Ensure RME cleaning is assigned, trained, and validated
Consider a universal periodic bleach clean day – “Bleach clean Friday”

22. Universal Screening Melzer – 3.4% hospital admissions positive by PCR
HO-CDI 4.6/10k for non-colonized pts
HO-CDI 76.6/10k for colonized pts
Longtin – 4.8% positive on admission, all isolated on detection.
HO-CDI 6.9/10k pre-intervention
HO-CDI 3/10k during intervention
Melzer Clin Microbiol Infect. 2019
Longtin JAMA Intern Med. 2016

23. Probiotics or no biotics
Lactobacilli and bifidobacterial (PLACIDE) study
No evidence of prevention of antibiotic or C. diff associated diarrhea
RBX2660 (suspension of donor stool administered by enema)
2 doses superior to placebo in RCT, 1 dose not superior over placebo
Allen Lancet. 2013
Dubberke Clin Infect Dis. 2018

24. Secondary Prevention
Your patient with a history of CDI needs broad-spectrum antibiotics again!

25. Oral Vancomycin Prophylaxis (OVP)
Retrospective study -- history of CDI treated with OVP (vanc 250 bid, 125 bid)
OVP group recurrence 4.2%
Control group 26.6%
Long term treatment with 125 mg OVP may be effective in preventing relapse
OVP 125 mg po daily or bid effective 2ndary PPX
Oral vanc 125 mg po bid for allo-SCT pts – 0% CDI in ppx’d, 20% in non-ppx’d group
Van Hise Clin Infect Dis. 2016
Zhang BMC Infect Dis 2019
Brown Ann Pharmacother 2019
Ganetsky Clin Infect Dis. 2018

26. Fidaxomcyin vs. placebo: DEFLECT-1
CDI (primary) prevention for Allo-SCT
CDI from start of study to 30 days post-treatment similar:
Treated: 28.6%
Placebo: 30.8%

27. Pending RCT Studies Randomized OVP - NCT03200093, NCT03466502
Randomized to Rifaximin - NCT

28. News you can use:
Know how your lab is testing (and add your grains of salt as needed)
Wash your hands and bleach your stethoscope (and other RME)
Stay tuned for much-needed additional research on secondary prophylaxis