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Innovations in C. difficile Infection Diagnostics & Prevention

Explore the latest strategies in diagnosing and preventing Clostridioides difficile infection (CDI), including testing algorithms, primary and secondary prevention methods, and environmental cleaning solutions. Learn about current diagnostic tests and recommended strategies for managing CDI cases. Find out about the importance of antibiotic stewardship, contact isolation, and healthcare worker hand hygiene in preventing CDI. Discover how to implement enhanced room cleaning methods and the potential benefits of probiotics. Stay informed on the latest advancements in combating CDI outbreaks.

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Innovations in C. difficile Infection Diagnostics & Prevention

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  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-deesdif–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. 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 Moon PLoS ONE 2016

  9. Algorithm strategy • PCR as part of 2-step algorithm had significantly improved PPV: 93-100% 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 • 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 ClinMicrobiol 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 DubberkeClin 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 HiseClin 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 - NCT01670149

  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

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