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

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

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

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

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

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

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

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

Algorithm strategy PCR as part of 2-step algorithm had significantly improved PPV: 93-100% Caulfield Diagn Microbiol Infect Dis. 2018

Peng Emerg Microbes Infect. 2018

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

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

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

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

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

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

Environmental Cleaning Floors/surfaces RME

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

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

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

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”

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

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

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

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

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%

Pending RCT Studies Randomized OVP - NCT03200093, NCT03466502 Randomized to Rifaximin - NCT01670149

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