Clostridium difficile infection: The Present and the Future Carlos E. Figueroa Castro, MD Assistant Professor, Division of Infectious Diseases Medical College of Wisconsin November 2014
I have made this presentation longer than usual, because I lack the time to make it short. Inspired by Blaise Pascal
Faculty Disclosure Nothing to disclose
Objectives Briefly review the latest SHEA/IDSA C.difficile infection (CDI) management guideline Review treatments in active development against CDI Speculate about the treatment of CDI in the next fifty years
Why talking about C.difficile? Leading cause of hospital-acquired infections Increased morbidity and mortality Increase in length of stay and care costs Emerging infection in the community setting
Rates of US short-stay hospital discharges with Clostridium difficile listed as any diagnosis, by age McDonald LC, Owings M, Jernigan DB. Emerg Infect Dis. 2006;12(3):409-15
Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe Warny M et al. Lancet 2005;366:1079 84
DOI: 10.1086/651706.http://www.jstor.org/stable/10.1086/651706
General Principles: Testing Do Test in unformed stool only Do not Repeat test during treatment Test asymptomatic patients Obtain test after treatment
General Principles: Infection Control Contact isolation for everyone Hand hygiene with soap and water Private room or cohorting Clean with bleach or sporicidal agents
General Principles: Treatment Minimize antibiotic use Antimicrobial stewardship program Clinical presentation guides choice of treatment Avoid prolonged metronidazole use Do not use cholestyramine
Treatment of C.difficile infection Severity of Infection Treatment Mild to Moderate Severe Severe, complicated Metronidazole 500mg po three times a day for 14 days Oral vancomycin 125mg po four times a day for 14 days Oral vancomycin plus IV metronidazole Vancomycin retention enema Surgical evaluation
Acquisition of toxigenic C.difficile in the community Stop unnecessary antimicrobial use Barrier precautions Environmental cleaning Vaccines Monoclonal antibodies Gerding DN, Johnson S. Clin Infect Dis. 2010;51(11):1306-13
Treatment Options for C.difficile Infection Approved by FDA Off-label Use New Drugs Biotherapeutics Vancomycin Metronidazole Fidaxomicin Rifaximin Nitazoxanide Tigecycline LFF571 (Novartis) Surotomycin (CB-183, 315, Cubist) SMT 19969 (Summit) Cadazolid (ACT-179811, Actelion) Oritavancin (LY333328, The Medicines Company) Cholate meta-benzene sulfonic derivative (CamSA) Fecal microbiota transplantation VP 20621 (Viropharma) Probiotics IVIG Monoclonal antibodies Vaccines
Rates of Cure without Relapse for Recurrent Clostridium difficile Infection Interventions: Vancomycin, bowel lavage, donor feces Vancomycin, bowel lavage Vancomycin Primary end point: Resolution of diarrhea without relapse after 10 weeks van Nood E et al. N Engl J Med 2013;368:407-415
http://www.npr.org/blogs/health/2014/10/11/355126926/frozen-poop-pills-fight-life-threatening-infections
Oral, Capsulized, Frozen Fecal Microbiota Transplantation for Relapsing Clostridium difficile Infection Twenty patients (median: 64.5 years; range: 11-89) At least 3 episodes of mild to moderate C.difficile infection or 2 episodes of severe infection 15 capsules in 2 consecutive days Open-label,single-group,preliminary feasibility study Youngster I, JAMA [Internet]. 2014; Available from: + http://dx.doi.org/10.1001/jama.2014.13875
Oral, Capsulized, Frozen Fecal Microbiota Transplantation for Relapsing Clostridium difficile Infection Results: No adverse effects Decline in bowel movements Better self-ranked health scores Patient requiring retreatment had a lower pre-treatment health score Youngster I, JAMA [Internet]. 2014; Available from: + http://dx.doi.org/10.1001/jama.2014.13875
http://www.wired.com/2011/09/mf_microbiome/
http://www.genome.gov/sequencingcosts/
Wired s Guide to Crafting the Perfect TED talk http://www.wired.com/2013/04/tedtalk/
Conclusions C.difficile infection is an important pathogen in both the hospital and the community Use the SHEA/IDSA guideline as a starting point to improve quality of care Future advances are linked to a deeper understanding of the human gut microbiome