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Gastrointestinal Clostridium Difficile (Pseudomembranous Colitis): Evidence‐Based Approach to Clostridium Difficile Colitis (CME098‐099) Hemorrhoids and Anal Fissure: Anorectal Disease ‐ Diagnosis and Treatment (CME100‐ 101) Hernia (Abdominal) (CME102‐103) Liver Function Tests: Is Something Wrong With My Liver? (CME104‐105) Probiotics and the GI Tract, What Should A Busy Clinician Know (CME106‐107) Handouts as of 9/17/18 Clostridium Difficile (Pseudomembranous Colitis): Evidence-Based Approach to Clostridium Difficile Colitis Joel Heidelbaugh, MD, FAAFP ACTIVITY DISCLAIMER The material presented here is being made available by the American Academy of Family Physicians for educational purposes only. Please note that medical information is constantly changing; the information contained in this activity was accurate at the time of publication. This material is not intended to represent the only, nor necessarily best, methods or procedures appropriate for the medical situations discussed. Rather, it is intended to present an approach, view, statement, or opinion of the faculty, which may be helpful to others who face similar situations. The AAFP disclaims any and all liability for injury or other damages resulting to any individual using this material and for all claims that might arise out of the use of the techniques demonstrated therein by such individuals, whether these claims shall be asserted by a physician or any other person. Physicians may care to check specific details such as drug doses and contraindications, etc., in standard sources prior to clinical application. This material might contain recommendations/guidelines developed by other organizations. Please note that although these guidelines might be included, this does not necessarily imply the endorsement by the AAFP. This CME session is supported by an educational grant from Merck. 1 DISCLOSURE It is the policy of the AAFP that all individuals in a position to control content disclose any relationships with commercial interests upon nomination/invitation of participation. Disclosure documents are reviewed for potential conflict of interest (COI), and if identified, conflicts are resolved prior to confirmation of participation. Only those participants who had no conflict of interest or who agreed to an identified resolution process prior to their participation were involved in this CME activity. All individuals in a position to control content for this session have indicated they have no relevant financial relationships to disclose. The content of my material/presentation in this CME activity will include discussion of unapproved or investigational uses of products or devices as indicated: • Will discuss the use of fecal microbiota transplantation. Joel Heidelbaugh, MD, FAAFP Clinical Professor, Departments of Family Medicine and Urology/Director of Medical Student Education and Clerkship Director, Department of Family Medicine/Director, Patients and Populations Branch, University of Michigan Medical School, Ann Arbor Dr. Heidelbaugh is a family physician who has 19 years of academic teaching experience. His specialty topics include gastrointestinal disorders, men's health, and primary care urology. He is a member of the American Gastroenterological Association guideline panels for irritable bowel syndrome, inflammatory bowel disease, and Lynch syndrome. He is the co-editor and co-author of the textbook ROME IV: Functional Gastrointestinal Disorders for Primary Care and Non-GI Clinicians, published through the Rome Foundation. In addition, he is the consulting editor of Primary Care: Clinics in Office Practice and the president-elect of the American Society for Men's Health. Dr. Heidelbaugh believes that increasing awareness and education about gastrointestinal and men's health issues is an important trend in medical education, clinical practice, and research. 2 Learning Objectives 1. Discuss implementation measures for the clostridium difficile prevention. 2. Review the serologic and radiologic diagnostic criteria for clostridium difficile infection. 3. Identify treatment approaches for clostridium difficile based on severity. 4. Review the usage of supplements and medications associated with the development and prevention of clostridium difficile infections. Audience Engagement System Step 1 Step 2 Step 3 3 Public Health Problem • Most commonly recognized cause of infectious diarrhea in healthcare settings • PCR ribotype 027 / North American pulsed field type 1 (NAP1) most prevalent • Pooled rate healthcare facility onset (HO) - Clostridium difficile infection (CDI) • 7.4 per 10,000 patient-days • US (2011) - estimated number of incident CDI cases • 453,000 or 147 cases/100,000 persons • 293,000 were directly healthcare-associated • Severity of CDI is highly variable • based upon lab data, physical exam findings, ICU stay duration, presence or absence of colectomy • mortality with colectomy rates ranges from 0.3 - 1.3% Infectious Disease Society of America Clinical Practice Guidelines CID 2018:66 (1 April) AES Question # 1 Which of the following is a major risk factor for the development of Clostridium difficile infection? A. A high fat diet B. Decreased serum creatinine C. Decreased serum albumin D. Decrease serum chloride E. A high carbohydrate diet 4 Risk Factors • Advanced age (> 65 years of age), women, white race • Duration of hospitalization • Antibiotics - even a single exposure increases risk • Penicillins, 3rd and 4th generation Cephalosporins • Fluoroquinolones • Carbapenems • Clindamycin • Cancer chemotherapy / immunosuppression / corticosteroids • Risk factors associated with complicated diseases • Human immunodeficiency virus (HIV) • Hypoalbuminemia • Leukocytosis • Renal failure Infectious Disease Society of America Clinical Practice Guidelines CID 2018:66 (1 April) Epidemiology • Most likely to result from person-to-person spread through fecal-oral route or direct exposure to a contaminated environment • Prevalence of symptomatic colonization with CD is 3 - 26% among adult inpatients in acute care hospitals • Prevalence of CD in stool in asymptomatic adults without recent healthcare facility exposure is < 2% • Meta-analysis found that pooled colonization rate upon hospital admission across 19 studies between 2005-2014 was 8.1% with main risk factor being previous hospitalization • Routes of transmission - hands of healthcare workers and contaminated environment occupying room of patient with CDI - 10% Infectious Disease Society of America Clinical Practice Guidelines CID 2018:66 (1 April) 5 Burden of Illness Lessa FC, et al. N Engl J Med 2015; 372:825-834. Clostridium difficile Pathophysiology • Spore forming bacterium • Forms hard defensive shell (dies if pH < ~4) • Lies in a dormant state for long periods of time • Do not directly cause a concerning infection !!! • Can easily revert back to the active form of the bacterium and lead to C. Difficile treatment.com - Accessed at:https://www.c-difficile-treatment.com/faq/ infection if ingested 6 Bagdasarian N, et al. JAMA 2015;313(4):398-408. 7 Furuya-Kanamori, et al. BMC Infectious Diseases2015;15:516 AES Question # 2 Which of the following medication classes is associated with a higher risk of Clostridium difficile infection? A. Alpha blockers B. Beta blockers C. HMG Co-A reductase inhibitors D. Centrally-acting muscle relaxants E. Non-steroidal anti-inflammatory drugs 8 Medications Implicated in CDI • Anti-Secretory Therapy • Histamine-2 receptor antagonists (H2RAs) • Proton pump inhibitors (PPIs) • Antidepressants • Serotonin-specific reuptake inhibitors (SSRIs) • Whatever CLASS mirtazapine is ….. • Anti-inflammatories • Non-steroidal anti-inflammatory drugs (NSAIDs) Anti-Secretory Therapy • Systematic review and meta-analysis of 42 observational studies with over 313,000 patients • Studies had to report odds ratios/relative risk of development of CDI or have present comparative data • Pooled odds ratios • H2RA alone - 1.50 (95% CI - 1.23-1.83) • Antibiotics alone - 1.97 (95% CI 1.29-3.01) • PPI alone - 2.10 (95% CI - 1.66-2.66) • PPI + antibiotic - 3.87 (95% CI 2.28-6.56) Kwok CS, et al. Am J Gastroenterol. 2012;107(7):1011-1019. 9 Anti-Secretory Therapy • Retrospective cohort study to determine impact of continuous PPI use on CDI recurrence of patients with hospital-acquired CDI • 754 patients - 458 PPI users / 296 PPI non-users • 101 patients had no indication for PPI use • Adjusted relapse rates of CDI • Age > 75 years - 1.5 (95% CI 1.1-2.0) • Continuous PPI use - 1.5 (95% CI 1.1-2.0) • Antibiotic re-exposure - 1.3 (95% CI 0.9-1.7) • Length of stay, per day - 1.003 (95% CI 1.002-1.004) McDonald EG et al., JAMA Intern Med 2015;175(5):784-791. Anti-Depressants • Combination of 2 studies • Study 1: Health and Retirement Study • Interview data linked to CMS records • Relationship between depression and CDI rates • Study 2: Hospital Based Case control study • Patients with stool + CDI compared to - CDI • Medication exposures • Depression linked to changes in gut microbiota Rogers MAM, et al. BMC Medicine 2013;11:121. 10 Anti-Depressants Rogers MAM, et al. BMC Medicine 2013;11:121. Anti-Inflammatories • Population based case-control study • CDI in UK GP database 1994-2005 • 1360 cases with 13,072 controls • Each CDI case matched with ~ 10 controls • Primary analysis: odds ration for CDI with NSAID use Suissa D, et al. Br J ClinPharmacol. 2012 Aug;74(2):370-375. 11 Anti-Inflammatories Suissa D, et al. Br J ClinPharmacol. 2012 Aug;74(2):370-375. Anti-Inflammatories Suissa D, et al. Br J ClinPharmacol.