Overview of C. difficile infections. Kurt B. Stevenson, MD MPH Professor Division of Infectious Diseases

Overview of C. difficile infections Kurt B. Stevenson, MD MPH Professor Division of Infectious Diseases

Conflicts of Interest I have no financial conflicts of interest related to this topic and presentation. I have research funding from the National Institutes of Health 2

Objectives Review the microbiology of Clostridium difficile Outline epidemiology of C. difficile transmission and infection Discuss the infection prevention and antimicrobial measures to decrease C. difficile infection rates Review treatment strategies for C. difficile infection 3

Microbiology Gram-positive spore-forming anaerobic bacteria Found in water, air, and human/animal feces Spores allow it to persist in the environment under harsh conditions It can grow to high concentrations in the human gut in the presence of antibiotics It produces two toxins, A and B. Toxin B interacts with mast cells to produce inflammation and Toxin A releases prostaglandins resulting in diarrhea, inflammation, fever, and abdominal pain 4

McDonald, LC et al. New Engl J Med 2005;353:2433-41

Epidemiology Present in the environment (soil, hospital environment) Hospitals are the major reservoir 3% of healthy adults colonized 20-40% of hospitalized patients colonized Spread on the hands of HCWs Transmitted by the fecal oral route CD spores have been recovered from: Hospital toilets Thermometers Metal bedpans Floors Commodes 6

Epidemiology Antibiotic exposure is the single most important risk factor for the development of Clostridium difficile infection (CDI). Up to 85% of patients with CDI have antibiotic exposure in the 28 days before infection Chang HT et al. Infect Control Hosp Epidemiol 2007; 28:926 931 7

Antibiotic Use and CDI More Frequent Later generation cephalosporins Ampicillin/amoxicillin Clindamycin Other penicillins Macrolides Tetracyclines TMP-SMX Bartlett JG N Engl J Med 2002;346:334 Kelly CP et al. N Engl J Med 1994;330:257 Dial S JAMA 2005;294:2989-2995 Less Frequent Ticarcillin-clavulanate Metronidazole Fluoroquinolones Rifampicin 5-Flurouracil Cyclophosphamide doxorubicin Methotrexate NSAIDS Proton-pump inhibitors 8

Increased fluroquinolone use The recent introduction of fluoroquinolones with spectrum of activity against agents of community-acquired pneumonia and respiratory pathogens has dramatically increased their utilization Linder JA et al Am J Med 2005;118:259-268 10

Rising incidence of CDI Data collected from the National Hospital Discharge Survey have been used to assess the increase in CDAD over time From 1996 to 2003, there were an estimated 264,000 and 978,000 discharges for which C. difficile was either the primary or any diagnosis First diagnosis 25,000 (2000), 54,000 (2003) (p<0.001) McDonald LG et al. Emerg Infect Dis 2006;12 (3) Epub ahead of print 11

McDonald LG et al. Emerg Infect Dis 2006;12 (3)

Evidence for CDI-pressure in Hospitals CDI pressure =1 days in unit CDI pressure =5 days in unit Unit A Few patients with active CDI = lower risk of acquiring CDI Unit B More patients with active CDI = higher risk of acquiring CDI Dubberke ER, et al. Clin Infect Dis. 2007;45:1543-1549.

Clinical symptoms Onset of fever, diarrhea with frequent watery foulsmelling stools, leukocytosis, abdominal pain Severe CDI: WBC>15,000, serum albumin <3, elevated serum creatinine Can be complicated by development of toxic megacolon with sever sepsis requiring colectomy in most severe cases 16

Emergence of hypervirulent outbreak strain Emergence of the NAP-1/BI or epidemic strain of C. difficile has intensified the risks associated with antibiotic exposure. Epidemic strain is resistant to fluoroquinolone antibiotics, which confers a selective advantage. 17

CDI Outbreaks Quebec hospitals University of Pittsburgh Increasing reports in the USA and worldwide 18

Muto CA, et al. ICHE 26:273-290

U Pittsburgh Outbreak Multivariable analysis Ceftriaxone OR 5.4 (1.8 to 15.8) 21 cases Clindamycin OR 4.8 (1.9-12.0) 32 cases Levofloxacin OR 2.0 (1.2-3.3) 120 cases Other significant factors: diabetes, transplant, H2 blockers, proton pump inhibitors Muto CA, et al. ICHE 26:273-290 22

Loo VG, et al. New Engl J Med 2005;353:2442-2449

Variant Epidemic Strains (BI/NAP1) Restriction enzyme analysis (REA) typing=bi PFGE typing=nap1 PCR-Ribotyping=027 Toxinotyping=Type III Increased production of Toxins A and B Produces binary toxin Resistant to fluoroquinolones Exposure to fluoroquinolones and cephalosporins is a risk factor 26

McDonald, LC et al. New Engl J Med 2005;353:2433-41

Warny M, et al. Lancet 2005;366:1079-1084

Mechanisms of Control Prevent cross transmission using infection prevention methods Prevent development of colitis by optimizing antimicrobial use 32

Conclusions 3.6 year study; Oxfordshire, United Kingdom 1200 patients Only 35% of cases were genetically related to at least one previous case. These data show that in a majority of cases, C. difficile infection is not transmitted from another previous symptomatic patient 34

35 Infect Control Hosp Epidemiol 2014;35:628

Recommendations for CDI Prevention Encourage appropriate use of antimicrobials Lab based alert system for immediate notification Conduct CDI surveillance for hospital-onset cases Ensure cleaning and disinfection of the environment Daily bleaching and terminal cleaning Use (Enteric)Contact Precautions for infected pts, single pt room preferred especially if incontinent HH, gloves and gowns Dedicated patient care equipment and CLEAN immediately after use ICHE June 2014

Recommendations for CDI Prevention Educate HCP, EVS and administration Educate patients and families about CDI Measure compliance with CDC HH and Enteric Contact precautions ICHE June 2014 39

Special approaches to Prevent CDI Goal to higher HH compliance (93%) During outbreaks, use soap and water upon exit Place suspect CDI pts in contact precautions Prolong duration of precautions after pt becomes asymptomatic until discharge (III) Assess adequacy of room cleaning (III) Use a sporocidal disinfectant Initiate an ASP: PPI restriction, probiotics? 40 ICHE June 2014

Impact of antimicrobial optimization Tertiary care hospital; Quebec, 2003-2006 Valiquette, et al. Clin Infect Dis 2007;45:S112 41

Antimicrobial Stewardship Antimicrobial stewardship includes not only limiting inappropriate use but also optimizing antimicrobial selection, dosing, route, and duration of therapy to maximize clinical cure or prevention of infection while limiting the unintended consequences, such as the emergence of resistance, adverse drug events, and cost. Clin Infect Dis 2007;44:159-177

Clin Infect Dis 2007; 44:159 77

Evidence-Based Practices Active Strategies Prospective audit with intervention and feedback Formulary restriction and preauthorization Supplemental Strategies Education Guidelines and clinical pathways Antimicrobial cycling Antimicrobial order forms Streamlining or de-escalation of therapy Dose optimization Parenteral to oral conversion Clin Infect Dis 2007; 44:159 77

Components of Antimicrobial Management Front End provided at the point of prescribing Formulary Restriction and Preauthorization Interactive decision support Guidelines, order sets Requires additional IT support and personnel (e.g. pharmacists) Back End after the antimicrobial has been prescribed Prospective Feedback Audit Streamlining or de-escalation Dose optimization Parenteral to oral conversion Requires additional personnel support (e.g. pharmacists)

46 CDC initiative

Antibiotic Time Out Step 1: Build dose, duration, indication into the computer based antibiotic order Step 2: Reflex antibiotic order to require microbiological cultures to be ordered Step 3: Take an Antibiotic Time Out: series of questions the team discusses for each patient on antibiotics 47

48 Treatment

Treatment Metronidazole Oral vancomycin Fidaxomicin Fecal microbiota transplant Colectomy 49

Questions??? kurt.stevenson@osumc.edu 614-293-5666 53