C. Diff Colitis Clostridium Difficile Update Transmission, Prevention, Treatment Maggie Hagan, M.D. History Described in 1935 by Hall and O Toole Named the Difficult Clostridium Found to colonize healthy newborns Found to be toxigenic 1978 C diff. Toxin found in the stool of patients with antibiotic associated diarrhea 1 2 Background: Impact Age-Adjusted Death Rate* for Enterocolitis Due to C. difficile, 1999 2006 Rate 2.5 2.0 1.5 1.0 0.5 Male Female White Black Entire US population Epidemiology of C diff Prevalence of asymptomatic colonization 7-50% of adult inpatients in acute care 5-7% among adults in long term care Risk of colonization increases during hospitalization 0 1999 2000 2001 2002 2003 2004 2005 2006 Year *Per 100,000 US standard population Heron et al. Natl Vital Stat Rep 2009;57(14). Available at http://www.cdc.gov/nchs/data/nvsr/nvsr57/nvsr57_14.pdf 3 4 1
Changing Epidemiology of C diff Estimated 500,000 cases of C diff/year in US Estimated 15,000-20,000 deaths/year Community C diff 7.6 cases/100,000 person years 35% have had no antibiotics within 42 days Changing Epidemiology of C diff Beginning in 2001 there was an abrupt increase in hospital discharges listing C diff as a diagnosis 5 fold increase in patients >65 Strain termed NAP1/BI/027 Increase in cases in healthy people/outpatients Nature. 2009:7;526-36 Critical Care 2008, 12:203 5 6 Pathogenesis of C diff A two hit phenomenon Colonization with C diff Alteration of gut flora with antibiotics Pathogenesis of C diff Oral ingestion of C diff spores Spores germinate into vegetative form in small intestine Disruption of commensal flora of intestine allows C diff to flourish C diff produces two exotoxins: Toxin A and Toxin B Critical Care 2008, 12:203 7 8 2
C diff Outbreaks Three Factors Implicated Increased production of Toxins A and B Floroquinolone resistance Production of a binary toxin Toxin Production in Epidemic Strains of C diff N Engl J Med. 2008: 359;18 9 N Engl J Med. 2008: 359;18 10 Pathogenesis of C diff Pathogenesis of C diff Nature. 2009:7;526-36 11 Nature. 2009:7;526-36 12 3
Risk Factors for C diff Advanced age Duration of hospitalization Exposure to antibiotics Chemotherapy HIV GI surgery Acid suppression 13 Clinical Manifestations of C diff Range from asymptomatic to fulminant disease Diarrhea Fever Abdominal pain Leukocytosis May have abdominal pain/distention without diarrhea in advanced disease 14 Clinical Manifestations of C diff Incubation period from acquisition of C diff to CDI is short (median2-3 days) Patients may remain at risk for C diff for 3 months or longer after they have stopped antibiotics MMWR Morb Mortal Wkly Rep 2012;61:157-162. 15 Diagnosis of C difficile Infection Testing should be performed only on diarrheal stool, unless ileus due to C diff is suspected Only a single specimen needed for testing PCR testing is rapid, sensitive and specific EIA testing for C diff toxin A and B is rapid but less sensitive Repeat testing during the same episode of diarrhea is discouraged No test of cure Infect Control Hosp Epidemiol 2010; 31,431-55. 16 4
Transmission of C diff Factors Associated with Increased Shedding of C diff Diarrhea Fecal incontinence High concentrations of organisms in the stool super shedders CID 2010:50:1458-61 17 18 Environment as a Source of Transmission of C difficile C diff is commonly isolated from the hands of health care providers The frequency of positive hand cultures is strongly correlated to the level of environmental contamination Hands 0% when Environment 0-25% Hands 8% when Environment 26-50% Hands 36% when Environment >50% Environment as a Source of Transmission of C difficile Acquisition of spores on gloved hands occurred as frequently after contact with environmental surfaces as after contact with skin sites (50% vs 50%) Prior room occupant with C diff is a significant risk factor for C diff acquisition (11% vs 5%) 1). Guerrero DM, et al. Am J Infect Control 2011 2). Shaughnessy MK, et al. Infect Control Hosp Epidemiol 2010;32:210-6 Am J Infect Control 2010;38:S25-33. 19 20 5
Environmental Sources of C difficile Electronic thermometers Blood pressure cuffs Bedside commodes Stethoscopes What Makes C diff Different From Other Bacteria? 21 22 Infection Control Measures for C diff Infection Gowns and gloves for contact with patients Wash hands with soap and water Private room or cohort patients with private commode Chlorine containing cleaning agents, terminal cleaning of rooms Antibiotic restraint 23 24 6
Special Approach to Prevent C diff Transmission Expedite identification and isolation of patients Prolong duration of contact precautions Improve bathing to reduce the burden of spores on skin Daily disinfection of high-touch surfaces during C diff treatment Use more sensitive diagnostic tests Cleaning of High Touch Surfaces Daily 25 26 Environmental Cleaning to Control C diff CDC, SHEA, IDSA all recommend use of a 1:10 dilution of sodium hypochlorite for environmental disinfection in outbreak settings of C diff Am J Infect Control 2010;38:S25-33. 27 28 7
29 30 UV Light and C diff Use of UV Light to Control C diff Numerous retrospective studies funded by industry Recent prospective study looking at environmental cultures 31 32 8
Use of UV Light to Control C diff Hand Hygiene for C diff C diff in its spore form is highly resistant to killing by alcohol Spores can be physically removed by soap and water Several studies have documented reduction in C diff rates by improvement in hand washing compliance Infect Control Hosp Epidemiol. May 2013; 34(5): 466 471. 33 Infect Control Hosp Epidemiol 2010;31:565 570. Infect Control Hosp Epidemiol. 2009 Oct;30(10):939-44. 34 C diff on Hands of HCWs Compared hand contamination 66 HCW caring for patients with CDI 44 HCW controls Monitored for 8 weeks Results C diff spores on 24% of samples of hands from HCWs caring for CDI patients No spores on hands of control HCWs Nursing assistants had highest rates Most of HCWs used gloves for patient contact Infect Cont and Hosp Epidemiol. January 2014;35 (1): 10-15 35 Summary of Prevention Measures Core Measures Contact Precautions for duration of illness Hand hygiene in compliance with CDC/WHO Cleaning and disinfection of equipment and environment Laboratory-based alert system CDI surveillance Education Supplemental Measures Prolonged duration of Contact Precautions* Presumptive isolation Evaluate and optimize testing Soap and water for HH upon exiting CDI room Universal glove use on units with high CDI rates* Bleach for environmental disinfection Antimicrobial stewardship program * Not included in CDC/HICPAC 2007 Guideline for Isolation Precautions 36 9
Measures to Improve C diff Rates Analyze rates Form a multidisciplinary performance improvement team Environmental cleaning Proper PPE Hand washing Antibiotic stewardship 37 38 Treatment of C diff Infection Metronidazole Vancomycin Fidaxomicin Probiotics Immunoglobulin Fecal Transplant 39 40 10
Treatment of C diff Infection Metronidazole vs Vancomycin Metronidazole is the drug of choice 500mg tid for 10-14 days Vancomycin drug of choice for severe infection 125-500mg qid for 10-14 days Tapering schedule for recurrent infections Severe/Complicated C diff Vancomycin 500mg po q 6 hours and Metronidazole 500mg IV q 8 hours Infection Control and Hospital Epidemiology, Vol. 31, No. 5 (May 2010), pp. 431-455 41 N Engl J Med. 2008: 359;18 42 Fidaxomicin vs Vancomycin Treatment of C diff Infection A multicenter, prospective, randomized, placebo controlled trial 629 patients enrolled at 52 sites No difference in cure rates Treatment with Fidaxomicin associated with lower rate of recurrence (15.4 vs 25.3%) Cost issues Vancomycin enema Fecal transplant Colectomy N Engl J Med 2011; 364:422-431 43 44 11
Fecal Transplantation Treating Clostridium difficile Infection With Fecal Microbiota Transplantation Obtain donor stool from a relative Screen donor for C diff Mix donor stool with tap water to make an solution Instill as an enema to the patient Via Christi has a protocol for FMT Requires specific consent form Clin Gastro and Hepatol., December 2011.9(12) 1044-1049 45 46 Probiotics in the Treatment of C diff Current C diff guidelines do not recommend use of probiotics Cochrane review 2008 reviewed 4 studies and found a statistically significant benefit in only one small study More recent studies of multi-strain probiotics show promise 47 48 12
Role of Immunotherapy in the Treatment of C diff Inability to mount an immune response appears to make patient susceptible to recurrent infections Favorable outcomes with use of IgG for recurrent infections No randomized controlled trials Vaccine for C diff is being studied 49 Nature. 2009:7;526-36 50 Immune Response to C diff Treatment of C diff Check IgG level on patients with severe or recurrent C diff Give a one-time dose of IVIG to patients with low IgG N Engl J Med. 2008: 359;18 51 52 13
Role of Antibiotic Stewardship in Controlling C diff Use of antibiotics is associated with increase in C diff rates Certain antibiotics are associated with higher C diff rates (floroquinolones) Several studies have shown reductions in C diff rates with effective antimicrobial management programs 53 14