1. Clostridium Difficile: Epidemiology and Clinical Spectrum Cassandra D Salgado, MD, MS Associate Professor of Medicine Hospital Epidemiologist, MUSC March 15, 2012

2. I have no Disclosures to report relevant to the content of this presentation. Cassandra D Salgado, MD, MS Associate Professor of Medicine Hospital Epidemiologist, MUSC March 15, 2012

3. Case Presentation 50 year old female was admitted for COPD exacerbation. She was treated with steroids, inhalers, and antibiotics. On hospital day 6 she develops fever of 102°F hypotension, diarrhea, and increased WBC count with profound bandemia (WBC= 48,000 with 30% bands). Septic workup was done…

4. Case Presentation Patient continued to decompensate with continued fevers and hypotension requiring vasopressors and transfer to MICUPatient continued to decompensate with continued fevers and hypotension requiring vasopressors and transfer to MICU Bowel movements ceased on hospital day 8 and patient was evaluated for toxic megacolon…Bowel movements ceased on hospital day 8 and patient was evaluated for toxic megacolon…

5. Case Presentation: X-ray Profoundly dilated bowel with wall thickening

6. Case Presentation The patient was taken to surgery…The patient was taken to surgery…

7. Case Presentation Colectomy was performedColectomy was performed Patient died on hospital day 9: autopsy revealed severe disease and pseudomembranous colitisPatient died on hospital day 9: autopsy revealed severe disease and pseudomembranous colitis

8. Clostridium difficile (C. diff) C. diff is a spore forming gram-positive anaerobic bacillus that produces at least two exotoxins (A and B) and a binary toxinC. diff is a spore forming gram-positive anaerobic bacillus that produces at least two exotoxins (A and B) and a binary toxin The ability to produce spores allows C. diff to be acquired from outside the hostThe ability to produce spores allows C. diff to be acquired from outside the host

9. C. difficile: Epidemiology “difficult” to isolate in laboratory“difficult” to isolate in laboratory 1978: cause of pseudomembranous colitis1978: cause of pseudomembranous colitis Most commonly recognized microbial cause of hospital-acquired diarrheaMost commonly recognized microbial cause of hospital-acquired diarrhea 3-5% of healthy adults are colonized3-5% of healthy adults are colonized 20-40% of hospitalized patients are colonized20-40% of hospitalized patients are colonized Asymptomatic carriers outnumber patients with disease by several foldAsymptomatic carriers outnumber patients with disease by several fold Bartlett JG. NEJM 1978;298:531. Viscidi R. Gastroenterol 1981;81:5. McFarland LV. NEJM 1989;320:204.

10. Clostridium Difficile: Risk Factors Exposure to antibiotics the preeminent risk factor for developing diseaseExposure to antibiotics the preeminent risk factor for developing disease More than 90% of healthcare-associated CDI occur while on antibioticsMore than 90% of healthcare-associated CDI occur while on antibiotics –Agents active against anaerobic organisms are considered to present the greatest risk (clindamycin) –Most cases are associated with β-lactam therapy –Growing number of reports of associations with fluoroquinolone therapy –Duration of antecedent therapy may be brief (surgical prophylaxis)

11. C. Diff and Antibiotic Use Broad-spectrum agents with a greater effect on the normal intestinal flora have been associated with CDADBroad-spectrum agents with a greater effect on the normal intestinal flora have been associated with CDAD Meta-analysis: 49 studiesMeta-analysis: 49 studies Bignardi GE. J Hops Infect 1998;40:1. Pooled Odds Ratio 95%CI Penicillin2.01.1-4.5 1st Gen Ceph 2.61.8-3.7 Quinolones8.04.5-14.3 Clindamycin9.06.3-12.9 Antipseudo PCN 9.64.2-21.8 Cefoxitin10.63.0-37.5 Ceftazadime28.812.7-65.1 Cefotaxime36.219.0-68.9

12. Clostridium Difficile: Risk Factors Cancer with or without chemotherapyCancer with or without chemotherapy GI surgery and other types of GI manipulationGI surgery and other types of GI manipulation Older ageOlder age Severity of illnessSeverity of illness Immunocompromising conditionsImmunocompromising conditions Longer duration of stay in hospitalLonger duration of stay in hospital ICU stayICU stay Exposure to an infected roommateExposure to an infected roommate Anti-ulcer medicationsAnti-ulcer medications Bignardi GE. J Hops Infect 1998;40:1.

13. C. diff: Special Populations Most cases of CDI occur in healthcareMost cases of CDI occur in healthcare Among hospitalized patientsAmong hospitalized patients –Medical patients are at increased risk compared to surgical patients C. diff is the most common cause of acute diarrheal illness in LTCFC. diff is the most common cause of acute diarrheal illness in LTCF –Population is older, receive more medications known to increase risk of C. diff Neonates may also be colonized with C. diffNeonates may also be colonized with C. diff –Up to 70% –Neonates colonized with toxogenic strains less likely than adults to develop symptomatic disease Neonates may lack receptors for toxin A in their immature enterocytesNeonates may lack receptors for toxin A in their immature enterocytes Sunenshine R. Clev Clinic J Med 2006;73:187.

14. Clostridium difficile: Clinical Disease Can cause diarrhea, severe GI disease, and sometimes death Antibiotic therapy Disruption of colonic microflora C. Diff exposure (fecal-oral) and colonization Release of toxin A (enterotoxin) and toxin B (cytotoxin) Mucosal injury and inflammation…

15. Clostridium difficile: Clinical Disease Watery diarrhea (10-15 times per day) Lower abdominal cramping Low grade fever Leukocytosis (WBC>15,000) Symptoms generally occur during antibiotic therapy Sometimes 5-10 days after completion Rarely weeks after completion Physical exam: abdominal tenderness

16. CDI vs. AAD

17. C. diff: Clinical Disease Effect of Toxin

18. C. diff: Clinical Disease Pseudomembranous colitis: toxin induced shallow ulcerations which release proteins, mucus, and inflammatory cells Type 1- mildest changes confined to superficial layers Type 2- more severe with marked secretions Type 3- intense necrosis and full intestinal thickness involvement produces a confluent membrane

19. C. diff: Clinical Disease Fulminant colitis (rare) Severe abdominal pain, abdominal distention, diarrhea, fever, hypovolemia, lactic acidosis. Marked leukocytosis (WBC>40,000) Toxic Megacolon (rare) Severe abdominal pain, abdominal distention, scant to no diarrhea, fever, shock, marked leokocytosis

20. Clostridium difficile: Clinical Disease X-ray: distended bowel and colonic wall thickeningX-ray: distended bowel and colonic wall thickening CT scan: colonic wall thickening and/or pericolonic strandingCT scan: colonic wall thickening and/or pericolonic stranding

24. Clostridium Difficile: At What Cost? Estimated 3,000,000 new cases of C. diff diarrhea and colitis in US hospitals annuallyEstimated 3,000,000 new cases of C. diff diarrhea and colitis in US hospitals annually –Affects as many as 10% of patients hospitalized for more than 2 days –Relapsing disease occurs in 20-25% of adequately treated patients Further relapses occur in 65% of patients who have suffered more than one relapseFurther relapses occur in 65% of patients who have suffered more than one relapse

25. Clostridium Difficile: At What Cost? StudyMortalityLOS (excess)Costs Miller MA. 2002 1.5%13.6 days$85,000 per yr Kyne L. 2002 NR10.2 (3.6) days$3,669 per pt McFarland LV. 1999 0%NR$10,970 per pt Wilcox MH. 1996 NR46.5 (21.3) days£4,000 per pt Riley TV. 1995 NR24.5 (18) days*$1,250,000 per yr Macgowan A. 1995 NR49.8 (30.2) daysNR Olson MM. 1994 0.6%NR Kofsky P. 1991 NR $2,000 to $5,000 per pt *Australian dollars

26. Clostridium DifficileClostridium Difficile –Spore forming toxin producing bacillus responsible for most nosocomial diarrhea. Risks for CDI include antibiotic exposure, other drugs, older age, and co-morbidities. CDI has been associated with notable morbidity, but traditionally low rates of severe disease and mortality.

27. C. diff: New Epidemiologic Issues C. diff rates are increasingC. diff rates are increasing More severe disease with higher mortality and higher rates of colectomyMore severe disease with higher mortality and higher rates of colectomy A common epidemic strain has been found in North America and EuropeA common epidemic strain has been found in North America and Europe –Fluoroquinolone use may be driving its emergence

28. CDI is Increasing Average rate of CDI among NNIS hospitals from 1987-1998Average rate of CDI among NNIS hospitals from 1987-1998 –12.2 cases per 10,000 pt-days Teaching hospitals: 13.0 per 10,000 pt daysTeaching hospitals: 13.0 per 10,000 pt days Non-teaching hospitals: 11.4 per 10,000 pt daysNon-teaching hospitals: 11.4 per 10,000 pt days CDC reports that hospitalizations with a discharge diagnosis of CDICDC reports that hospitalizations with a discharge diagnosis of CDI –Was 31 per 100,000 in 1996 –Was 61 per 100,000 in 2003 www.CDC.gov

29. CDI is Increasing

31. C. diff-Associated Infection Incidence of CDI per 10,000 patient days NNIS 1987-2001 Archibald et al JID 2004;189:1585 Recent data: Incidence of healthcare-associated C. diff colonization and infection are 29.5 and 28.1 cases per 10,000 pt days, respectively.

32. C. diff: Increased Morbidity and Mortality A hospital in Pittsburgh reports 253 nosocomial CDI cases in 2 years with an increase from 2.7 to 6.8 cases per 1,000 discharges (p<0.001) 1A hospital in Pittsburgh reports 253 nosocomial CDI cases in 2 years with an increase from 2.7 to 6.8 cases per 1,000 discharges (p<0.001) 1 –26 (10%) colectomies –18 (7%) mortality A Chicago hospital reports increased severity of CDI and increased mortality in MICU and oncology patients 2A Chicago hospital reports increased severity of CDI and increased mortality in MICU and oncology patients 2 –high rates of shock –37% mortality 1 Muto et al. ICHE 2005;26:273., 2 Patel et al. 2005 SHEA Annual Meeting #285.

33. C. diff: Increased Morbidity and Mortality Prospective study of 1719 CDI episodes in 12 Quebec hospitalsProspective study of 1719 CDI episodes in 12 Quebec hospitals –Determine incidence of CDI and complications 22.5 per 1,000 admissions22.5 per 1,000 admissions –Incidence increased with age 30-day attributable mortality was 6.9%30-day attributable mortality was 6.9% –Attributable mortality increased with age 110 (6.5%) required ICU care110 (6.5%) required ICU care 33 (1.9%) required colectomies33 (1.9%) required colectomies Loo VG et al. NEJM 2005;353(23):2442.

34. C. diff: Pathogenicity In general, C. diff strains either possess the entire genetic element (PaLoc) responsible for producing toxin (toxigenic strains) or lack this genetic element and thus, do not cause disease (non-toxigenic strains)In general, C. diff strains either possess the entire genetic element (PaLoc) responsible for producing toxin (toxigenic strains) or lack this genetic element and thus, do not cause disease (non-toxigenic strains)

35. C. diff: Pathogenicity Mutation(s) in the tcd C gene can cause the C. diff strain to produce increased amounts of toxin causing more severe disease.Mutation(s) in the tcd C gene can cause the C. diff strain to produce increased amounts of toxin causing more severe disease. –16 x more toxin A and 23 x more toxin B A binary toxin may also contribute, but clinical significance is not yet known.A binary toxin may also contribute, but clinical significance is not yet known. This “epidemic strain” is PCR ribotype 027, PFGE type NAP1, and restriction endonuclease type B1.This “epidemic strain” is PCR ribotype 027, PFGE type NAP1, and restriction endonuclease type B1.

36. States with BI/NAP1/027 strain of C. difficile DC PR AK HI Recent data: among patients colonized or infected with C. diff, 36% and 63% have the NAP1 strain, respectively

37. CDI: Risk Factors Pittsburgh hospital outbreak (MVA)Pittsburgh hospital outbreak (MVA) OR95%CI Age (per year) 1.021.01-1.04 Diabetes2.11.2-3.6 Organ Transplant 5.82.3-14.6 H2 blocker 2.01.1-3.5 PPI2.41.3-4.4 Clindamycin4.81.9-12.0 Ceftriaxone5.41.8-15.8 *Levofloxacin2.01.2-3.3 Muto et al. ICHE 2005;26:273. *Levofloxacin use significantly increased over the preceding months leading up to the outbreak months leading up to the outbreak

38. CDI: Risk Factors Quebec hospitals OutbreakQuebec hospitals Outbreak –Fluoroquinolone receipt OR 3.9 (2.3-6.6) All fluoroquinolones studies were independently associated with CDIAll fluoroquinolones studies were independently associated with CDI –Cephalosporin receipt OR 3.8 (2.2-6.6) All cephalosporins studies were independently associated with CDIAll cephalosporins studies were independently associated with CDI –PPI, H2 blockers, or chemotherapy were not significantly associated with CDI –All isolates with tcdC gene mutations also had the binary toxin gene Severe CDI was observed in 22 of 132 patients with both genetic elementsSevere CDI was observed in 22 of 132 patients with both genetic elements Severe CDI was not observed in any pt that did not have these genetic elements (p=0.03)Severe CDI was not observed in any pt that did not have these genetic elements (p=0.03) Loo VG et al. NEJM 2005;353(23):2442.

39. CDI: An Antibiotic-Resistance Issue? Pittsburgh hospital outbreakPittsburgh hospital outbreak –No isolates R to metronidazole or vancomycin –85.7% R to clindamycin Clindamycin was a significant riskClindamycin was a significant risk –94.5% R to levofloxacin Levofloxacin was a significant riskLevofloxacin was a significant risk Quebec hospitals OutbreakQuebec hospitals Outbreak –No isolates R to metronidazole, vancomycin or clindamycin Clindamycin was not a significant riskClindamycin was not a significant risk –100% of predominate type isolates R to ciprofloxacin, moxifloxacin, gatifloxacin, and levofloxacin All FQ were associated with increased riskAll FQ were associated with increased risk Muto et al. ICHE 2005;26:273., Loo VG et al. NEJM 2005;353(23):2442.

40. CDI and Fluoroquinolones Characterization of 187 C. diff isolates from 8 healthcare facilities from 2001-2003 and comparison to historic isolatesCharacterization of 187 C. diff isolates from 8 healthcare facilities from 2001-2003 and comparison to historic isolates –An epidemic strain was identified and was responsible for 50% or more of the isolates from most facilities (binary toxin and tcdC deletions in all) –This epidemic strain was in existence since 1984 –Compared to similar historic strains where no R to FQ was detected, all recent strains were R to gatifloxacin and moxifloxacin –Conclusion: A previously uncommon strain of C. diff with variation in toxin genes has become more R to fluoroquinolones and has emerged as a cause of geographically dispersed outbreaks of CDI McDonald LC et al. NEJM 2005;353(23):2433.

41. C. diff: Community Setting 31 yo woman 14 weeks pregnant with twins developed 3 weeks of intermittent diarrhea- stool specimens positive for C. diff31 yo woman 14 weeks pregnant with twins developed 3 weeks of intermittent diarrhea- stool specimens positive for C. diff –Only ABX exposure was TMP-SXT 3 mo prior –Treated but ultimately developed severe disease hospitalized for 18 days –Had recurrent disease 4 days after discharge, spontaneously aborted her fetuses, developed sepsis and died CDC and Philadelphia Department of Public Health launched investigationCDC and Philadelphia Department of Public Health launched investigation

42. C. diff: Community Setting 33 cases of CA-CDI were reported from NH, PA, NJ, OH, all but 1 occurring in 2004-200533 cases of CA-CDI were reported from NH, PA, NJ, OH, all but 1 occurring in 2004-2005 –15 (46%) required hospitalization or an ED visit –13 (39%) had a relapse requiring treatment –8 (24%) reported no ABX exposure in prior 3 months 3 of these cases had exposure to patient with “diarrheal illness” (2 confirmed C. diff)3 of these cases had exposure to patient with “diarrheal illness” (2 confirmed C. diff) –Of those who had received ABX (25 patients) 3 had received <3 doses, 2 had received only 1 dose3 had received <3 doses, 2 had received only 1 dose 10 reported exposure to clindamycin10 reported exposure to clindamycin –10 among peripartum women Transmission to close contacts evident for 4 patientsTransmission to close contacts evident for 4 patients –23 among non-peripartum individuals Ages 6 mo to 72 years (mean 26 years)Ages 6 mo to 72 years (mean 26 years)

43. C. diff: Community Setting The estimated minimum annual incidence of CA-CDI in Philadelphia and its surrounding four countiesThe estimated minimum annual incidence of CA-CDI in Philadelphia and its surrounding four counties –7.6 per 100,000 population –One case for every 5,549 outpatient ABX prescriptions Twice as high as the <1 case per 10,000 cited in earlier studiesTwice as high as the <1 case per 10,000 cited in earlier studies

44. C. diff: Community Setting ConclusionsConclusions –These cases of severe CDI among individuals previously thought to be at low risk might reflect changing epidemiology –Certain features of CDI that have been uncommon in the past might be changing Close-contact transmissionClose-contact transmission High recurrence rateHigh recurrence rate Younger age patientsYounger age patients Lack of ABX exposureLack of ABX exposure –Because reporting was voluntary, the true incidence of CDI is likely higher

45. Clostridium DifficileClostridium Difficile –Emerging issues related to CDI include an increase in overall disease incidence associated with an epidemic strain that contains a mutation for increased toxin production and thus more severe disease with higher risk of death. This strain has an increased rate of resistance to certain antimicrobials, particularly fluoroquinolones, which may be driving the rates. Additionally, the epidemiology of CDI in the community, previously thought to be low risk, may be changing.

46. CDI: Treatment Stop the inciting antibioticStop the inciting antibiotic –Up to 25% will recover without further therapy Metronidazole vs. Vancomycin –Several older retrospective studies comparing oral metronidazole to oral vancomycin Metronidazole just as effective –Response rates >95% Less expensive ($2 day vs. $70 day) Less risk for VRE emergence and spread –A recent prospective observational study Response rate to metronidazole was only 78% –Due to recent emergence of newer strain?

47. CDI: Treatment Metronidazole vs. Vancomycin –Both drugs have good in vitro activity Median MICs <1.0 –Both drugs promote VRE overgrowth in the stool during treatment –Relapse rates after treatment are about the same for both drugs –Controversy regarding gut levels of metronidazole Only present with active disease? Wafa N. AAC 2008;52(7):2403-2406.

48. CDI: Treatment Metronidazole vs. Vancomycin Cure by SOIMetronidazoleVancomycinP-value mild37/41 (90)39/40 (98)0.36 severe29/38 (76)30/31 (97)0.02 Relapse Rate9/66 (14)5/69 (7)0.27 Zar FA. CID 2007;45:302-307.

49. CDI: Treatment Metronidazole vs. Vancomycin Cure by SOIMetronidazoleVancomycinP-value mild26/33 (79)23/27 (85)NS moderate40/53 (75)58/73 (80)NS severe37/58 (65)28/33 (85)<0.05 Relapse Rate29/100 (29)27/103 (23)NS Louie T. ICAAC 2007. Abstract K-4259.

50. CDI: Treatment Metronidazole vs. Vancomycin MetronidazoleVancomycinP-value LOS (days)12.811.5<0.001 Mortality7.9%6.8%0.02 ICU stay23.217.7<0.001 Drug cost$2439$2492NS Hospital cost$16953$14718<0.001 Lahue B. ECCMID 2007. Abstract 1732.

51. CDI: Treatment Appropriate antibiotics directed towards C. diff should be given for 10 days for mild to moderate diseaseAppropriate antibiotics directed towards C. diff should be given for 10 days for mild to moderate disease –Metronidazole (PO or IV), Vancomycin (PO) Most experts recommend starting with metronidazoleMost experts recommend starting with metronidazole Clinicians should be vigilant about monitoring responseClinicians should be vigilant about monitoring response –If disease does not progress, should not consider treatment failure before 6-7 days –Vancomycin may be more appropriate for severe disease Intraluminal or oralIntraluminal or oral –Consider surgery if CDI progresses or if severe

52. CDI: Treatment Nitazoxanide vs. Vancomycin (severe disease) NitazoxanideVancomycinP-value EOT response 8/10 (80)7/10 (70)NS Relapse1/10 (10) NS Sustained response 7/10 (70)6/10 (60)NS Musher D. CID 2009;48:e41-e46.

53. CDI: Treatment Fidaxomicin vs. Vancomycin Package Insert DIFICID 2011. Clinical Response EOTSustained Response DificidVancoDifference (95% CI) DificidVancoDifference (95% CI) Trial 1 88%86%2.6% (-2.9-8.0) 70%57%12.7% (4.4-20.9) Trail 2 88%87%1.0% (-4.8-6.8%) 72%57%14.8% (5.9-23.3%) Some evidence to suggest that Dificid may be better for non-B1 isolates of C Diff when compared to vancomycin (redcued recurrence). Equivalent for B1 isolates.

54. CDI: Treatment Tolevamer (polymer): phase 3- inferior to vancomycinTolevamer (polymer): phase 3- inferior to vancomycin Ramoplanin (antibiotic): phase 3Ramoplanin (antibiotic): phase 3 Rifaximin (antibiotic): effective when used with vancomycin for recurrent diseaseRifaximin (antibiotic): effective when used with vancomycin for recurrent disease Monoclonal antibody: phase 2Monoclonal antibody: phase 2 Vaccine: phase 2Vaccine: phase 2

55. CDI: Recurrent Disease Meta-analysis of 12 studies to identify risks for recurrent diseaseMeta-analysis of 12 studies to identify risks for recurrent disease –Continued use of non-CDI antibiotics OR 4.23 95%CI 2.10-8.55, p<0.001OR 4.23 95%CI 2.10-8.55, p<0.001 –Concomitant receipt of antacid medications OR 2.15 95%CI 1.13-4.08, p=0.02OR 2.15 95%CI 1.13-4.08, p=0.02 –Older age OR 1.62 95%CI 1.11-2.36, p=001OR 1.62 95%CI 1.11-2.36, p=001 Garey KW. JHI 2008;70:298-304.

56. CDI: Treatment No consensus on recurrent diseaseNo consensus on recurrent disease –Alternative agents, pulsed or tapering vancomycin courses –Ion-exchange resins and polymers –IVIG: some positive results in case reports Do not treat asymptomatic colonizationDo not treat asymptomatic colonization –Current therapies not effective for this purpose Vancomycin effects not sustained and may place pts at risk for prolonged carriage after treatmentVancomycin effects not sustained and may place pts at risk for prolonged carriage after treatment Can only obtain significant intraluminal levels of metronidazole in presence of diarrheaCan only obtain significant intraluminal levels of metronidazole in presence of diarrhea

57. CDI: Alternative Regimens Meta-analysis of RR by Type of Probiotic for Prevention of Antibiotic Associated DiarrheaMeta-analysis of RR by Type of Probiotic for Prevention of Antibiotic Associated Diarrhea #RCT Pooled RR 95%CI, p-value Saccharomyces60.37 0.26-0.52, <0.0001 Lactobaccillus60.31 0.13-0.72, 0.006 McFarland LV. Am J Gastro 2006;101:812. Meta-analysis of 6 RCT for Prevention of CDIMeta-analysis of 6 RCT for Prevention of CDI –RR 0.59, 95%CI 0.41- 0.85, p=0.005 –Only Saccharomyces showed significant reduction for recurrent CDI

58. CDI: Alternative Regimens 2 patients died of unrelated causes2 patients died of unrelated causes 1 patient had recurrent disease (6.3%)1 patient had recurrent disease (6.3%) 15 had no recurrent disease at 90 day follow-up15 had no recurrent disease at 90 day follow-up

59. C. Diff: Transmission Two major potential reservoirs of C. diff in hospitals are patients and inanimate objectsTwo major potential reservoirs of C. diff in hospitals are patients and inanimate objects Continued pressure from indiscriminate antibiotic useContinued pressure from indiscriminate antibiotic use –Failure to stop antibiotics when they are no longer indicated Patients with symptomatic intestinal infection probably contribute mostPatients with symptomatic intestinal infection probably contribute most –Contamination of the environment due to persistence of highly resistant spores Can persist for many weeks or months after the patient has left the environmentCan persist for many weeks or months after the patient has left the environment –Personnel hand carriage probably accounts for the majority of hospital transmission

61. Original (Incorrect) Hypothesis for C. diff Hospital Infection Hospitalization C. Diff acquisition Antimicrobials C. Diff disease

62. Alternative Hypothesis for C. diff Hospital Infection Hospitalization C. Diff acquisition Antimicrobials C. Diff disease C. Diff acquisition Asymptomaticcolonization Many factors associated with development of disease

63. Asymptomatic C. diff Colonization Data from four prospective studies in which rectal swabs were obtained weekly from hospitalized patients:Data from four prospective studies in which rectal swabs were obtained weekly from hospitalized patients: –Rates of CDI in non-colonized patients was 3.6% compared to 1.3% in colonized patients (p=0.02) –Rate also significantly decreased when only patients who received antibiotics were analyzed (p=0.02) Lancet 1998;351:633-636

64. Clostridium difficile: Control Consider two distinct but related approachesConsider two distinct but related approaches –Efforts directed at interrupting horizontal spread (keep patient from acquiring organism) –Efforts to minimize the possibility that exposure will result in infection (reduce individual risk of disease)

65. Control Measures: Prevention of CDI Follow antimicrobial usage restrictionsFollow antimicrobial usage restrictions Avoid electronic thermometersAvoid electronic thermometers Dedicate patient care itemsDedicate patient care items Use full barrier precautions for CDI ptsUse full barrier precautions for CDI pts Place CDI pts in private roomPlace CDI pts in private room Perform appropriate hand hygienePerform appropriate hand hygiene Perform adequate environmental decontamination (bleach)Perform adequate environmental decontamination (bleach) Educate HCWs regarding CDIEducate HCWs regarding CDI SHEA/IDSA Practice Recommendations. ICHE 2008;29:Suppl 1. SHEA/IDSA Practice Recommendations. ICHE 2008;29:Suppl 1.

66. Hand Hygiene and C. diff Risk Hand washing with soap or chlorhexidine is equally effective in removing spores of C. diff from the seeded hands of volunteersHand washing with soap or chlorhexidine is equally effective in removing spores of C. diff from the seeded hands of volunteers Alcohol hand hygiene products are not sporicidal and not likely to reduce the burden of spores on hands when used without hand washingAlcohol hand hygiene products are not sporicidal and not likely to reduce the burden of spores on hands when used without hand washing CDI outbreaks have NOT been directly related to use of alcohol hand hygiene productsCDI outbreaks have NOT been directly related to use of alcohol hand hygiene products

67. Control Measures: Prevention of CDI Approaches that should not be considered for routine prevention –Testing of asymptomatic patients –Repeat testing of CDI pts after successful therapy Unresolved issues –Use of contact precautions by family members –Standing nursing orders for testing –Restricting gastric acid lowering medications SHEA/IDSA Practice Recommendations. ICHE 2008;29:Suppl 1. SHEA/IDSA Practice Recommendations. ICHE 2008;29:Suppl 1.

68. Prevention of C. diff Hospital Infection Hospitalization Antimicrobials C. Diff disease C. Diff acquisition Asymptomaticcolonization Give non-toxigenic C. diff

69. CDI: Treatment and ControlCDI: Treatment and Control –Effective treatment regimens have been developed for mild to moderate disease which include metronidazole, vancomycin, and fidaxomicin. Severe disease may require alternative uses of traditional drug regimens and possibly adjunctive agents. The transmissibility of C. diff has been well described in healthcare facilities and control measures have been recommended. Novel prevention methods are being considered.

70. Summary Clostridium difficile remains an important nosocomial pathogenClostridium difficile remains an important nosocomial pathogen The epidemiology of Clostridium difficile is changingThe epidemiology of Clostridium difficile is changing –Increased rates in acute care and long term care facilities –Increased morbidity and mortality –Possibly due to a genetically altered strain with increased virulence Effective treatment regimens existEffective treatment regimens exist –Study of new treatment regimens should continue Effective control measures have been describedEffective control measures have been described –Study of new or enhanced control measures should continue

71. Questions…