Presentation on theme: "Epidemiology and Prevention of Clostridium difficile"— Presentation transcript:
1 Epidemiology and Prevention of Clostridium difficile W.I.P.E. Out Those BugsMay 2, 2014Kavita K. Trivedi, MDPrincipal, Trivedi Consults, LLCAdjunct Clinical Professor of Medicine, Stanford University School of Medicine
2 ObjectivesDescribe the changing epidemiology of Clostridium difficile infections (CDI) in the United StatesReview recent research on prevention of CDIDiscuss how to apply accepted infection prevention practices for CDI in healthcare settings
3 Background Gram positive, spore forming rod Obligate anaerobe Toxin A and Toxin BRequired to cause diseaseClostridium difficile infection (CDI, formerly CDAD)Most common cause of healthcare- associated diarrheaFecal-oral transmissionCan be community-associatedKey Points:Can produce at least 2 enterotoxins: Toxin A and Toxin BToxin B is particularly toxic and causes diseaseAntibiotic exposure can trigger expression of the toxins
4 Background: Adults2-5% of healthy adults have C. difficile colonization of the colon20-40% of hospitalized adults are colonized with C. difficile
5 Background: ChildrenColonization rates of up to 70% have been reported in children < 1 yearBy 2 years the ‘normal’ colonic flora is established and colonization decreases to the rate of healthy adults
6 Epidemiology Range from mild to severe Starting in 2002, changes in C. difficile noted, first in QuebecIncreased incidence (1991/19922003)36/100,0000156/100,00065 and older: from 102/100,000 to 866/100,000Increased complicationsComplicated disease: 7.1%18.2%Death within 30 days: 4.7%13.8%Comparing 1991/19922003Lisa Winston, MD; Pepin et al., CMAJ 2004;171:466-72
8 C. Difficile Infection (CDI) Incidence and severity have increased with dissemination of BI/NAP1 isolatesHistorically uncommon – epidemic since 2000Increased virulenceIncreased toxin A and B productionPolymorphisms in binding domain of toxin BIncreased sporulationIncreased resistance to fluoroquinolonesHigher MICs compared to historic strains and current non-BI/NAP1 strainsEarly diagnosis and treatment are required to reduce morbidity/mortalityMcDonald et al. N Engl J Med. 2005;353: ; Warny et al. Lancet. 2005;366:Stabler et al. J Med Micro. 2008;57:771–5; Akerlund et al. J Clin Microbiol. 2008;46:1530–3
10 Clostridium difficile Incidence and Mortality Are Increasing No. of CDI Cases per 10,000 DischargesAnnual CD-related Mortality Rate per Million PopulationElixhauser A, et al. Healthcare Cost and Utilization Project: Statistical Brief #50. April Available at: Accessed March 10, 2010.Redelings MD, et al. Emerg Infect Dis. 2007;13:
11 Cost of CDI in US CDI accounts for 336,000 hospitalizations annually Aggregate hospital costs exceed $8.2 billion annuallyPatients with principal CDI diagnosis remain hospitalized for 6.9 days at a cost of $10,100/stayPatients with secondary CDI diagnosis remain hospitalized for 16.0 days at a cost of $31,500/stay.CDI disproportionately affects the elderlyCMS pays for 68% of CDI hospital staysLucado J, Gould C, Elixhauser A. Clostridium difficile infections (CDI) in hospital stays, HCUP Statistical Brief124. January Rockville, MD: Agency for Healthcare Research and Quality. Accessed December 27, 2011.
12 Pathogenesis of CDI Key steps Acquisition of C. difficile Alteration of colonic floraGrowth of C. difficile and elaboration of toxinsPoorly understood additional factor (s?)Key Points:Data is challenging our previous understanding of C.diff pathogenesisPrevious conception: Colonized with C. Diff, get antibiotics, get C. diff infectionBut, it’s not that simple. It is a multi-step process: acquire C. diff (often in the hospital), then bowel flora is altered through antibiotic use, conditions promote C. diff growth and tissue damageThere are still factors that we don’t understandGerding D N , Johnson S. CID 2010;51:
13 CDI Risk Factors Antimicrobial exposure Acquisition of C. difficile Advanced ageUnderlying illnessImmunosuppressionTube feeds? Gastric acid suppressionInstructor Notes: Acknowledge C. Gould – CDCKey Points:These risk factors are similar to the risk factors for MDRO gram negatives.The impact of tube feeding and gastric acid suppression are both pathogenically and programmatically limited. Neither one imparts the independent high risk of a patient developing CDI. While they may impact development of CDI in an individual patient, neither is particularly amenable to programmatic intervention.
14 Risk Factors Antimicrobial exposure Acquisition of C. difficile Advanced ageUnderlying illnessImmunosuppressionTube feeds? Gastric acid suppressionMajor modifiable riskfactors
15 C. difficile Hospital Epidemiology Use of antibiotics is frequentEnvironmental contamination by C. difficile is commonSpores are difficult to eradicatePersonnel carry C. difficile on their handsAsymptomatic patients carry C. difficile
16 Major Modifiable Risk Factors Instructor Note:This slide leads into topics introduced in the next two slides.Key Point:Other approaches to modifying risk factors include:block transmission of C. diff with barrier precautions and environmental cleaningpreventing unnecessary/inappropriate antibiotic useGerding D N , Johnson S. CID 2010;51:
17 Major Modifiable Risk Factors Antibiotic ExposureAntibiotic StewardshipAcquisition of C. difficileKey Points:How do we use antibiotic exposure interventions to reduce C. diff infections?Optimizing Environmental Cleaning and Hand Hygiene
19 Antibiotic misuse adversely impacts patients - Clostridium difficile Antibiotic exposure is the single most important risk factor for the development of Clostridium difficile associated disease (CDAD)Up to 85% of patients with CDAD have antibiotic exposure in the 28 days before infectionChang HT et al. Infect Control Hosp Epidemiol 2007; 28:926–931.
20 Antimicrobials Predisposing to CDI Very Commonly RelatedLess Commonly RelatedUncommonly RelatedClindamycinAmpicillinAmoxicillinCephalosporinsFluoroquinolonesOther penicillinsSulfonamidesTrimethoprimCotrimoxazoleMacrolidesCarbapenemsAminoglycosidesBacitracinMetronidazoleTeicoplaninRifampinChloramphenicolTetracyclinesDaptomycinTigecyclineInstructor Notes:Acknowledge E. Dubberke, Wash UKey Points:antimicrobials predispose people to CDI through the alteration of their colonic floraCDI is classically linked to Clindamycin, but we’ve learned that nearly any antibiotic can alter flora sufficiently to allow C. diff growthThe antibiotics commonly related to CDI are just a list of the commonly used antibiotics!Uncommonly associated antibiotics have no or very little anaerobic activity. This may be significant since disruption of the normal anaerobic bowel flora appears to be a key element in C. diff pathogenesis.Bouza E, et al. Med Clin North Am. 2006;90:Loo VG, et al. N Engl J Med. 2005;353:
21 Impact of Fluoroquinolone Optimization on Rates of Hospital-Onset CDI HO-CDAD cases/1,000 pd200520062007Month and YearInfect Control Hosp Epidemiol Mar;30(3):
22 66 Studies had meaningful data analysis 16 Studies evaluated microbiologic outcomes4 Studies – Favorable8 Studies +/-4 Studies—no effectKey Points:Group out of UK did a systematic review of antimicrobial policies and correlated them with the impact on C. diff infectionsOnly 16/309 represented carefully designed studies that could objectively asses whether or not an antibiotic management program could impact a clinical condition such as CDIOf the 16 studies evaluated, 4 had compelling and supporting data that stewardship effectively reduced the rate of CDI, 8 had some other favorable effect, and 4 had no effect.In sum, of the 16 studies evaluated, 12 of them showed that antimicrobial policies had a positive effect.
23 Antimicrobial Stewardship Impact on C. difficile Disease Key Points:This is another slide illustrating the relative impact of antimicrobial stewardship on CDIsThe graph shows 4 different potential outcomes: Sudden increase in CDI, Sudden decrease in CDI, Sustained decreased effect on CDI, Sustained increase effect on CDIX axis: The immediate effect of antimicrobial stewardship on CDI. The further to the left of the y-axis, the more impact it had. 4 papers showed a sudden decrease in CDI.Y axis: The sustained impact of antimicrobial stewardship on CDI. 4 papers showed a sustained positive effect on CDI.The dotted line shoes 95% confidence intervals. The study by Calli was limited to an ICU setting whereas the studies by Cimino and Carling represented highly effective hospital wide stewardship programs that might not be generalizable.This shows that antimicrobial stewardship programs can have both an immediate and a sustained impact on C. diff infections.Instructor Note:The modeling used in the study is extremely sophisticated and transportable. Recommend that participants in this program interested in analyzing multisite interventions study the methods used in this paper. Mark Wilcox, the senior author, is widely recognized in Great Britain for his work related to epidemiology and pathogenesis of CDI and other HAPs.
24 ASP Make a Difference with Hospital-Associated CDI Tertiary Care Hospital; Québec, Canada ( )This particular study looks at implementing enhanced infection control for C. diff and having a minimal impact (Editor’s note: In reading the study, there may have been some limitations in the approaches that were taken with respect to hand hygiene and environmental services cleaning). But then, when combined with a second intervention in antibiotic optimization and stewardship, you can see that they were able to decrease the targeted antibiotics (2nd and 3rd gen cephs, macrolides, cipro, clinda) in this study, as directed by the yellow-orange line, and, at the same time, had a decrease in their C. diff prevalence or incidence in the hospital. Interesting to note that levoflox/moxi use was stable or increased but important to note that total usage decreased. There was a clear sustained, statistically significant decrease in CDI over time with a sustained decrease in abx utilization.Valiquette, et al. Clin Infect Dis 2007;45:S112.
25 ASP Community Hospital Example Team: ID pharmacists, ID physiciansTarget: 8 target antimicrobialsInterventions: Prospective audit of new antimicrobial starts and weekly useMeasure: Significant reductions in Clostridium difficile rates, antimicrobial utilization and pharmacy costsMalani, AN et al. Clinical and economic outcomes from a community hospital's antimicrobial stewardship program. American Journal of Infection Control 2012 May 9.
27 C. difficile and the Environment Level of contamination may be highSpores survive > 5 monthsKey Points:C. diff can reside on inanimate objects as a spore for months Contamination of the environment with C. diff spores contributes to transmissionWhat is interesting is that data shows that hospital surfaces have diffuse spread of C. diff spores but a low level contamination. High levels of contamination of C. diff spores are not needed to cause infection, though (acquisition dose is 10 or less spores).Infective dose < 10 spores
28 C. Difficile and the Environment Key Points:This graph shows the % of skin contamination stratified by patients that have C. diff infection, are colonized with C. diff but have no symptoms, or are not even carriers of C. diff, but who are in hospital beds.The bars are color coded according to different parts of the body with skin contaminated by C. diff: Skin (anywhere), groin, chest/abdomenOverall, this study shows that C. diff spores are almost as common on the skin of carriers as they are in symptomatic patients. How many undiagnosed carriers are there in the average hospital? Remember, we only test symptomatic patients.It’s also important to remembers that many patients recovering from acute CDI excrete C. diff for months after becoming asymptomatic.Sethi et al. 2010
29 C. Difficile and the Environment Key Points:Similarly, this same study showed that a) environmental contamination associated with asymptomatic patients is almost as great as with symptomatic patients; b) 30% of surfaces around non carriers were also culture positive.What does the latter mean? (Ask the audience)Answer: these spores most probably came from prior room occupants in the setting of suboptimal disinfection cleaning.Sethi et al. 2010
30 C. Difficile and the Environment Key Points:This quantitative study classified different surfaces as near or distant from patients with acute CDI.It was discovered that both near and distant surface contamination associated with symptomatic patients was only 50% less than the ill patients’ hands.Also of note is the fact that C. diff could be found on near and distant environmental surfaces on wards that had not had a recognized patient with CDI in at least six months.While it certainly is possible that these C. diff spores had been sitting alive and well on these surfaces for six or more months, it is also possible that recently admitted asymptomatic carriers contaminated the surrounding environment which was not, in either case, being effectively cleaned.
31 Is the environment important in C. difficile transmission? Key: Environmental colonization is important, widespread, and must not be ignored.
32 Persistence of sporesKey Points:This study was presented at ICAAC in 2008 and published in ICHE January, 2011Looks at the incidence of CDI in patients with respect to whether they were in a room previously occupied by a patient with C. diffIf a patient was in a room previously occupied by a C. dif f positive patient, that new patient has >110% higher risk of developing CDI.This does not show causation, but perhaps it is supporting evidence that the environment is involved with transmissionIn multivariate analysis, OR for prior room occupant with CDI = 2.4 ( )Adjusted for age, APACHE score, PPI, abx use… but not for length of stayShaugnessy et al. Infect Control Hosp Epidemiol Mar;32(3):201-6.
33 Can disinfection cleaning decrease environmental contamination? Key Point:Answer: Yes
34 Studies reporting a favorable impact of enhanced environmental hygiene during a CDI outbreak Key Point:Over the years researchers reporting quasi-experimental studies have repeatedly reported that more thorough environmental cleaning had a favorable impact on C. difficile outbreak setting transmission.While this phenomenon might merely be a reflection of an otherwise independent epidemic curve, the large number of studies, taken together, provide substantial support for the likelihood that improving environmental hygiene and disinfection cleaning can favorably impact CDI incidence.
35 Culture based evaluation - Pre-intervention - after routine terminal cleaning- after terminal cleaning by the research staff- following education of the ES staff and administrative interventionsKey Points:This landmark study carefully evaluated the impact of routine and subsequently more thorough environmental cleaning on C. diff environmental surface contamination.
36 Percentage of C. difficile-positive cultures n=9 rooms 8070605040302010Percent positiveBefore cleaningAfterhousekeepingcleaningdisinfection byresearch team*BedrailBedside tablePhoneCall buttonToiletDoor handleKey Points:Even when you are using bleach, as was done in this study, usual cleaning of hospital rooms is not particularly effective at reducing C. diff contaminationContamination of the bedrail, toilet, went down but contamination of the phone, call button, and bedside table barely changed after routine cleaningBut then look what happened when the same rooms were thoroughly cleaned by a “research team” (the investigators). Only one culture was positive. Subsequently similar results were found after carefully educating the environmental services workers.Unfortunately, these results were not sustained and contamination rates rapidly returned to the “after housekeeping levels” due to lack of feedback or long-term programmatic intervention (personal communication, Curtis Donskey, senior author).*Similar results found after ES cleaning following interventionsEckstein et al, BMC Infect Dis Jun 21;7:61.
37 Can improved disinfection/cleaning lead to decreased CDI? Answer: Yes
38 Greater New York CDI Collaborative 40 Hospitals – New York area,Pre-intervention rate – 8.1/ 10,000 PtDSimilar education, check sheet and self reporting of thoroughness of terminal cleaning. Glitterbug lotion used for some teaching (not monitoring).70% of Hospitals saw an average decrease of 26% in HO CDI (Mean for the system = 15%)Key Points:This very important study is hopefully moving towards publication.It’s the only large multi-site study of the impact of improved environmental hygiene on endemic CDI rates and clearly showed the short term impact a focal programmatic effort to improve environmental hygiene had on CDI rates in many participating hospitals.Source: Barbra Smith, RN CIC and Brian Koll, M.D. project Coordinators. APIC presentation.
40 CDC Prevention Strategies Supplemental StrategiesCore StrategiesHigh levels of scientific evidenceDemonstrated feasibilitySome scientific evidenceVariable levels of feasibilityThere are two approaches to controlling C. diff described in CDC recommendations. There are core strategies that are better supported by the scientific literature and less well proven supplemental strategies.
41 Environmental Cleaning CoreSupplementalCleaning and disinfection of equipment and environmentConsider sodium hypochlorite in outbreak or hyper endemic settingsRoutinely assess adherence to protocols and adequacy of cleaningReassess adequacy of room cleaning and address issuesUse sodium hypochlorite (bleach) – containing agentsKey Points:C. diff is very hardy. You need to use bleach because it isn’t susceptible to the usual agents used(although bleach is not strongly recommended, it is the standard for known c. diff in many hospitals)The rigor of cleaning needs to be assessed. You can’t just go by how it looksDubberke et al. Infect Control Hosp Epidemiol 2008;29:S81-92Cohen et al. Infect Control Hosp Epidemiol 2010;31
42 Contact Precautions Core Supplemental Gloves/gowns on room entry Private room (preferred) or cohort with dedicated commodesDedicated equipmentMaintain for duration of diarrheaMeasure complianceExtend use of Contact Precautions beyond duration of diarrhea (hospitalization)Presumptive isolationUniversal glove use on units with high CDI ratesIntensify assessment of complianceKey Points:Contact Precautions are recommended for C. diffThere has been a suggestion that Isolation leads to worse patient satisfaction and patient outcomes (anxiety, depression, worse healthcare) but these are not sufficiently explored to have an impact on the recommendation to use Contact Precautions.
43 Hand Hygiene Supplemental Core Soap and water for hand hygiene before exiting room of a patient with CDIIntensify assessment of complianceCoreHand hygiene based on CDC or WHO guidelinesSoap and water preferentially in outbreak or hyper endemic settingsMeasure complianceKey Points:There are guidelines that explain how to monitor hand hygieneSince you can’t use bleach on your hands, patients and HCWs need to use soap and water when interacting with patients that have CDI
44 Diagnostic Testing Core Supplemental Laboratory-based alert system for immediate notification of positive test resultsEvaluate and optimize testing for CDI
45 Evaluate and Optimize Testing for CDI Toxin A/B enzyme immunoassays have low sensitivities (60-80%)Despite high specificity, poor test ordering practices (i.e. testing formed stool) may lead to false positivesConsider more sensitive diagnostic paradigms but apply judiciouslyRestrict testing to unformed stool onlyFocus testing on patients with > 3 unformed stools within 24 hoursRepeat testing no more than every 5-7 days if negativeRequire expert consultation for repeat testing within 5 daysTest of cure is not recommendedKey Points:This slide expands on the complexities of testing for CDIThere needs to be uniform and consistent testing strategiesVERY IMPORTANT: Patients should only be tested if they have loose stoolsMost hospitals are using the 2 step testing method nowPeterson et al. Ann Intern Med 2009;15:176-9.Cohen et al. Infect Control Hosp Epi 2010; 31 (5):
48 Two-Step Testing Utility related to Promoted to enhance sensitivity Sensitivity of initial screenSensitivity of GDH EIA screen 76% to 100%Cost of confirmatory test alone versus screen plus confirmatory testCost of false positive test (not quantified)Promoted to enhance sensitivityActually enhances positive predictive value of confirmatory testIncreased prevalence of diseaseInstructor Notes: Acknowledge E. Dubberke, Wash UKey Points:Note again a growing consensus around using GDH plus/minus EIA for screening and PICR for confirmation if GDH is positive and EIA is negative when using a combined testing system.This approach needs to be standardized and promoted if we are to move ahead with understanding epidemiology and impact of preventive measures related to CDI.So, if each of these tests are flawed, maybe the solution is to use more than one to diagnose C. diff.This method will improve the positive predictive value, but will increase the cost.
49 Conclusions CDI is the most serious, frequent and costly HAI Decreased antibiotic exposure and stewardship optimization are important in preventing CDIOptimizing environmental hygiene is becoming recognized as central to controlling CDIAll hospitals should be in compliance with CDC Core Recommendations49
50 CDI and Infection control Gloves + gowns for duration of diarrheaWash with soap and water (epidemic setting)Private roomsDedicated commodeBleach cleaningAntimicrobial stewardshipCohen et al., Infection Control and Hospital Epidemiology, 2010; 31:
51 ConclusionsGerding D N , Johnson S. CID 2010;51: