Clostridium difficile Infection: Diagnosis and Management

Transcription

1 Clostridim difficile Infection: Diagnosis and Management Brian Viviano D.O. Objectives Identify patients at increased risk of C-diff infection Pathogenesis of C-diff Identify best tests for diagnosis of C-diff Define flminant C-diff and compare treatment strategies Treatment, prevention and control of C-diff and recrrent C-diff 1

2 Case stdy 42 year old female with history of essential hypertension and COPD presents to ED complaining of 24 hors of intractable, diffse abdominal pain and diarrhea. Patient reports fol smelling stools over the previos 24 hors. Blood work revealed WBC-24,000 and CT showed diffse colonic thickening. Patient has been in normal health with the exception of a URI treated with antibiotic 6 weeks ago. 2

3 Clostridim Difficile Spore-forming rod Infection typically follows se of broad spectrm antibiotics- ampicillin, clindamycin, cephalosporins Wipe ot the normal intestinal bacterial flora, allowing the pathogenic Clostridim difficile to sperinfect the colon Symptoms are cases by exotoxins Toxin A- cases diarrhea Toxin B- cytotoxic to colonic cells Associated antibiotics 3

4 Clostridim difficile Infection is defined by the presence of symptoms (diarrhea) and either a positive stool toxin or colonoscopic/histologic findings consistent with psedomembranos colitis (next slide). Presence of symptoms are necessary and patients withot symptoms shold not be tested as they can be carriers and do not reqire treatment. Unnecessary cost and treatment Psedomembranos colitis Endothelial damage from the initial event or disease process cases small areas of necrosis in the srface epithelim. The erption of netrophils, nclear debris, and other inflammatory elements from the lamina propria onto the epithelim then leads to psedomembrane formation. 4

5 Estimated Annal U.S. Brden 453,000 CDI cases 1 293,000 healthcare-associated 107,000 hospital-onset 104,000 nrsing home-onset 81,000 commnity-onset, healthcarefacility associated 160,000 commnity-associated 82% associated with otpatient healthcare exposre Overall, 94% of CDI cases related to healthcare 29,000 deaths $4.8 billion in excess healthcare costs 2 Estimated U.S. Brden of CDI, According to the Location of Stool Collection and Inpatient Health Care Exposre, CO-HCA: Commnity onset healthcare-associated NHO: Nrsing home onset HO: Hospital onset 1. Lessa et al. N Engl J Med 2015; 372(9): Dbberke et al. Clin Infect Dis 2012; 55:S Clostridim difficile- Incidence An estimated 500,000 cases yearly in United States Increased risk with the following Age > 65 Female Cacasian Healthcare exposre Antibiotic exposre Inflammatory bowel disease- also carries increased risk of recrrence and colectomy PPI?- 50% increase risk of recrrence Stem cell (9-fold increased risk) and solid organ transplant recipients (5-fold increased risk) ESRD on dialysis. (2-2.5-fold increased risk) Malignancy- especially if actively treated with chemotherapy C-dif has srpassed MRSA as most common case of healthcare associated infection 5

6 Pathogenesis of CDI 1. CDI spores srvive in the environment for long periods of time. Following ingestion, they traverse the acidic environment of the stomach. 3. Altered lower intestine flora (de to antimicrobial se) allows proliferation of C. difficile in colon. 4. Toxin A & B Prodction leads to colon damage +/- psedomembrane. 2. Spores germinate within the intestine. Snenshine & McDonald Cleve Clin J Med 2006; 73(2): Clostridim difficile- Rotes of transmission Hands of healthcare personnel, transiently contaminated with spores, and environmental contamination are predicted as main vectors Instrments- rectal thermometers etc Family members 6

7 Clostridim Difficile- Diagnosis Who shold we test- patients with 3 nformed stools in 24 hors Types of stool tests Enzyme immnoassay. The enzyme immnoassay (EIA) test is faster than other tests bt isn't sensitive enogh to detect many infections and has a higher rate of falsely normal tests. Polymerase chain reaction. This sensitive moleclar test can rapidly detect the C. difficile toxin B gene in a stool sample and is highly accrate. GDH/EIA. Some hospitals se a gltamate dehydrogenase (GDH) in conjnction with an EIA test. GDH is a very sensitive assay and can accrately rle ot the presence of C. difficile in stool samples. Cell cytotoxicity assay. A cytotoxicity test looks for the effects of the C. difficile toxin on hman cells grown in a cltre. This type of test is sensitive, bt it is less widely available, more cmbersome to do and reqires 24 to 48 hors for test reslts. Some hospitals se both the EIA test and cell cytotoxicity assay to ensre accrate reslts. Available Tests 7

8 Gidance from the American Society for Microbiology Toxin A/B enzyme immnoassays have low sensitivity and shold not be sed as stand alone tests. 1 Highly sensitive screening tests like gltamate dehydrogenase antigen assays (GDH) shold have positive reslts confirmed. Ncleic acid amplification that detects C. difficile toxin genes may be sed as a stand alone test. Repeat testing, testing of formed stool, and testing for cre shold be avoided. 2 Regardless of testing method, ensre appropriate testing to optimizing test performance! 1. Am Soc Microbiol, Dbberke et al. Infect Control Hosp Epidemiol 2014; 35 (6): Clostridim Difficile- Diagnosis Important to remember, if CDI is sspected, do not delay treatment. Empiric treatment is extremely important in preventing complications Do not perform repeat testing (within 7 days) dring the same episode Increases diagnostic yield only 2% If epidemic is sspected- repeat testing may be warranted vs empiric treatment 8

9 Gidance for Appropriate Testing Tools that gide clinical decision making, sch as algorithms, can assist in ensring appropriate testing Example of a CDI decision tool from Vanderbilt University Medical Center 1. Dbberke et al. Infect Control Hosp Epidemiol 2014; 35(6): Vanderbilt University Medical Center: 17 Flminant Clostridim Difficile Infection In prior gidelines this was referred to severe, complicated CDI Hypotension Shock Iles Megacolon Important to identify early becase treatment is different initially 9

10 Infection prevention and control Accommodate patients with CDI in a private room with a dedicated toilet to prevent transmission Healthcare personnel mst se gloves and gowns pon entry to a room of a patient with CDI These precations shold be institted if CDI sspected while testing completed Contine contact precations for 48 hors after resoltion of diarrhea Hand washing prior and after patient contact is reqired. If direct contact with stool, handwashing with soap and water preferred Patient shold wash hands and shower when able Disposable eqipment shold be sed if possible and resable eqipment shold be thoroghly cleaned sporicidal disinfectant Infection prevention and control Minimize the freqency and dration of high risk antibiotic therapy Floroqinolones, clindamycin, cephalosporins Most instittions shold have antibiotic stewardship program Proton pmp inhibitors There is an epidemiologic risk associated with PPI and CDI Minimize se in high risk patients Insfficient evidence for discontination of PPI s Probiotics- Insfficient evidence that they redce CDI Does redce antibiotic associated diarrhea 10

11 Treatment Discontine therapy with the inciting antibiotic agent as soon as possible Evidence shows this will decrease clinical response and increase recrrence rates Antibiotic therapy for CDI shold. Be started empirically for sitations where a sbstantial delay in laboratory confirmation is expected or severe disease Treatment Vancomycin or fidaxomicin is now first line Vanco 125mg PO QID Fidaxomicin 200mg PO BID Treat for 10 days Prior gidelines sed disease severity to gide treatment decisions Stdies since then have showed decreased response and high recrrence in metronidazole grops 11

12 Flminant Clostridim Difficile Infection Initial treatment of choice- Vancomycin 500mg PO QID Metronidazole 500mg IV q 8 hors If iles present- Vancomycin 500mg in 100mL NS per rectm q 6 hors Metronidazole 500mg IV q 8 hors If iles or toxic megacolon patient shold admitted to ICU with srgical consltation Srgery of choice- sbtotal colectomy with rectal sparing Diverting loop ileostomy with colonic lavage may lead to improved otcomes Rising WBC (>25,000) or rising lactate level is associated with high mortality and if occrs early srgery indicated Recrrent Clostridim Difficile Infection Prior gidelines state repeat C-dif treatment with same regimen as initial infection Now First recrrence treated with one of the following Vancomycin taper/plse dosing Fidaxomicin 200mg BID x 10 days Vancomycin can be sed in a standard 10 day treatment if metronidazole was sed initially If additional recrrence occrs Vancomycin taper/plse dosing Standard Vancomycin followed by rifaximin 400mg for 20 days Fecal transplant 12

13 Vancomycin taper/plse dose 125mg QID for days then 125mg BID for 7 days then 125mg daily for 7 days then 125mg q2-3 days for 2-8 weeks Mechanism- C. Difficile vegetative forms will be kept in check while allowing restoration of normal microbiota Fecal Microbiota Transplant Patient with recrrent have significant disrption of the intestinal microbiome diversity and decreased bacterial poplation nmbers Instillation of processed stool collected from a healthy donor into the intestinal tract of patients with recrrent CDI Effective % depending on rote of instillation Stdies of rote of transmission and long term conseqences are ongoing The designated stool donor shold ndergo screening of blood and feces prior to the stool donation Disqalifying factors- antibiotic in prior 3 months, IBD, malignancy, chronic infection, atoimmne disease, immnosppressive medications Typically indction corse of 3-4 days of vancomycin prior 13

14 Probiotics Several have shown promise in preventing CDI recrrence bt none have shown reprodcible efficacy in clinical trials Saccharomyces bolardii Lactobacills Cholestyramine In patients with refractory disease give 4g PO 3-4 times daily Works by binding Toxin A/B Use in adjnct with antibiotics- Mst separate by 3 hors as it will bind Can contine for several weeks after antibiotic regimen if needed. 14

15 Clostridim difficile Following treatment, there is no reason to retest stool as patient may have colonized and wold reslt in nnecessary treatment May discontine contact precations once diarrhea free for 48 hors Antibiotic overse has led to increase in Clostridim difficile colitis and recrrence. Limiting sage throgh self monitoring and antibiotic stewardship programs Smmary Review yor facilities diagnostic stdies and nderstand the S/S of each Only test patient s with diarrhea Initiate contact precations once CDI sspected First line treatment is now vancomycin Prevention is key- contact precations, hand washing, limit antibiotic sage 15

16 Qestions References 2007 Gideline for isolation precations: preventing transmission of infectios agents in healthcare settings. Centers for Disease Control and Prevention Web site. Pblished Updated December 9, Accessed Febrary 24, Abad C., Fearday A., & Safdar N. (2010). Adverse effects of isolation in hospitalized patients. J Hosp Infect, 76, Ahyow L., Lambert P., Jenkins D., Neal K., & Tobin M. (2013). Occpancy rates and hospital-acqired Clostridim difficile infection: A cohort stdy. Infect Control Hosp Epidemiol, 34, A practical gidance docment for the laboratory detection of toxigenic Clostridim difficile infection. American Society of Microbiology Web site. Pblished September 21, Accessed Febrary 24, Berhe M., Edmond M., Bearman G. (2006). Measrement and feedback of infection control process measres in the intensive care nit: Impact on compliance. Am J Infect Control, 34(8), Bliss D.Z., Johnson S., Savik L., Clabots C.R., Willard K., Gerding D.N. (1998). Acqisition of Clostridim difficile and Clostridim difficile associated disease in hospitalized patients receiving tbe feeding. Ann Intern Med, 129, Boblsky G.S., Al-Nassir W.N., Riggs M.M., Sethi A.K., & Donskey C.J. (2008). Clostridim difficile skin contamination in patients with C. difficile-associated disease. Clin Infect Dis, 46(3),

17 References Boyce J.M., Havill N.L., Havill H.L., Mangione E., Dmigan D.G., Moore B.A. (2011). Comparison of florescent marker systems with 2 qantitative methods of assessing terminal cleaning practices. Infect Control Hosp Epidemiol, 32(12), Boyce J.M., Ligi C., Kohan C., Dmigan D., Havill N.L. (2006). Lack of association between the increased incidence of Clostridim difficile-associated disease and the increasing se of alcohol-based hand rbs. Infect Control Hosp Epidemiol, 27(5), Bendgens L., Brensing J., Matthes M., et al. (2014). Administration of proton pmp inhibitors in critically ill patients is associated with increased risk of developing Clostridim difficile-associated diarrhea. J Crit Care, 696, e Carling P. (2013). Methods for assessing the adeqacy of practice and improving room disinfection. Am J Infect Control, 41, S Carrico, R. M., Rebmann, T., English, J. F., Mackey, J. Cronin, S. N. (2008). Infection prevention and control competencies for hospital based healthcare personnel. Am J Infect Control, 36; Chang H.T., Krezolek D., Johnson S., Parada J.P., Evans C.T., Gerding D.N. (2007). Onset of symptoms and time to diagnosis of Clostridim difficile-associated disease following discharge from an acte care hospital. Infect Control Hosp Epidemiol, 28(8), Cimiotti J.P., Aiken L.H., Sloane D.M., W E.S. (2012). Nrse staffing brnot, and health care associated infection. Am J Infect Control, 40(6), References Dancer S.J., Kirkpatrick P., Corcoran D.S., Christison F., Farmer D., Robertson C. (2013). Approaching zero: temporal effects of a restrictive antibiotic policy on hospital-acqired Clostridim difficile, extended-spectrm β-lactamase-prodcing coliforms and methicillin-resistant Staphylococcs ares. Int J Antimicrob Agents, 41(2), DeBono, S., Heling, G., Borg, M. A. (2014). Organizational cltre and its implications for infection prevention and control in healthcare settings. J Hosp Infect, 86; 1-6. Dbberke E.R., Carling P., Carrico, R., et al. (2014). Strategies to Prevent Clostridim difficile Infections in Acte Care Hospitals: 2014 Update. Infect Control Hosp Epidemiol, 35(6), Dbberke E.R. & Olsen M.A. (2012). Brden of Clostridim difficile on the Healthcare System. Clin Infect Dis, 55, S Dbberke E.R., Reske K.A., Noble-Wang J., et al. (2007). Prevalence of Clostridim dfficile environmental contamination and strain variability in mltiple health care facilities. Am J Infect Control, 35, Gonzalez E., Nandy P., Lcas A.D., Hitchins V.M. (2015). Ability of cleaning-disinfecting wipes to remove bacteria from medical device srfaces. Am J Infect Control, 43,

18 References Gold C.V., Edwards J.R., Cohen J., et al. (2013). Effect of ncleic acid amplification testing on poplation-based incidence rates of Clostridim difficile infection. Clin Infect Dis,, 57, Griffiths P., Renz A., Hghes J., Rafferty A.M. (2009). Impact of organization and management factors on infection control in hospitals: a scoping review. J Hosp Epidemiol, 73, Gdnadottir U., Fritz J., Zerbel S. (2013). Redcing healthcare associated infections: Patients want to be engaged and learn abot infection prevention. Am J Infect Control, 41(11), Gidance to providers: Testing for C. difficile infection. Vanderbilt University Medical Center Web site. FINAL% pdf Pblished Agst 31, Accessed Febrary 24, Gideline for disinfection and sterilization in healthcare facilities, Centers for Disease Control and Prevention Web site. Updated December 29, Accessed Febrary 24, Gidelines for Environmental Infection Control in Health Care Facilities, Centers for Disease Control and Prevention Web site. Updated May 1, Accessed Febrary 24, References HCUP Projections: Clostridim difficile Hospitalizations 2001 to HCUP Web site. Pblished April 9, Accessed Febrary 24, Hensgens M.P., Goorhis A., Dekkers O.M., Kiiper E.J. (2012). Time interval of increased risk for Clostridim difficile infection after exposre to antibiotics. J Antimicrob Chemother, 67(3), Howell R., Novack V., Grgrich P., Soilliard D., Novack L., Pencina M., Talmor D. (2010). Iatrogenic gastric acid sppression and the risk of nosocomial Clostridim difficile infection. Arch Int Med, 170(9), Hs J., Abad C., Dinh M., Safdar N. (2010). Prevention of endemic healthcare-associated Clostridim difficile infection: reviewing the evidence. Am J Gastroenterol, 105(11), Impact of Antibiotic Stewardship Programs on Clostridim difficile (C. diff) infections. Centers for Disease Control and Prevention Web site. Updated May 13, Accessed Febrary 24, Isaacson D., Haller B., Leslie H., Roemer M., Winston L. (2015). Novel handwashes are sperior to soap and water in removal of Clostridim difficile spores from the hands. Am J Infect Control, 43,

19 References Johnson S., Gerding D.N., Olson M.M., Weiler M.D., Clabots C.R., Peterson L.R. (1990). Prospective, controlled stdy of vinyl glove se to interrpt Clostridim difficile nosocomial transmission. Am J Med, 88(2), Kombj M., Sheahan A., Sn J., et al. (2016) Transmission of Clostridim Difficile dring hospitalization for allogenic stem cell transplant. Infect Control Hosp Epidemiol, 37, Kfelnicka, A. M., Kim, T. J. (2011). Effective tilization of evolving methods for laboratory diagnosis of Clostridim difficile infection. Clin Infect Dis, 52; Kndrap, S., Snkesla, V., Jry, I., Deshpande, A., Donskey, C. (2014). A randomized trial of soap and water hand wash verss alcohol hand rb for removal of Clostridim difficile spores from hands of patients. Infect Control Hosp Epidemiol, 35; Lessa F., M Y., Bamberg W., Beldavs Z.G., et al. (2015). Brden of Clostridim difficile Infection in the United States. N Engl J Med, 372 (9), Linney S., Fernandes T., Einarson T., Sengar A. Walker J.H., Mills A. (2010). Association between se of proton pmp inhibitors and a Clostridim difficile-associated disease otbreak: case-control stdy. The Canadian Jornal of Hospital Pharmacy, 63(1), Litvin M., Reske K.A., Mayfield J., et al. (2009). Identification of a psedo-otbreak of Clostridim difficile Infection (CDI) and the effect of repeated testing, sensitivity, and specificity on perceived prevalence of CDI. Infect Control Hosp Epidemiol, 30, References Magill S.S, Edwards J.R., Bamberg W., et al. Emerging Infections Program Healthcare-Associated Infections and Antimicrobial Use Prevalence Srvey Team. (2014). Mlti State Point-Prevalence Srvey of Health Care Associated Infections. N Eng J Med, 370, Mayfield J.L., Leet T., Miller J., Mndy L.M. (2003). Environmental control to redce transmission of Clostridim difficile. Clin Infect Dis, 31(4), McDonald L.C., Killgore G.E., Thompson A., et al. (2005). An epidemic, toxin gene variant strain of Clostridim difficile. N Eng JMed, 353(23), McGkin M. & Govednik J. (2013) Patient empowerment and hand hygiene. J Hosp Infect, 84, Moore G., Smyth D., Singleton J., Wilson P. (2010). The se of adenosine triphosphate biolminescence to assess the efficacy of a modified cleaning program implemented within an intensive care setting. Am J Infect Control, 38, Mlvey D., Redding P., Robertson C., Woodall C., Kingsmore P., Bedwell D., Dancer S.J. (2011). Finding a benchmark for monitoring hospital cleanliness. J Hosp Infect, 77, Options for evalating environmental cleaning. Centers for Disease Control and Prevention Web site. Pblished December Updated Agst 14, Accessed Febrary 24, Orenstein, R., Aronhalt, K., McMans, J. E. Fedraw, L. A. (2011). A targeted strategy to wipe ot Clostridim difficile. Infect Control Hosp Epidemiol, 32;

20 References Oghton M.T., Loo V.G., Dendkri N., Fenn S., Libman M.D. (2009). Hand hygiene with soap and water is sperior to alcohol rb and antiseptic wipes for removal of Clostridim difficile. Infect Control Hosp Epidemiol, 30(10), Pepin J., Saheb N.B., Colombe M.A. et al. (2005). The emergence of floroqinolones as the predominant risk factor for Clostridim difficile-associated diarrhea: A cohort stdy dring an epidemic in Qebec. Clin Infect Dis, 41(9), Peterson L.R., Robicsek A. (2009). Does my patient have Clostridim difficile infection? Ann Int Med, 151(3), Pincock T., Bernstein P., Warthman S., Holst E. (2012). Bndling hand hygiene interventions and measrement to decrease healthcare associated infections. Am J Infect Control, 40, S Planche T., Aghaiz A., Holliman R. et al. (2008). Diagnosis of Clostricim difficle infection by toxin detection: a systematic review. Lancet Infect Dis, 8, Riggs M.M., Sethi A.K., Zabarsky T.F., Eckstein E.C., Jmp R.L., Donskey C.J. (2007).Asymptomatic carriers are a potential sorce for transmission of epidemic and non-epidemic Clostridim difficile strains among long-term care facility residents. Clin Infect Dis, 45(8), Rtala W.A., Gergen M.F., Weber, D.J. (2012). Efficacy of different cleaning and disinfection methods against Clostridim difficile spores: importance of physical removal verss sporicidal inactivation. Infect Control Hosp Epidemiol, 33(12), See I., M Y., Cohen J., Beldavs Z.G. et al. (2014). NAP1 strain type Clostridim difficile Infection. Clin Infect Dis, 58(10), predicts otcomes from 39 References Sethi A.K., Al-Nassir W.N., Nerandzic M.M., Boblsky G.S., Donskey C.J. (2010). Persistence of skin contamination and environmental shedding of Clostridim difficile dring and after treatment of C. difficile infection. Infect Control Hosp Epidemiol, 31(1), Shama G. & Malik D.J. (2013). Uses and abses of rapid biolminescence based ATP assays. Hyg Environ Health, 216, Int J Shaghnessy M.K., Micielli R.L., DePestel D.D. Arndt J., Strachan C.L., Welch K.B., Chenoweth C.E. (2011). Evalation of hospital room assignment and acqisition of Clostridm difficile infection Infect Control Hosp Epidemiol, 32, Sinkowitz-Cochran R.L., Brkitt K.H., Cerdon T., et al.(2012). The associations between organizational cltre and knowledge, attitdes, and practices in a mlticenter Veterans Affairs qality improvement initiative to prevent methicillin-resistant Staphylococcs ares. Am J Infect Control, 40, Sinkowitz-Cochran R.L., Garcia-Williams A., Hackbarth A.D., et al. (2012). Evalation of organizational cltre among different levels of healthcare staff participating in the Institte for Healthcare Improvement's 100,000 Lives Campaign. Infect Control Hosp Epidemiol, 33, Sitzlar, B., Deshpande, A., Fertelli, D., Kndrap, S., Sethi, A., Donskey, C. (2013). An environmental disinfection odyssey: Evalating of seqential interventions to improve disinfection of Clostridim difficile isolation rooms. Infect Control Hosp Epidemiol, 34; Slayton R.B., Toth D., Lee B.Y. et al. (2015). Vital Signs: Estimated Effects of a Coordinated Approach for Action to Redce Antibiotic-Resistant Infections in Health Care Facilities - United States. Morb Mort Week Rep, 64 (30),

21 References Stabler R.A., Dawson L.F., Pha L.T., Wren B.W. (2008). Comparative analysis of BI/NAP1/027 hypervirlent strains reveals novel toxin B-encoding gene (tcdb) seqences. J Med Micro, 57(6), Stevens, V., Dmyati, G., Brown, J., van Wijngaarden, E. (2011). Differential risk of Clostridim difficile infection with proton pmp inhibitor se by level of antibiotic exposre. Pharmacoepidemiologic Drg Safety, 20; Snenshine R.H. & McDonald L.C. (2006). Clostridim difficile-associated disease: new challenges from an established pathogen. Cleve Clin J Med, 73(2), Valiqette L., Cossette B., Garant M., Diab H., Pepin J. (2007). Impact of a redction in the se of highrisk antibiotics on the corse of an epidemic of Clostridim difficile associated disease cased by the hypervirlent ANP1/027 strain. Clin Infect Dis, 45, S Warny M., Pepin J., Fang A., et al. (2005). Toxin prodction by and emerging strain of Clostridim difficile associated with otbreaks of severe disease in North America and Erope. The Lancet, 366(9491), Weber D. & Rtala W. (2011). The role of the environment in transmission of Clostridim difficile transmission in healthcare facilities. Infect Control Hosp Epidemiol, 32, Wilcox M.H., Fawley W.N., Wigglesworth N., Parnell P., Verity P., Freeman J. (2003). Comparison of the effect of detergent verss hypochlorite cleaning on environmental contamination and incidence of Clostridim difficile infection. J Hosp Infect, 54(2),