Controversi sies s and Current I Issu ssues s in D Diagnosi - PowerPoint PPT Presentation

Controversi sies s and Current I Issu ssues s in D Diagnosi sis, Survei eillan ance, an and T Trea eatmen ent o of Clo lostrid ridiu ium dif iffic icile ile in infecit iton L. C Clif lifford M McDonald ld, MD Senior Advisor for S cience and Integrity September 16, 2015 Division of Healthcare Quality Promotion National Center for Emerging and Zoonotic Infectious Diseases

No Financial Disclosures The findings and conclusions in this presentation are those of the author and do not necessarily represent the official position of the Centers for Disease Control and P revention.

Clo lostrid ridiu ium d dif iffic icile ile Infect ection (CDI)  Anaer aerobic b bac acter erium  Not n normal al i intes estinal al bac acter erium  Fec ecal al-oral al s spread ead  Forms sp s spores s that persi sist st  Toxin ins produce c colit litis is  Diarrhea  More severe disease, death  2-st steps t s to i infection  Antibiotics result in vulnerability  New acquisition via transmission Figure courtesy of D. Gerding and S . Johnson

Controver ersies es an and C Curren ent Issues es  Are C e CDI rates es beg eginning to d dec ecreas ease? e?  How s sho houl uld CDI b be diagno gnosed?  What is t the r e role o e of as asymptomatic c car arrier ers in transm smissi ssion?  How lo long s should ld p patie ients wit ith C CDI be is isola lated?  Is ther ere t e tran ansmission in o outpatien ent heal ealthcar are e set ettings?

Dischar arges es (primar ary an and s sec econdar ary) Coded ed f for Clo lostrid idiu ium d dif iffic icile ile infec ection ( (CDI), United ed S States es 12 10 CDI Discharges / 1,000 Discharges 8 6 4 2 0 HCUPnet, Healthcare Cost and Utilization Project. Agency for Healthcare R esearch and Quality, R ockville, MD. http://hcupnet.ahrq.gov/

Hospital-Onset C CDI La LabID Events: The N e NHSN Bas asel eline Bas asel eline 2 e 2010-2011 2011 F acilities reporting 846 S tates represented 40 (5 with mandates) F acility quarters 5,086 F acility-wide patient days 62,262,776 F acility-wide admissions 13,102,078 HO-CDI LabID events 45,323

NHSN CDI R Risk Adjusted S SIR A Accou ount nts for or Mor ore Sen ensitive e Tes esting an and P Preval alen ence o e on Admission Var ariab ables es from Final al Model el to be e included ed Data Sources a s and Submissi ssion for Ris isk A Adjustment in in S SIR Calc lcula latio ion Fa Factor Descrip iptio ion • CDI test type, facility bed size, and Intercept teaching type are collected on the required Annual F acility S urvey. F acility Bed S ize > 245 101-245 • The survey is completed after the ≤ 100 end of each year for accuracy in describing a full year’s worth of data. T eaching Type Major Graduate • S urvey data for 2012 will be submitted Limited & Non by facilities January - March 2013. CDI T est Type NAAT (PCR ) • Due to reporting requirements from E IA CMS , quarterly data are complete All Other 4.5 months after the end of each quarter. Prevalence Continuous (no CO-HCF A)

HO HO-CD CDI La LabID Even ents Pred edictive e Model el (2 (2) Par aram amet eter er Effect p-val alue Estimate Inter ercep ept -7.8983 <0.0001 CD CDI Test Ty Type (NAAT v vs. n non-NAA AAT/EIA o A others) 0.3850 <0.0001 CD CDI Test Ty Type (EIA v vs. n non-NAA AAT/EIA o A others) 0.1606 0.0013 Preval alen ence r e rate e (continuous)* 0.3338 <0.0001 ize (>245 vs. ≤ 100) Facilit ility Bedsiz 100) 0.2164 <0.0001 245 vs. ≤ 100) Facilit ility Bedsiz ize (101-245 v 100) 0.0935 0.0022 Medic ical l School l Affilia iliatio ion ( (Major r teachin ing vs. 0.1870 <0.0001 Under ergrad aduate/ e/Non-Teachi hing) ng) Medic ical l School l Affilia iliatio ion ( (Graduate vs. 0.0918 0.0038 Under ergrad aduate/ e/Non-Teachi hing) ng) *Number of community-onset CDI LabID events X 100 Number of admissions to the facility

Relative Sensitivity of C. difficile Tests Culture + Toxin Confirmation > NAAT (RT-PCR, LAMP) > GDH EIA > Cell Cytotoxin > Toxin A & B EIA > Toxin A EIA > GDH Latex Test > Endoscopy

Under erstan anding Pred edictive e Val alue e for Diagnosi sis o s of Dise sease se - T Planche et al. Lancet Infect Dis 8: 777–84, 2008

Is CDI Testing a Function of Clinical Probability of CDI? • If labs have no clinical input and accept all unformed stools for testing, it may be most appropriate to use a test that better identifies likely CDI, such as highly sensitive test for toxin in stool, but we lack proof for this. • If patients are screened carefully for clinical symptoms likely associated with CDI (at least 3 loose or unformed stools in 24h or less with history of antibiotic exposure?), then a sensitive test such as NAAT or toxigenic culture, or GDH+toxin detection may be best.

Asymptomatic Car arrier ers Equal al o or E Exceed eed C CDI Cas ases es an and Increas ease e with Heal ealthcar are e Exposure Loo VG et al. N E ngl J Med 2011;365:1693-703.

Point P Preval alen ence E e Estimates es of Asymptomatic C. dif iffic icile ile Coloni nization n Dur uring H ng Healthc hcare  Loo VG et et al al. : : 4 4.4% as asymptomatic car arrier ers, ~1.8% CDI  Eyre D e DW et et al al. : 11% ( (~5% on ad admission?)  Leek eekha S et et al al.: 9.7% on ad admission  Alas asmar ari F et et al al.: 15% o on ad admission  Riggs M s MM e et a al.: 5 51% cross ss-section nur n nursing ho ng home  Mar arciniak ak C et et al al.: 1 16% o on ad admission to r reh ehab ab  Du Dumford DM et et al al.: 5 50% c cross-sec ection spinal al cord w war ard Loo VG, et al. N E ngl J Med 2011;365:1693-703. E yre DW, et al. PlosONE 8(11): e78445 LeekhaS et al. A J of Infect Contrl 41 (2013) 390-3 Alasmari F et al. Clin Infect Dis 2014;59(2):216–22 R iggs MM et al. Clin Infect Dis 2007;45:992-8 Marciniak et al. Arch PhysMed R ehabil 2006; 87: 2086-9 Dumford DM et al. J S pinal Cord Med 2011; 34(1): 22-7

Inc ncreasing ng Recogni gnition n of Asymptomatic Carriers as as a S a Source f e for C. d dif iffic icile ile Transm smissi ssion  Eyre et e et al al.  E nzyme immunoassay for CDI diagnosis  Only 38% of new cases linked to a symptomatic (CDI) source  Curry et et al al.  Cell cytotoxin neutralization assay for diagnosis  At least 29% of new cases linked to an asymptomatic source  As b better i infection on c cont ontrol ol cont ontains transmission on from om symp mptoma matic ( (CDI) s source, asymp mptoma matic ( (and mi mildly symptomatic ic) p patie ients p pla lay a la larger r role le in in transm smissi ssion  The sensit itiv ivit ity of a a d dia iagnostic ic im impacts in infectio ion c control Curry S R et al. Clin Infect Dis 2013; 57:1094–102. E yre DW et al. N E ngl J Med 2013;369:1195-205.

Infectio ion Control l Implic licatio ions of Dia iagnostic ic and Ther erap apeu eutic Approac aches es  Asymptomatic car arriag age i e increas eases es w with heal ealthcar are an e and especia ially lly a antib ibio iotic ic exposures in in la later lif life  Asy symptomatic c carriage contributes t s to transm smissi ssion  E ven mild diarrhea and incontinence may promote spread  Infection on cont ontrol ol and t treatment nt d decision ons current ntly linked ed b bas ased ed on d diag agnosis of C CDI  Use of more sensitive diagnostics may reduce transmission but also lead to unnecessary treatment  Trea eatmen ents that red educe e the e duration an and d deg egree o ee of asympt ptomatic s sheddi dding c could d have adde dded be d benefit f for reduced t transm smissi ssion

Patien ents C Commonly Rem emai ain C Colonized ed After er Trea eatmen ent of C CDI Abujamel T et al. PLoSOne. 2013 Oct 2;8(10):e76269

Degree of I Intestin inal l Colo loniz izatio ion is is a L Lik ikely ly Det eter erminan ant o of Contag agiousnes ess Donskey CJ et al. J Clin Microbiol 52(1):315; 2013

Chitnis et al. JAMA Intern Med. 2013;173(14):1359 -1367

Jury LA et al. PLoS ONE 8(7): e70175.

Jury LA et al. PLoS ONE 8(7): e70175.

Medication n Use i in C n Communi unity-asso ssociated C CDI, 2009 2009-2011 2011 Most common reasons for antibiotics: upper respiratory and dental procedures Chitnis et al. JAMA Intern Med. 2013;173(14):1359-1367

For or M Mor ore Infor ormation on Clif liff M McDonald ld cmcd cdonald1@ cdc. cd c.gov For m more information please contact Centers f for D Disease C Control and P Prevention 1600 Clifton R oad NE , Atlanta, GA 30333 T elephone, 1-800-CDC-INFO (232-4636)/TTY: 1-888-232-6348 E -mail: cdcinfo@ cdc.gov Web: www.cdc.gov The findingsand conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. National Center for E merging and Zoonotic Infectious Diseases Division of Healthcare Quality Promotion