David R. Lichtenstein, MD, FASGE, AGAF, FACG Director of Endoscopy Boston University Medical Center

Transcription

1 David R. Lichtenstein, MD, FASGE, AGAF, FACG Director of Endoscopy Boston University Medical Center Web:

2 Risk of Transmission of Infection with Duodenoscopes Information obtained from multiple sources. Search of the peer-reviewed medical literature via the United States National Library of Medicine s MEDLINE database Reports from the FDA, CDC, professional medical societies, health care community, news agencies, and personal communication FDA s Manufacturer and User Facility Device Experience database, or MAUDE. This houses medical device reports (MDRs) Submitted by mandatory reporters (manufacturers and user facilities) Voluntary reports such as health care professionals and patients Internet via Google s search engine

3 Infections Traced to Duodenoscopes: Questions For Discussion What is the risk of infection to our patients? What types of infectious agents have been transmitted? What is the mechanism of transmission? How do we handle outbreaks? What should we tell our patients? How can we prevent transmission? Is high level disinfection sufficient? Should we sterilize duodenoscopes? What is being done by professional societies, manufacturers, and governmental agencies (i.e., FDA, and CDC)?

4 Prevention of ERCP Infections: Adequate Reprocessing? Background ~670,000 ERCPs in the U.S. annually Endoscopes heat labile and Spaulding classification of semicritical devices --- therefore undergo HLD Prior to 2013 reprocessing of duodenoscopes reportedly adequate to prevent transmission of infection if done in accordance with manufacturer and Multisociety Guidelines

5 Duodenoscope Infection Transmission: Historical Timeline Cryan et al. (1984) P. aeruginosa Allen et al. (1987) P. aeruginosa Alverado et al. (1991) P. aeruginosa Streulens et al. (1993) P. Aeruginosa and 3 strains of Enterobacteriaceae inadequate HLD of air/water channels *Failure of AER to dry duodenoscope internal channels including elevator wire channel *Faulty design of AER resulting in contamination of water used to rinse after HLD *Improper reprocessing and drying. Resolved with HLD of exposed elevator wire channel and alcohol flushing/drying of all channels * Terminal rinse 70% alcohol f/b forced air dry

6 January 3, 2014 Centers for Disease Control and Prevention (CDC). MMWR Morb Mortal Wkly Rep 2014; 62: 1051 [PMID: ] First and largest U.S. outbreak with CRE (NDM-1 producing carbapenem-resistant E. coli) from a contaminated duodenoscope Occurred at Advocate Lutheran General Hospital (650-bed teaching hospital) in the suburbs of Chicago, IL; United States Incident patient with Alzheimer s disease, failure to thrive underwent ERCP 1/28/13 for GSP with ES, removal of stones, and stent placement followed readmit from skilled nursing home with uncomplicated UTI 3/26/13

7 What are Superbugs and CRE? Superbugs is a moniker used to describe certain epidemiologically important, multidrugresistant organisms (MDRO) Well known superbugs include CRE, VRE and MRSA Carbapenem-Resistant Enterobacteriaceae (CRE): Enterobac. includes > 70 genera and the largest collection of medically important GN bacilli. Many are enteric (e.g., Klebsiella, Salmonella, Enterobacter, Serratia. Not Pseudomonas or Acinetobacter) Resistant to multiple abx and some pan-resistant Inherently sensitive to HLD agents and standard reprocessing Share mobile pieces of genetic material Comorbidities or immunosuppression at greatest risk of infection and death Infections of bloodstream mortalities ~40-50% Penicillin core structure Carbapenem core structure

8 Significance and Types of CRE? According to CDC > 2 million infected with superbug annually in U.S. Types of CRE: KPC (Klebsiella Pneumonia Carbapenemase)-producing Enterobacteriaceae: First case of CRE in the U.S. isolated in North Carolina in 2001 New Delhi metallo-b-lactamase (NDM-1)-producing K pneumoniae: first described in 2009 in a Swedish patient who had undergone medical care in India where this strain is frequently recovered. From , 27 patients infected with NDM-producing CRE in U.S. Since January 2013, additional 69 pts with 44 from the Illinois outbreak VIM (Verona integron-encoded metallo-β-lactamase)-producing Enterobacteriaceae : First identified in Italy. VPKP in U.S. 2010

9 JAMA. 2014;312(14): doi: /jama

10 CRE rectal screening of patients epidemiologically linked to case patients (e.g., roommates from initial hospital or after discharge in long-term care facility) Reprocessing procedures, AERs and duodenoscope function were reviewed by the field team and manufacturers Cultures obtained from. Duodenoscopes (Pentax ED-3490TK) Procedure rooms and reprocessing area JAMA. 2014;312(14): doi: /jama The Investigation (8/2013): CDC, FDA, Illinois DPH, and CMS

11 Field Investigation Field Investigation (January-July 2013) 9 sentinel patients C7 JAMA. 2014;312(14): doi: /jama C8 S28 C S Patient at LGH Patient not at LGH Clinical culture diagnosis Screening culture diagnosis Clinical Cases (September 2013) 2 case patients C1 C2 C3 C4 C5 C6 C9 C10 Duodenoscope A Duodenoscope B Duodenoscope C Duodenoscope A Patient Notification (8/12/2013) 94 notified; 58 screened; 23 cases S1 S5 S9 S13 S17 Duodenoscope B Patient Notification (11/5/2013) 39 notified; 16 screened; 1 case S24 Duodenoscope C Patient Notification (10/4/2013) 23 notified; 15 screened; 3 cases S25 S26 S27 S2 S6 S10 S14 S18 S21 S3 S7 S11 S15 S19 S22 S4 S8 S12 S16 S20 S23 S patient undergoing ERCP during study period notified 156 exposed to duodenoscopes A, B, or C 89 returned for screening rectal swab (30% +) 35 of 39 CRE infected patients exposed to ERCP

12 Cultures from elevator channel of duodenoscope A positive for NDM producing E coli CRKP cultured from same duodenoscope did not infect/colonize patients CDC reported no breaches in reprocessing or scope damage. CMS Enzymatic cleaner and disinfectant not on AER manufacturers list but listed by US FDA as identical to products on list Compatible cleaning brush but not the brand on manufacturer list Complex design issues a challenge to clean elevator mechanism Cables and channel (open to closed design importance?)

13 Clinical Characteristics of NDM-1 Producing E. coli Patients (n=39) Culture site (n=39) No. (%) Rectal screening (colonization) 29 (74%) Clinical cases* (>1 infection/pt) 10 (26%) UTI 1 (2.5%) UTI with sepsis (fatal) 2 (5%) Abdominal wound 2 (2.5%) Abdominal abscess 2 (2.5%) Sputum 2 (5.0%) Blood with sepsis 2 (5%) Catheter tip 2 (5%) *Time from ERCP to clinical infection: mean 30 d, range d

14 Gastrointest Gastrointest Endosc Endosc 2015;81: INDEX PATIENT Milwaukee, Wisconsin, USA. (2013) 57 yr/m from India Non-Hodgkin s lymphoma Autologous stem-cell Tx Febrile illness days later Typhlitis on CT scan Blood culture NDM-1 E coli One month later (May, 2013): Cholangitis ERCP and CBD stone extraction Bile culture NDM-1 E coli (same isolate)

15 Duodenoscope taken out of use (11/13) Cx (-) ---- ETO sterilization 27 pts.offered CRE screen (all 13 tested were negative) Nov August 2013 Investigation (5/2014) Epidemiology Microbiology ID CDC/FDA Gastrointest Endosc 2015;81: *Time to clinical Symptoms: 6 mos, 2 mos, 10 mos * 27 additional pts exposed to same duodenoscope May 2013 Index patient

16 UCLA CRE Outbreak: Reported March, 2015 Source pt Infected patients 7 Patients infected with CRKP Cultures of all duodenoscopes (n=5) negative Repeat culturing per CDC recommendations also negative ATP testing of bioburden all WNL (although 1 scope >> others)

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18 Duodenoscope-Related MDRO Outbreaks Highlands County ( ) Wisconsin (2013) Lutheran General (2013) U of Pitt ( ) VA Mason ( ) Deaths Cases UCLA (2014) Cedars-Sinai (2014) Totals: 7 outbreaks, 70 cases, 23 deaths, 49 colonized

19 Reported MDRO Outbreaks with Duodenoscopes* Institution* (occurrence) Highlands, FL ( ) UPMC, PA ( ) VA Mason ( ) LGH, IL ( ) MCW, WI (2013) UCLA (2014) Cedars Sinai (2014) Pathogens # Patients with clinical infections # Patients exposed/ screened/co lonized # Deaths Duodenoscope (culture) CRKP 7 51/46/3 1 NR (+ NDM-1 E.coli) CRKP 7 NR/68/18 0 Olympus TJF-Q180V (Positive) Hyper-ampC E.coli NDM-1 E.coli NDM-1 E.coli 32 NR/0/NR 16 31d) Olympus160/180 (Positive) 9 226/102/30 2 Pentax ED-3490TK (Positive) 4 NR/27/1 0 Olympus TJF-Q180V (Negative) CRKP 7 179/NR/0 3 Olympus TJF-Q180V (Negative) NDM-1 E.coli 4 71/NR/NR 1 Olympus TJF- Q160V? (Negative) Totals /197/ positive * Additional outbreaks reported to FDA and limited data in news (Pentax ED-3670TK and Fujinon ED-530XT)

20 Detection of Duodenoscope- Likely underrecognized Long-lag time Transmitted Infections Asymptomatic carrier state Organisms native gut flora Scope no longer colonized Epidemiologic concern Clinical infectious outbreaks Severe consequences Unusual organisms Other modes of detection Surveillance cultures of duodenoscopes Screening of patients with possible MDRO exposure for colonization (rectal swab)--- CDC CRE toolkit:

21 Duodenoscope Infection Transmission: It s a Global Problem Kovaleva et al Groningen, Netherlands (2008;2009) Pseudomonas Carbonne et al. Paris, France (2009;2010) CRKP Aumeran et al. Clermont- Ferrand,France ( ;2010)ESBL- KP Verfaille et al. Rotterdam, Netherlands (2012;2015) VIM-2 P. aeruginosa Kola et al Berlin, Germany ( ;2015) CRKP 3 patients multidrug resistant P. aeruginosa Endoscopy, patients infected by single contaminated ERCP scope 16 pts. infected by ESBL-KP (Organism recovered from single duodenoscope) 22 pts. Infected and scope culture positive (1) Scope Autopsy: O-Ring seal 12 pts. Infected Duodenoscope culture negative ESBL-extended-spectrum beta-lactamase

22 Management of Duodenoscope-Related Infections: An Ounce of Prevention Identify contaminated duodenoscopes surveillance Improve reprocessing Identify and eradicate patient reservoir Reduce Infection Modify duodenoscope construction

23 Reassess current reprocessing practices for duodenoscopes Add to informed consent process Implement a comprehensive quality control program Re-educate frontline staff about issues specific to elevator Conduct performance and competency assessments include observation and written exams when hired, at least annually, breaches, and new equipment Multidisciplinary input sought from key facility staff Quality officer Infection control GI endoscopy Risk management staff

24 Enhanced Reprocessing Guidance: FDA (2/19/15), CDC (3/12/15), ASGE (3/17/15) Reprocessing practice should include strict adherence to manufacturers Instructions For Use (IFUs) and Multisociety Guidelines for Reprocessing Each reprocessing step is of importance with emphasis on.. Inspection and manual cleaning process Inspect for visible debris and consider magnification (10x) Meticulously clean elevator mechanism in open and closed positions. Raise and lower elevator throughout cleaning Drying and Storage Channels of the duodenoscope and elevator mechanism thoroughly dried prior to storage (includes alcohol flush followed by forced air drying) Document specific endoscope used for each procedure

25 Precleaning During immersion, raise and lower the elevator three times Manual Cleaning and Manual HLD Additional brushing of the forceps elevator recess area Two different-sized brushes. MAJ-1888 brush added to current brush for further cleaning (deeper access to elevator mechanism) Additional flushing of forceps elevator recess area Additional raising/lowering of the forceps elevator (sides)

26 Virginia Mason MDR E.coli Outbreak Ross AS et al. Gastrointest Endosc 2015;82: ERCPs from November 2012 to August patients with MDR E.coli all post-ercp HAC E.coli cultured from 4 of 8 duodenoscopes 3 of 4 required critical repairs (w/o malfunction) 7 deaths within 31 days; 16 deaths total* HLD with sequestration Post-HLD quarantine until culture negative Increased scope turnaround time From minutes to 2-3 days Very costly (1,500-1,800 ERCPs annually) Increased scope inventory-added 20 duodenoscopes (~$40,000/each) surveillance cultures=$$s * Uncertain contribution with most end-stage malignancy or severe comorbidities

27 Of Greatest Concern: VMMC Quarantined Surveillance Cultures Defect rate for HLD (pathogenic bacteria) was ~2% 2 duodenoscopes >1 repeat cycle of HLD (sent to manufacturer) and 1 culture (+) after multiple cycles taken out of service Bacteria No. Acinetobacter 2 Enterococcus 9 Escherichia coli 4 (HAC, n=2) Enterobacter 1 Pseudomonas aeruginosa 2 Nonfermenting GNRs 3 Staphylococcus aureus (Methicillin sensitive) 7 Staphylococcus aureus (Methicillin resistant) 1 Total 29/1524 = 1.9% HAC, Hyper Amp C Ross AS et al. Gastrointest Endosc 2015;82:477-83

28 Routine Daily Reprocessing: Without Known CRE Risk Reprocessing Practices (+/- linear EUS) Culture and sequestration until confirmed disinfected Double cycles of washing and reprocessing for all endoscopes with elevators HLD f/b ETO (selectively or after each procedure) Review with your hospital infection control staff and administration to determine which approach is most practical and efficacious for your institution Additional testing? ATP (validated for manual not HLD) Hang time testing (after storage) PCR (after HLD and storage)

29 Is it Time to Change from Disinfection to Sterilization? Ethylene Oxide (ETO)-LTGS Not FDA approved but compatible with and manufacturer guidance available Uncertain if can overcome deficiencies in HLD Long processing and aeration time (24 hrs) Toxicity for staff and patients? Instrument durability? Not widely available (offsite) Costly Routinely vs. selectively (patient or scope colonized w/mdro)

30 Reported MDRO Outbreaks with Duodenoscopes Institution (occurrence) Highlands, FL ( ) UPMC, PA ( ) VA Mason ( ) LGH, IL (2013) MCW, WI (2013) UCLA (2014) Cedars Sinai (2014) Pathogens # Patients with clinical infections # Patients exposed/ screened/co lonized # Deaths Duodenoscope (culture) CRKP 7 51/46/3 1 NR (+ NDM-1 E.coli) CRKP 7 NR/68/18 0 Olympus 180 (Positive) HyperampC E.coli NDM-1 E.coli NDM-1 E.coli 32 NR/0/NR 16 (7@31d) Olympus 180 (Positive) 9 226/102/30 2 Pentax ED- 3490TK (Positive) 4 NR/27/1 0 Olympus 180 (Negative) CRKP 7 179/NR/0 3 Olympus 180 (Negative) CRE 4 71/NR/NR 1 Olympus 180 (NR) Totals /197/49 23 Postoutbreak reprocessing protocol* NR ETO HLD and quarantine ETO ETO ETO HLD and quarantine * No breach in reprocessing procedures and no additional infections after new reprocessing protocol

31 Interim Protocol for Duodenoscope Surveillance for Contamination After Reprocessing (CDC ) Routine culturing not part of current U.S. guidelines (unlike European and Australian) Limited information to guide the use of postreprocessing surveillance cultures to assess adequacy outside of recognized outbreak settings Some facilities performing regular monitoring If employed--consider CDC methodology (neutralizer) Instrument channel, elevator mechanism (raised and lowered positions) and distal end of scope Optimal frequency not established (each use vs. interval) Disclaimer-method has not been validated!!

32 CDC Protocol For Duodenoscope Surveillance Cultures Test duodenoscope and consider holding until culture results available Positive Low-concern organisms e.g., coagulase-negative staphylococci, micrococci, diptheroids, Bacillus spp and other gram-positive rods Return to circulation if culture below acceptable quantitative level (facility-specific acceptable levels typically <10CFU/scope) Reprocess to remove PBST before scope use Negative Reprocess again to remove PBST Any high-concern organisms e.g., S. aureus, Enterococcus spp., Streptococcus sp. viridans group, Pseudomonas aeruginosa, Klebsiella spp., Salmonella spp., Shigella spp., and other GNRs Procedure review Reprocess and reculture Return when culture negative or below acceptable level for LCO Consider notification of patients exposed to duodenoscopes since last negative cultures If cultures repeatedly positive (3 or more) for any HCO or significant LCO consider reevaluating culture methods and/or send scope to manufacturer for evaluation

33 Clinical Scenario: Patient with Newly Identified MDRO Following Recent ERCP Culture positive for MDRO/CRE Contact hospital ID & infection control Submit a report to manufacturer and FDA Via Medwatch ( ort/ucm htm) Notify and screen patients exposed (interval prior sequestered) Identify the duodenoscope used in the case(s): Culture and sequester Sequester and treat contaminated scope with ETO sterilization or repeated HLD until absent HCO Culture negative Continue to use

34 Clinical Scenario: ERCP in Patient with Known MDRO Take duodenoscope(s) out of service HLD +/- ETO followed by surveillance culture and continued sequestration Culture positive Culture negative Ready for use

35 Your Unit Survey: Surveyors will ask whether duodenoscopes are present in your facility. If the answer is yes, then surveyors must: Request a copy of the manufacturer s instructions for use (IFU) for the duodenoscope(s) as well as any AERs the facility uses in reprocessing duodenoscopes Observe duodenoscopes being reprocessed Ask the responsible staff to explain and demonstrate how they are adhering to manufacturers instructions and Multisociety Guidance Noncompliance must be cited accordingly

36 Recommendations for Units that Use Duodenoscopes or other Scopes with an Elevator

37 Duodenoscope Superbug Transmission: Historical Timeline U. of Pittsburgh (2014) Hartford (3/2015) Wisconsin (GIE, 2015) Illinois 2015 Highlands, FL (AJIC, 2013) LGH Outbreak MMWR/CDC/ JAMA, 2014 VA Mason (2/2015) UCLA (2/2015) Cedars-Sinai (2/2015) Olympus validated new reprocessing TJF-180V (3/26/15) FDA Safety communication (2/19/15) FDA GI-Urology Devices Committee meeting (5/15/15) CDC Interim Surveillance Protocol 3/12/15) FDA Supplemental Reprocessing Guidance (8/4/15) ASGE Guidance (3/17/15) Custom Ultrasonics AER Recall (11/13/15) FDA Finalizes Reprocessing Guidance (3/17/15) Fujinon updated reprocessing (12/23/15) Fujinon updated reprocessing (3/17/15) Olympus Corrective Action (1/15/16)

38 FDA Safety Communication 12/23/2015 FUJIFILM Medical Systems, U.S.A., Inc. Validates Revised Reprocessing Instructions for Model ED- 530XT Duodenoscopes: FDA Safety Communication

39 Custom Ultrasonics AERs Likely Contributed to Outbreaks November 13, 2015 FDA issued mandatory recall all 2,800 CU AERs CU AERs in 9 of 16 domestic outbreaks (~141 infections) UPMC Presbyterian Hospital, Pittsburgh, PA NYP/Weill Cornell Medical Center, New York City, NY UMass Memorial Hospital, Worchester, MA Advocate Lutheran General Hospital, Park Ridge, IL Hartford Hospital, Hartford, CT Massachusetts General Hospital, Boston, MA UCLA Medical Center, Los Angeles, CA Carolinas Medical Center, Charlotte, NC Thomas Jefferson University Hospital, Philadelphia, PA 10-20% market share of AERs in U.S. Did not validate.. Compatibility with closed-channel duodenoscopes AERs with specific types of HLD cleaning solutions Effectiveness of pre-filters (prevent large particulate contamination) Water filtration system

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41 Additional Outbreaks: Health, Education, Labor, and Pensions (HELP) Committee (Senate Report) Hospital Location Clinical Infections (#) Time of Infections Duodenoscope Manufacturer NY Presbyterian- Weill Cornell New York City 15 December, 2012 U. MA Medical Worcester, MA 20 December, 2012 Olympus Olympus Carolina Medical Charlotte, NC Olympus Jefferson Univ. Hospital Philadelphia, PA 8 January, 2013 Hartford Hospital Hartford, CT 12 January, 2014 Olympus Olympus MGH Boston, MA 7,5, & 2015 Pentax Boca Raton Regional Hospital Boca Raton, FL 9 August, 2014 Olympus Carolinas Medical Charlotte, NC Olympus Allegheny General Pittsburgh, PA 1 February, 2015 Olympus Fox Chase Philadelphia, PA 3 April, 2015 Fujifilm

42 Olympus (with FDA guidance) announce recall of the TJF180v endoscopes Beginning in February all scopes recalled and the elevator system will be replaced with a newer higher tolerance system Recall at no charge to scope owners and started with the scopes that have been in service the longest Olympus will also institute a mandatory yearly inspection of the scope and elevator mechanism at a repair facility

43 Olympus Update New reprocessing manual also issued with changes in pre-cleaning instructions, ETO sterilization cycles and AER disinfectant recommendations. FDA allows current version of the TJF180v scopes to remain in service during recall using the newest reprocessing guidance from Olympus While the new design and reprocessing has been validated it is unclear if this will reduce transmission of CRE or other organisms until extensive clinical use is recorded

44 Take Home Messages Contaminated duodenoscopes are an infrequent but important cause of outbreaks of CRE and other related superbugs Outbreaks observed despite following reprocessing guidelines Infections occur with duodenoscopes from all 3 manufacturers Attributed to persistent contamination at elevator region, cable channels, or both Report issues to MedWatch ( Research needed for improved reprocessing and endoscope design Zero tolerance for duodenoscope transmission of infection