1. Containing CRE spread Jon Otter, PhD FRCPath Scientific Director, Healthcare, Bioquell Research Fellow, King’s College London jonathan.otter@kcl.ac.uk www.micro-blog.info @jonotter

3. Contents  What’s the problem?  A brief overview of CRE including an update on the current spread in the US, UK and elsewhere  Sizing the threat to EU countries and elsewhere  Infection prevention and control challenges and strategies

4. What’s the problem? Resistance

5. EnterobacteriaceaeNon fermenters OrganismAmpC / ESBLCPEA. baumannii Attributable mortality Moderate Massive (>50%) Minimal Shorr et al. Crit Care Med 2009;37:1463-1469. Patel et al. Iinfect Control Hosp Epidemiol 2008;29:1099-1106. Falagas et al. Emerg Infect Dis 2014;20:1170-1175. What’s the problem? Mortality

6. What’s the problem? Rapid spread Rapid spread Clonal expansion GI carriage Horizontal gene transfer

7. Understanding the enemy PathogenCRE 1 MRSAVREC. difficile Resistance++++++/- Resistance genesMultipleSingle n/a SpeciesMultipleSingle HA vs CAHA & CAHA At-risk ptsAllUnwell Old DecolonisationNoYesNo Virulence++++++/-+ Environment+/-++++++ 1.Carbapenem-resistant Enterobacteriaceae.

8. NHSN / NNIS data; MMWR 2013;62:165-170. CRE in the USA

9. Invasive carbapenem-resistant K. pneumoniae i.e. CRE (EARS-Net)

10. Invasive multidrug-resistant K. pneumoniae (EARS-Net)

11. Emergence of CRE in the UK PHE ARMRL, 24/01/14 Courtosy of Dr Neil Woodford

12. Available guidelines (not exhaustive list!) UK CRE ToolkitUS CRE ToolkitESCMID Guidelines

13. CRE prevention & control Hand hygiene Cleaning / disinfection SDD? Topical CHX? Education? Contact precautions / single room Active screening Antibiotic stewardship Tacconelli et al. Clin Microbiol Infect 2014;20 Suppl 1:1-55

14. CRE toolkits in the US and UK compared Insert comparison table US ToolkitUK Tookit Isolation Contact precautions, confirmed casesRecommended Preemptive contact precautionsSuggestedRecommended Contact precautions for duration of stayNo recommendationRecommended Screening Screen ‘high risk’ patients on admissionSuggestedRecommended Point prevalence on high risk unitsRecommendedSuggested Contact screeningRecommended Screen staff / household contactsNo recommendationNot recommended Other ‘Enhanced’ infection control measuresRecommended Enhanced disinfectionNo recommendationRecommended Cohort patients and staffSuggestedRecommended Flag patient record & inform receiving facilitiesRecommended Tiered local approachRecommended Develop action plan, education of all staffRecommended Implement antimicrobial stewardshipRecommended Topical decolonisation during outbreaksSuggested

15. Curran & Otter. J Infect Prevent 2014;15:193-198.  Standardise standard precautions.  Avoid an ‘acronym minefield’.  Simple outbreak epidemiology.  Guideline writing dream team.  “Road-test” guidelines.

16. Who do I screen? PHE CPE Toolkit PHE CPE Toolkit screening triggers: a)an inpatient in a hospital abroad, or b)an inpatient in a UK hospital which has problems with spread of CPE (if known), or c)a ‘previously’ positive case. Also consider screening admissions to high-risk units such as ICU, and patients who live overseas.

17. You have positive case: now what? ‘Contact precautions’ Single room+glove/gown Consider staff cohort Contact tracing Trigger for screening contacts or whole unit? Flagging Patient notes flagged Receiving unit informed Education Staff Patient / visitor Cleaning / disinfection Use bleach or H 2 O 2 vapor at discharge Decolonization? ‘Selective decontamination’ / chlorhexidine bathing?

18. Single room isolation: Bioquell Pod

19. Bioquell Pod  Bespoke, semi- permanent  Infectious patients  Privacy & dignity  Reduce forced transfer  Observation & single room

20. The challenge of endoscopes  Cluster of 39 cases of NDM-producing CRE linked to contaminated duodenoscopes. 1  No failures in endoscope reprocessing identified, yet outbreak strain cultured from reprocessed endoscope.  Prompted calls for more sterilization rather than high-level disinfection of endoscopes. 2 1.Epstein et al. JAMA 2014;312:1447-1455. 2.Rutala & Weber. JAMA 2014;312:1405-1406. Meticulously cleaning duodenoscopes prior to high-level disinfection should reduce the risk of transmitting infection, but may not entirely eliminate it. (FDA Feb 23 2015).FDA Feb 23 2015

21. Barriers Carbapenem usageSingle rooms ICD staffing ECDC Point Prevalence Survey, 2013. Debt

22. Cataldo et al. ECCMID 2014. 0125. Typen studiesFailure rateOdds ratio Bundled intervention7528% 1.9 Single intervention1145%

23. What works? Israel Schwaber et al. Clin Infect Dis 2011;52:848-855. * Physical segregation of CRE carriers; cohorted staff; appointed taskforce. *

24. Conclusions  This is a new an evolving problem  Recognition of patient carriers is vital  Appropriate management of identified carriers is crucial  Information may change in time if we see more cases in the EU / US  Important to try and stay up to date and carry on with safe infection prevention precautions…

25. Acknowledgements  Pat Cattini for some of the slides  Image credits: –‘Cotton swabs’ by Jan Gottwei ßJan Gottwei ß

26. Resources  CDC CRE Toolkit CDC CRE Toolkit  AHRQ CRE Tookit AHRQ CRE Tookit  UK Public Health England CPE Tookit UK Public Health England CPE Tookit  Bioquell CRE resources Bioquell CRE resources  UK ESBL guidelines UK ESBL guidelines  ECDC risk assessment on the spread of spreading (CPE) ECDC risk assessment on the spread of spreading (CPE)  Canadian guidelines for carbapenem resistant GNB Canadian guidelines for carbapenem resistant GNB  Australian recommendations for CRE control Australian recommendations for CRE control  ESCMID MDR-GNR control guidelines ESCMID MDR-GNR control guidelines  Webinar on CRE infection control challenges Webinar on CRE infection control challenges

27. Increased risk; prior room occupant Otter et al. Am J Infect Control 2013;41(5 Suppl):S6-11. +71% +58% +55% +49% +42% +37% +28%

28. CRE – is surface contamination a risk? Havill et al. Infect Control Hosp Epidemiol 2014;35:445-447. Error bars represent plus one standard deviation of the mean.

29. Conclusion CRE surface contamination Lerner et al. J Clin Microbiol 2013;51:177-1781.  An Israeli hospital investigated CRE environmental contamination in the vicinity of 34 CRE-carriers; mainly K. pneumoniae.  CRE was detected in the surrounding environment of most (88%) of the patients sampled.

30. Conclusion  K. pneumoniae seems to be more environmental than E. coli. 1,2  Surface contamination on five standardized sites surrounding patients infected or colonized with ESBL-producing Klebsiella spp. (n=48) or ESBL-producing E. coli (n=46). 1 K. pneumoniae vs. E. coli 1.Guet-Revillet et al. Am J Infect Control 2012;40:845-848. 2.Gbaguidi-Haore. Am J Infect Cont 2013 in press. P<0.001

31. Enterobacteriaceae “less environmental” Nseir et al. Clin Microbiol Infect 2011;17:1201-1208. Ajao et al. Infect Control Hosp Epidemiol 2013;34:453-458.

32. Terminal decontamination using HPV Patients admitted to rooms decontaminated using HPV were 64% less likely to acquire any MDRO (incidence rate ratio [IRR]=0.36, CI=0.19-0.70, p<0.001) Passaretti et al. Clin Infect Dis 2013;56:27-35.

33.  Eradication of Serratia from a NICU in Sheffield. 1  Eradication of Acinetobacter and Enterobacter from an ICU in Holland. 2  Terminal disinfection of patient rooms and cohort areas during outbreaks of CRE at Howard County Hospital 3 and the NIH hospital. 4 Control of Gram-negative outbreaks using HPV 1.Bates & Pearse. J Hosp Infect 2005;61:364-366. 2.Otter et al. Am J Infect Control 2010;38:754-756. 3.Gopinath et al. Infect Control Hosp Epidemiol 2013;34:99-100. 4.Snitkin et al. Sci Transl Med 2012;4:148ra116. 5.Donegan et al. SHEA 2010. 6.Kaiser et al. IDSA 2011.