OAHHS Webinar Christopher D. Pfeiffer, MD, MHS April 30, 2014
Learning Objectives / Outline 1. Understand: What are CRE? Which CRE are most important? Why? 2. Learn about CRE epidemiology, nationally and locally. 3. Understand how are we are approaching CRE prevention and control in Oregon, and think about your facility s role in this effort.
Case A 63 y.o. Indian female is transferred from a hospital in India for treatment of end-stage lung disease per her son s request. She arrives intubated/sedated. She arrives with sparse transfer documents. Hospital Day 2: septic shock. Antibiotics are initiated (vancomycin/pipercillin-tazobactam). 12 hours later, blood cultures are positive.
Antibiogram (example) Resistant Susceptible Yong et al. Antimicrob Agents Chemo 2009:5046-5054
Case, continued NDM-1 CRE was identified The patient died This is typical: mortality 30-50% of patients with invasive CRE infection Infection control notifies administration of a superbug problem.
http://www.cdc.gov/drugresistance/threat-report-2013/ Accessed October 5, 2013
http://www.pbs.org/wgbh/pages/ frontline/hunting-the-nightmare-bacteria/
Frontline: 3 stories 11 yo F with MRSA bacteremia, complicated by pan-resistant Stenotrophomonas pneumonia. Survived after undergoing lung transplant 19 yo M with traumatic injury in Calcutta complicated by NDM-1 CRE infection, treated in Seattle and survived (amputation, many surgeries) NIH KPC CRE outbreak: 18 patients infected or colonized 6 deaths (33%) due to the infection
CRE: Huge Clinical Impact 30-50% mortality of CRE infection across multiple studies Common CRE infections include: Bacteremia Pneumonia UTI/urosepsis abdominal abscess Patel et al. ICHE 2008;29:1099-1106
Background: What exactly are CRE?
Multidrug-Resistant Gram Negative Bacilli (MDR-GNB) Pseudomonas aeruginosa Acinetobacter baumannii MDR-Enterobacteriaceae Enterobacteriaceae a family of gut bacteria including: E. coli, Klebsiella spp., and Enterobacter spp. Their drug resistance is not species-specific so they are better known by their resistance mechanisms. ESBLs, AMPCs, CREs
Enterobacteriaceae: Resistance Mechanisms Drug Class Examples Resistance Mechanism β-lactams Penicillin, Amoxicillin β-lactamases Β-lactam/ β-lactamase inhibitors Cephalosporins Carbapenems Amoxicillin-clavulanic acid (Augmentin) Cephalexin (Keflex) Ceftriaxone (Rocephin) Cefepime (Maxipime) Ertapenem (Invanz) Imipenem (Primaxin) Meropenem (Merrem) Doripenem (Doribax) Extended-spectrum β- lactamases (ESBLs) Extended spectrum cephalosporinases (e.g., AmpC) Carbapenemases
What are CRE? CRE are Enterobacteriaceae which test resistant to carbapenem antibiotics. However, it s complex: CRE is a very heterogeneous group of organisms Certain CRE have spread rapidly worldwide and are associated with highly lethal outbreaks; others are not.
Types of CRE 1. Carbapenemase-producing Enzymes produced by bacteria which directly inactivate carbapenem antibiotics (e.g., KPC, NDM, OXA-48, VIM, IMP) Rapid worldwide spread!!! Uncommon in Oregon 2. Non-Carbapenemase-producing Multiple resistance mechanisms combine to confer carbapenem resistance (e.g., AMPC + porin mutation) Stable incidence over 20 years Relatively common in Oregon
CRE Assessment Tiers* Tier Description Recommended Action (acute care facilities) 1 Carbapenemase-producing CRE (CP-CRE) Most aggressive control measures 2 CRE with acquired resistance NOT due to carbapenemase production Control measures as for other MDRO infections *see Oregon CRE Toolkit 2013
Oregon CRE Definition (2014) Non-susceptible (i.e., intermediate or resistant) to 1of the following carbapenems: doripenem, imipenem, or meropenem AND resistant to all of the 3 rd generation cephalosporins tested: cefotaxime, ceftriaxone, and/or ceftazadime*; OR Carbapenemase-positive by PCR; OR Positive for carbapenemase production by a phenotypic test (e.g., Carba NP or Modified Hodge Test). *For labs using the current CLSI breakpoints
Transmission and Epidemiology of CRE
Global/National Epidemiology Name 1 st Report Worldwide 1 st Report US Current Epidemiology US KPC 2001 North Carolina NDM 2009 Sweden (from India) OXA-48 2004 Turkey IMP 1994 Japan VIM 2002/2003 Greece, Korea, Taiwan 2001 CDC surveillance (NC) 2010 Returned travelers, India 2012 SMART surveillance, unknown location 2011 CA (3 cases/nicu, source unknown) 2010 Returned traveler, Greece Widespread: ~11% of Klebsiella spp. reported to NHSN were carbapenem-r Uncommon: ~49 cases reported to CDC (July 1) Rare Rare Rare
CDC CRE map (12/31/13) http://www.cdc.gov/hai/organisms/cre/trackingcr E.html accessed Jan 2014
CRE burden by facility type From facilities reporting CRE to NHSN, Jan-June 2012 CAUTI=catheter-associated UTI; CLABSI=central-line-associated bloodstream infection MMWR 2013 Mar 8;62(9):165-170
Note: using the 2014 Oregon CRE definition
Clinical Impact
Why the high mortality? Possibly increased organism fitness and/or virulence Limited treatment options, which typically include: Colistin (toxic to kidneys) Tigecycline (black box warning, death ) Aminoglycoside (toxic to kidneys) Fosfomycin (approved for UTIs only) Some CRE are pan-resistant
Adopted from Alex Kallen,MD, MPH CRE Mortality (typical example) 60 p<0.001 p<0.001 Percent of subjects 50 40 30 20 10 0 Overall Mortality Attributable Mortality OR 3.71 (1.97-7.01) OR 4.5 (2.16-9.35) CRKP CSKP Patel et al. ICHE 2008;29:1099-1106
Antibiotic Pipeline? New systemic antibacterial agents approved by the US Food and Drug Administration per 5-year period, through 2012. Boucher H, et al. Clin Infect Dis 2013;56:1685-94 http://www.idsociety.org/index.aspx, accessed 10/20/13
With few antibiotics coming, antibiotic stewardship is critical!
Review so far Carbapenemase-producing CRE are an urgent threat to public health They are easily transmissible and rapidly spreading CRE cause highly lethal infections CRE are common many places but uncommon in Oregon. So, what are we doing in Oregon to prevent and control CRE?
2 examples we used as templates for our approach to CRE
KPC outbreak, Chicago-area, 2008 Figure: Exposure Network Analysis n=10 n=14 n=2 n=40 Letter = Facility Number = Patient Black = clinical Cx Red = surveillance Cx Arrow = origin of CRE could be determined Line = origin of CRE uncertain Won S. et al. Clin Infect Dis 2011;53:532-40
Regional Control is Critical Although few cases were identified at most institutions, many facilities were affected. Successful control of KPC-producing Enterobacteriaceae will require a coordinated, regional effort among acute and long-term health care facilities and public health departments. Won S. et al. Clin Infect Dis 2011;53:532-40
CRE Outbreak, Israel 2005: KPC introduced to Israel 2006: multiple outbreaks in hospitals reported 3/2007: the Ministry of Health issued guidelines for country-wide CRE control 4/2007-5/2008: initial intervention period mandatory CRE reporting to public health; mandatory isolation of hospitalized CRE carriers; and creation of a multi-disciplinary task force which paid site visits and supervised adherence to the guidelines Schwaber MJ, et al. Clin Infect Dis 2011;52:848-55
Israeli CRE outbreak control CRE clinical cases, 2005-2008 Schwaber MJ, et al. Clin Infect Dis 2011;52:848-55 CRE acquisition (blue) and bacteremia (red), 2008-2013 Schwaber MJ and Carmeli Y. Clin Infect Dis 2014 advanced access
CRE Prevention and Control in Oregon
The Oregon Drug-Resistant Organism Prevention and Coordinated Regional Epidemiology (DROP-CRE) Network CRE Initiated September 2012
Initial Goals Develop a CRE surveillance and response plan Assess needs and capabilities for MDRO/CRE response Coordinate MDRO/CRE education Develop and disseminate an Oregon-specific CRE Toolkit
DROP-CRE Network Structure Working group: Public health: Oregon HAI program director 2 physicians 1 epidemiologist Academia (OHSU, PVAMC): 2 ID physicians (and hospital epidemiologists) 1 PhD epidemiologist 1 ID fellow Multi-disciplinary Advisory Committee: 22 members
Methods 1. CRE surveillance case definition established 2. CRE database created 3. Laboratory capacity expanded (real-time PCR testing) 4. Self-administered surveys performed: Microbiology lab directors Infection preventionists (IPs) in acute care hospitals IPs in long-term care facilities (LTCFs) 5. Real-time outbreak assistance initiated 6. Working group members lectured statewide 7. Oregon CRE Toolkit published
Real-Time Outbreak Assistance DROP-CRE working group members are available to support the local facility when CRE cases are detected (phone or on-site consultation)
The Oregon CRE Toolkit Published June, 2013 Contains specific recommendations for Oregon facilities. http://public.health.oregon.gov/diseasesconditions/diseasesaz/cre/documents/cre_toolkit.pdf
Oregon CRE Toolkit 1. Overview 2. OHA CRE Definition and CRE Reference Guide 3. Prevention and Control in Acute Care 4. Prevention and Control in Long Term Care 5. Prevention and Control in Ambulatory Care 6. Recommendations for Microbiology Laboratories 7. References 8. Appendices (response diagrams, laboratory protocols, educational material including patient/staff FAQs, environmental cleaning monitoring tool, inter-facility transfer form)
How Can Hospital Administration Help? Support infection control and CRE education Support CRE prevention and control efforts in an early, aggressive response to CRE cases Early efforts will likely mitigate long-term consequences of a larger CRE outbreak. Offer financial support towards control efforts Moneys for screening cultures Additional dedicated F.T.E. may be required for patient and staff cohorting, monitoring of hand hygiene and adherence to contact precautions, etc.
For more information
2 Related Initiatives http://blog.thoughtstream.ca/types-of-collaboration/
New Oregon Regulations require communication of MDROs between health care facilities, Jan. 2014* When a referring health care facility transfers or discharges a patient who is infected or colonized with an MDRO, it must include written notification of the infection or colonization to the receiving facility in transfer documents. *OAR 333-019-005
Regional MDRO Collaboratives CDC-funded grant administered by the Oregon Patient Safety Commission (2013-14) Goal: encourage multidisciplinary, inter-facility collaboration re: best practices related to MDRO prevention and control 3 Oregon regions participating (regional hospitals and long-term care facilities)
DROP-CRE: Future Directions Continue CRE surveillance and education Aggressive infection control response for CRE cases Improve inter-facility communication and regional collaboration Apply lessons learned to focus on other MDROs Create a regional MDRO Toolkit
Summary CRE are an urgent global threat and cases have a high mortality. In Oregon, CRE cases are uncommon: this is UNIQUE opportunity to prevent CRE emergence. Leadership support of infection prevention and control at the facility level is required. A regional approach to CRE control is critical; use the DROP-CRE team as a resource for your facilities.
Current Working Group Zintars Beldavs, MS Gen Buser, MD, MSHP Maureen Cassidy, MT, MPH Ann Thomas, MD, MPH JJ Furuno, PhD John Townes, MD Andy Leitz, MD Mary Post, RN, MS, CNS, CIC Christopher Pfeiffer, MD, MHS Regional Collaborators DROP-CRE Advisory Committee Margaret Cunningham, MPH Tasha Poissant, MPH Robert Arao, MPH Oregon Patient Safety Commission Acknowledgements THANK YOU! National Collaborators Alex Kallen, MD, MPH (CDC) Nimalie Stone, MD (CDC) Keith Kaye, MD, MPH (Detroit Medical Center) Robert Bonomo, MD (Cleveland VAMC) PVAMC and the OHSU ID Division Tom Ward, MD Graeme Forrest, MBBS (and others) Janice Jou, MD, MHS