DROP-CRE Network IP Survey andOregon CRE Toolkit Review

Christopher D. Pfeiffer, MD, MHSOSWAPIC Chapter Meeting

April 9, 2013

Learn about the newly established DROP-CRE Network.

Review results of the DROP-CRE Infection Prevention Survey on MDRO practices.

Review the updated Oregon CRE Toolkit with a focus on understanding the Oregon CRE definition and Infection Preventionists’ role in CRE prevention and control.

Learning Objectives

Drug-Resistant Organism Prevention and Coordinated Regional Epidemiology (DROP-CRE) Network

Initiated September 2012

Statewide network to detect, control, and prevent multidrug-resistant organisms

(MDROs)

CRE

Zintars Beldavs, MS (OHA) Genevieve Buser, MD (OHA) Margaret Cunningham, MPH (OHA) Tasha Poissant, MPH (OHA) Ann Thomas, MD, MPH (OHA)

Jon Furuno, PhD (OSU College of Pharmacy) Chris Pfeiffer, MD, MHS (PVAMC, OHSU) John Townes, MD (OHSU)

DROP-CRE Network Personnel

Dianna Appelgate, MS, MPH, CIC (Sacred Heart, Springfield)

Avanthi Doppalapudi, MD (Providence, Medford) Ronald Dworkin, MD (Providence, Portland) Kendra Gohl, RN, BSN, CIC (Columbia, Astoria) Alex Kallen, MD, MPH (CDC, Atlanta GA) Margret Oethinger, MD, PhD (Providence, Portland) Robert Pelz, MD, PhD (PeaceHealth, Springfield) Kathy Phipps, RN, BSN, CPUR (Acumentra, Portland) Mary Post, RN, MS, CNS, CIC (OPSC, Portland) Pat Preston, MS (McMinnville) Sheryl Ritz, RN, BSN (Vibra, Portland) Susan Sharpe, PhD, DABMM, FAAM (Kaiser, Portland) Sarah Slaughter, MD (Providence, Portland) Cathy Stone, MT, CIC (Good Sam, Corvallis)

Advisory Committee Members

1. Assess statewide needs and capabilities for MDRO/CRE response.

2. Coordinate statewide CRE education.3. Develop capacity for rapid carbapenemase

identification.4. Offer real-time epidemiologic outbreak

assistance to Oregon facilities with CRE.5. Track CRE regionally between facilities.

DROP-CRE Network: 2012-13 Goals

Part 1: IP Needs Assessment Survey Results

IP Needs Assessment Survey:Facility characteristics

45/62 (72%) responded Response rate by bed size

◦ 5-49 beds: 21/29 (72%)◦ 50-99 beds:4/6 (66%)◦ 100-149 beds: 9/10 (90%)◦ >150 beds: 8/13 (61%)

Facility-specific definitions for MDR-Enterobacteriaciae

25%

28%6%

41%

Resistant to at least 3 classes of antimicro-bialsResistant to at least 2 classes of antimicro-bialsSusceptible to only 2 classes of antimi-crobialsOther

Are β-lactams and cephalosporins considered to

be in the “same class”?Yes 9%; Unsure 21%, No 70%

Infection Prevention Activities

Patients placed in contact precautions:◦CRE: 85%◦ ESBL: 73%◦ MDR-Pseudomonas

spp. : 69%◦ MDR-Acinetobacter

spp. : 76%◦ MRSA/VRE: 97%◦ C. diff: 100%

Activities monitored:◦ Hand hygiene: 91%◦ Isolation precautions: 79%◦ Environmental cleaning:

85% Most UV fluorescence

marker or ATP monitor◦ None: 3%

Interfacility Transfer Awareness

58% strongly agree or agree that their facility is aware of patients’ MDRO status upon admission

82% a strongly agree or agree that a receiving facility is made aware of patients’ MDRO status upon discharge

15% listed CRE amongst top 3 MDRO priorities◦ 97% MRSA and Cdiff; 61% VRE; 42% ESBL

94% aware of CDC CRE Toolkit 79% used the OHA CRE definition stated on the

survey (21% were unsure) 18/33 (55%) had not reviewed microbiology

records to detect unrecognized CRE cases◦ Of those who had reviewed, 20% (3/15) identified

CRE. No facility had conducted a CRE point

prevalence survey

CRE awareness/surveillance

Extremely valuable: ◦ Teleconference with experienced epi team during

CRE outbreak/exposure 67%◦ APIC presentation 55%◦ Site visit with experienced epi team during CRE

outbreak/exposure 55%◦ Webinar 49%◦ Educational handouts/algorithms 44%◦ Grand Rounds at your hospital 16%

Moderately or Not Valuable 68%

MDRO Educational Preferences

Definitions of MDRO-GNR vary widely IPs are often not confident whether MDRO status of

patients is communicated in transfer ~50% of facilities have reviewed microbiology

records for CRE Facilities are frequently monitoring adherence to

contact precautions (79%), hand hygiene (91%), and environmental cleaning (85%).

Thanks again to all survey participants!

Summary of the Survey

Part 2:Oregon CRE Toolkit

Photos from CDC CRE Toolkit 2012

1. Overview of the Toolkit2. Definition3. Infection Prevention/Control in Acute Care Facilities4. Infection Prevention/Control in Long Term Care Facilities5. Infection Prevention/Control in Ambulatory Care Settings6. Microbiology Laboratories: Detection and Reporting7. References8. Appendices (CRE Interfacility transfer form, CDC

environmental cleaning monitoring tool, Screening culture laboratory protocol and sample letter for staff and patients, Basic and Advanced CRE FAQ, Patient Safety Tips)

Oregon CRE Toolkit

Oregon CRE DefinitionEnterobacteriaceae that…

Are non-susceptible (i.e., intermediate or resistant) to ANY carbapenem (e.g., doripenem, ertapenem, imipenem, or meropenem)

ANDresistant to ANY of the following 3rd generation cephalosporin tested:

cefotaxime, ceftriaxone, or ceftazidime

—OR—

Possess/contain a gene sequence specific for carbapenemase (PCR)

—OR—

Are positive for carbapenemase by a phenotypic test (e.g., Modified Hodge Test)

Tier Description Organisms Included

Recommended Action

1Carbapenemase-producing CRE

•All PCR+ •MHT+ EXCEPT Enterobacter spp.

Most aggressive

control measures

2

CRE with acquired carbapenem resistance NOT due to carbapenemase production

•CRE that do not qualify as either Tier 1 or Tier 3•Includes MHT+, PCR negative Enterobacter spp.

Facility-level control

measures

3

CRE with intrinsic (natural) imipenem resistance

Proteus, Providencia and Morganella spp. with ONLY imipenem non-susceptibility

No special control

measures needed

CRE Assessment Tiers

1. Understanding Enterobacteriaceae.2. CRE: “non-susceptible” or “resistant”? 3. Low adoption rate of new CLSI breakpoints

of Enterobacteriaceae to carbapenems.4. Inability to rapidly identify the resistance

mechanism (carbapenemase vs. other).◦ And, does resistance mechanism matter for

infection control?

Challenges with defining CRE

CRE “Reference Guide”

Gram negative bacilli (rods) mostly found in the gastrointestinal tract

Laboratory basics: all ferment glucose, mostly oxidase negative

Examples: ◦Main: E. coli, Klebsiella spp., Enterobacter

spp. ◦ Other: Proteus spp., Providencia spp., Morganella

spp., Citrobacter spp., Serratia spp., Salmonella spp. Pseudomonas spp. and Acinetobacter

spp. are NOT Enterobacteriaceae.

Enterobacteriaceae

  Old Breakpoints (µg/mL)

(through Jan. 2010; M100-S19)

New Breakpoints (µg/mL) (revised Jun. 2010 and

Jan. 2012; M100-S22)

S I R S I R

Doripenem n/a n/a n/a ≤1 2 ≥4

Ertapenem ≤2 4 ≥8 ≤0.5 1 ≥2

Imipenem ≤4 8 ≥16 ≤1 2 ≥4

Meropenem ≤4 8 ≥16 ≤1 2 ≥4

CLSI Breakpoint ChangesEnterobacteriaceae to carbapenems

1. Carbapenemase (Tier 1)2. Non-Carbapenemase (Tiers 2 & 3)

Routine susceptibility testing in the microbiology laboratory does not reliably differentiate the resistance mechanism.

Categories of CRE Resistance

Carbapenemases directly inactivate carbapenems CP CRE are primarily responsible for rapid

worldwide spread of CRE. ◦ “plasmid mediated” transmission◦ Klebsiella spp. most common

Carbapenemases to know: ◦ Klebsiella pneumoniae carbapenemase (KPC)◦ New Delhi metallo-β-lactamase (NDM) ◦ Verona integron encoded metallo-β-lactamase (VIM)◦ Imipenemase metallo-β-lactamase (IMP)◦ Oxacillinase-48 (OXA-48).

Tier 1: Carbapenemase-producing (CP) CRE

Resistance mechanism is typically:◦ extended spectrum β-lactamase (ESBL) or extended

spectrum cephalosporinase (e.g. AmpC) plus

◦ decreased permeability of the cell wall (e.g. porin mutation).

Epidemiology: ◦ stable over time◦ Most often seen in Enterobacter spp.

Local (i.e. unit- or facility-wide) rather than global impact.

Tier 2: Acquired carbapenem resistance not due to carbapenemase production

Using “new” CLSI breakpoints, it is common to encounter imipenem non-susceptible organisms (MICs 2–4 µg/mL) that were considered susceptible by the “old” CLSI breakpoints.

Proteus spp., Providencia spp., and Morganella spp.◦ PVAMC Antibiogram: Morganella morganii

2009 100% imi-S2010 100% imi-S2011 20% imi-S2012 34% imi-S

Non-susceptibility to any other carbapenem is unusual and reason for concern.

Tier 3: Naturally imipenem- resistant Enterobacteriaceae

Global Epidemiology: KPC

Gupta et al. Clin Infect Dis 2011;53:60-67

Global Epidemiology: NDM

Gupta et al. Clin Infect Dis 2011;53:60-67

Global Epidemiology: VIM/IMP

Nordmann et al. Emerg Infect Dis 2011;17:1791-98

Global Epidemiology: OXA-48

Nordmann et al. Emerg Infect Dis 2011;17:1791-98

Patel, Rasheed, Kitchel. 2009. Clin Micro NewsMMWR MMWR Morb Mortal Wkly Rep. 2010 Jun 25;59(24):750.MMWR Morb Mortal Wkly Rep. 2010 Sep 24;59(37):1212.CDC, unpublished data

DC

PRAK

HI

Carbapenemase-producing CRE in the United States

KPC

KPC, NDM

KPC, NDM, VIM, IMP

KPC, NDM, VIM

KPC, NDM, OXA

Slide from Alex Kallen,MD, MPH)

CRE reported*

*

*KPC-producing CRE reported

*

Oregon CRE Epidemiology

45 CRE 3 KPC No NDM No other known

carbapenemases

Organism Number reporte

dNo.

Modified Hodge Test

PositiveNo. (%)

PCR positive for KPCNo. (%)

Enterobacter aerogenes

5 3 (60) 0

Enterobacter cloacae 25 16 (64) 0Enterobacter spp. 1 0 0Escherichia coli 2 n/a 0Klebsiella pneumoniae

9 4 (44) 3 (33%)

Proteus mirabilis 1 n/a 0Citrobacter spp 1 1 (100) 0Serratia marcescens 1 0 0Total 45 24 (53) 3 (7%)

CRE in Oregon

Different than the other carbapenems◦ No activity against Pseudomonas aeruginosa◦ Slightly weaker activity against Enterobacteriaciae

Lowest barrier to resistance via ESBL/AmpC + porin change

◦ Typical use in practice: outpatient antibiotic therapy In the lab: the most sensitive but least specific

carbapenem used to screen for CRE. ◦ For labs using the “Old” CLSI breakpoints: ertapenem

non-susceptibility may be the only indicator of CP CRE.

Ertapenem

39/48 (81%) labs responded CRE screening methods (n=37)

◦ 25 labs: automated testing only (Microscan or Vitek) 7/25 use new CLSI breakpoints

◦ 3 labs: both automated and manual testing◦ 9 labs: manual testing only

3/9 use new CLSI breakpoints Confirmatory carbapenemase testing

◦ 7/37 use Modified Hodge Test 5/7 use new CLSI breakpoints

We are encouraging labs to eitherA) Switch over to new breakpoints; or B) Perform Modified Hodge Testing. If not possible, send isolates meeting screening criteria (carbapenem MIC ≥2 and resistance to any 3rd generation cephalosporin) to OSPHL for MHT

Oregon Microbiology Laboratory Practices (from survey)

Carbapenemases not only directly hydrolyze carbapenems but also penicillins and cephalosporins

Addition of 3rd generation (IV) cephalosporins to the definition ◦ Improves specificity ◦ Does not sacrifice (much) sensitivity◦ Increases complexity

Cefepime: 4th gen cephalosporin; NOT included in the CRE definition

Why 3rd Gen Cephalosporins?

Indirect phenotypic test of carbapenemase production.

Accuracy:◦ Great: KPC detection in E. coli and

Klebsiella spp., ◦ BAD: KPC detection in Enterobacter

spp. >50% of Enterobacter spp. CRE in

Oregon are MHT+ (all are PCR neg)◦ Variable/Uncertain: non-KPC

carbapenemases

Detection of CP CRE: Modified Hodge Test (MHT)

Carbapenemase PCR (or other genotypic method) is the most accurate way to detect CP CRE.

Carbapenemase PCR testing is currently not widely available. ◦ No private labs performing the test in Oregon

We anticipate PCR to be online at OSHPL in May

Detection of CP CRE: PCR

Oregon CRE Definition (again)

Enterobacteriaceae that…

Are non-susceptible (i.e., intermediate or resistant) to ANY carbapenem (e.g., doripenem, ertapenem, imipenem, or meropenem)

ANDresistant to ANY of the following 3rd generation cephalosporin tested:

cefotaxime, ceftriaxone, or ceftazidime

—OR—

Possess/contain a gene sequence specific for carbapenemase (PCR)

—OR—

Are positive for carbapenemase by a phenotypic test (e.g., Modified Hodge Test)

1st mandated Dec, 2011 Laboratories and clinicians required to

report Report all CRE using the revised CRE case

definition Labs are asked to submit a subset of

isolates for further testing at OHA and CDC OSPHL will perform in real-time:

MHT (available now) and

PCR for KPC and NDM (available soon)

CRE Reporting in Oregon

CRE Reporting and Isolate Submission

(Appendix F)

1. Overview of the Toolkit2. Definition3. Infection Prevention/Control in Acute Care

Facilities4. Infection Prevention/Control in Long Term Care Facilities5. Infection Prevention/Control in Ambulatory Care Settings6. Microbiology Laboratories: Detection and Reporting7. References8. Appendices (CRE Interfacility transfer form, CDC

environmental cleaning monitoring tool, Screening culture laboratory protocol and sample letter for staff and patients, Basic and Advanced CRE FAQ, Patient Safety Tips)

Oregon CRE Toolkit

Educate staff (CRE and other MDR-GNRs) Communicate with your microbiology lab

◦ Use the OHA CRE definition◦ Ensure IPC is notified when CRE is detected◦ Know which CLSI breakpoints are used at your facility◦ Review past 12 months of lab records for previously

unrecognized CRE Consider active surveillance cultures for CRE

colonization in select patients on admission

General Measures for CRE Prevention in Acute Care

Notify Local Health Dept. Assess “Tier” of CRE; act accordingly

Follow the “NICE” Toolkit Recommendations

Specific Recommendations for IPC when CRE recognized at your facility

Notify: ◦ Local health department, clinician groups (ID, ICU, etc.),

antibiotic stewardship program◦ For CP-CRE: Notify hospital administration

Intervene ◦ Emphasize core strategies: hand hygiene, Contact

Precautions, private rooms, environmental cleaning◦ Reduce unnecessary antibiotics◦ Reduce use of invasive devices ◦ For CP CRE: screen patient contacts; cohort staff/patients

Communicate CRE status to any receiving facility Educate patients, staff, and visitors about CRE

Think “NICE” for CRE

1. Overview of the Toolkit2. Definition3. Infection Prevention/Control in Acute Care Facilities4. Infection Prevention/Control in Long Term Care Facilities5. Infection Prevention/Control in Ambulatory Care Settings6. Microbiology Laboratories: Detection and Reporting7. References8. Appendices (CRE Interfacility transfer form,

CDC environmental cleaning monitoring tool, Screening culture laboratory protocol and sample letter for staff and patients, Basic and Advanced CRE FAQ, Patient Safety Tips)

Oregon CRE Toolkit

2 CRE FAQs CDC Vital Signs OSTLTS PHPSF General Patient

Safety Tips

Toolkit Educational Material

Eventually we plan to add more material to OHA CRE Website including talks and slidesets

Dr. Alex Kallen’s CityWide ID presentation on CRE Feb 14, 2013 is linked below:◦ https://

www.eventbuilder.com/providence/event_desc.asp?z=506275&p_event=r4i8b8z3

What else would be helpful?

More Material

Summary The newly established DROP-CRE Network is

positioned to support Infection Preventionists efforts in MDROs/CRE prevention and control.

The IP Survey indicates room for improvement in regional CRE prevention and control.

CRE in Oregon◦ The Oregon CRE definition has been established.◦ CRE are currently rare.◦ Our particular focus is preventing spread of

carbapenemase-producing CRE around the region.◦ Use the OR CRE Toolkit as a resource for CRE prevention

control at your facilities.

Thank you!

Questions?