Christopher D. Pfeiffer, MD, MHS
OSWAPIC Chapter Meeting
April 9, 2013
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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.
CRE
Initiated September
2012
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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)
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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)
1.
2.
3.
4.
5.
Assess statewide needs and capabilities for
MDRO/CRE response.
Coordinate statewide CRE education.
Develop capacity for rapid carbapenemase
identification.
Offer real-time epidemiologic outbreak
assistance to Oregon facilities with CRE.
Track CRE regionally between facilities.
IP Needs Assessment Survey Results
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45/62 (72%) responded
Response rate by bed size
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5-49 beds: 21/29 (72%)
50-99 beds:4/6 (66%)
100-149 beds: 9/10 (90%)
>150 beds: 8/13 (61%)
Resistant to at least 3
classes of
25%
antimicrobials
41%
Resistant to at least 2
classes of
28%
6%
antimicrobials
Susceptible to only 2
classes of
antimicrobials
Other
Are β-lactams and cephalosporins
considered to be in the “same class”?
Yes 9%; Unsure 21%, No 70%
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Patients placed in
contact precautions:
◦ CRE: 85%
◦ ESBL: 73%
◦ MDR-Pseudomonas
spp. : 69%
◦ MDR-Acinetobacter
spp. : 76%
◦ MRSA/VRE: 97%
◦ C. diff: 100%
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Activities monitored:
◦ Hand hygiene: 91%
◦ Isolation precautions: 79%
◦ Environmental cleaning: 85%
 Most UV fluorescence marker
or ATP monitor
◦ None: 3%
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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
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15% listed CRE amongst top 3 MDRO priorities
◦ 97% MRSA and Cdiff; 61% VRE; 42% ESBL
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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.
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No facility had conducted a CRE point prevalence
survey
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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%
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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!
Oregon CRE Toolkit
Photos from CDC CRE Toolkit 2012
1.
Overview of the Toolkit
2.
Definition
3.
4.
5.
6.
7.
8.
Infection Prevention/Control in Acute Care Facilities
Infection Prevention/Control in Long Term Care Facilities
Infection Prevention/Control in Ambulatory Care Settings
Microbiology Laboratories: Detection and Reporting
References
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)
Enterobacteriaceae that…
Are non-susceptible (i.e., intermediate or resistant) to
ANY carbapenem (e.g., doripenem, ertapenem, imipenem, or meropenem)
AND
resistant 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)
Organisms Included
Recommended
Action
1
Carbapenemaseproducing 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
CRE with intrinsic
(natural)
imipenem
Proteus, Providencia and
Morganella spp. with ONLY
No special
control
measures
Tier
3
Description
imipenem non-susceptibility
Understanding Enterobacteriaceae.
CRE: “non-susceptible” or “resistant”?
Low adoption rate of new CLSI breakpoints of
Enterobacteriaceae to carbapenems.
Inability to rapidly identify the resistance
mechanism (carbapenemase vs. other).
1.
2.
3.
4.
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And, does resistance mechanism matter for
infection control?
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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.
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Pseudomonas spp. and Acinetobacter spp.
are NOT 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
1.
2.
Carbapenemase (Tier 1)
Non-Carbapenemase (Tiers 2 & 3)
Routine susceptibility testing in the
microbiology laboratory does not reliably
differentiate the resistance mechanism.
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Carbapenemases directly inactivate carbapenems
CP CRE are primarily responsible for rapid
worldwide spread of CRE.
◦ “plasmid mediated” transmission
◦ Klebsiella spp. most common
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Carbapenemases to know:
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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).
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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).
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Epidemiology:
◦ stable over time
◦ Most often seen in Enterobacter spp.
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Local (i.e. unit- or facility-wide)
rather than global impact.
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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
2010
2011
2012
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100% imi-S
100% imi-S
20% imi-S
34% imi-S
Non-susceptibility to any other carbapenem is unusual
and reason for concern.
Gupta et al. Clin Infect Dis 2011;53:60-67
Gupta et al. Clin Infect Dis 2011;53:60-67
Nordmann et al. Emerg Infect Dis 2011;17:1791-98
Nordmann et al. Emerg Infect Dis 2011;17:1791-98
Slide from Alex Kallen,MD, MPH)
DC
KPC
KPC, NDM
HI
PR
AK
Patel, Rasheed, Kitchel. 2009. Clin Micro News
MMWR 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
KPC, NDM,
OXA
KPC, NDM,
VIM
KPC, NDM,
VIM, IMP
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45 CRE
3 KPC
No NDM
No other known
carbapenemases
*
*
CRE reported
*KPC-producing CRE
reported
*
Number
reported
Modified Hodge
Test Positive
PCR positive for
KPC
Enterobacter aerogenes
No.
5
No. (%)
3 (60)
No. (%)
0
Enterobacter cloacae
Enterobacter spp.
Escherichia coli
Klebsiella pneumoniae
25
1
2
9
16 (64)
0
n/a
4 (44)
0
0
0
3 (33%)
Proteus mirabilis
Citrobacter spp
Serratia marcescens
1
1
1
45
n/a
1 (100)
0
24 (53)
0
0
0
3 (7%)
Organism
Total
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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
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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.
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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
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Confirmatory carbapenemase testing
◦ 7/37 use Modified Hodge Test
 5/7 use new CLSI breakpoints
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We are encouraging labs to either
A) 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
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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
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Cefepime: 4th gen cephalosporin; NOT
included in the CRE definition
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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
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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
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We anticipate PCR to be online at OSHPL in May
Enterobacteriaceae that…
Are non-susceptible (i.e., intermediate or resistant) to
ANY carbapenem (e.g., doripenem, ertapenem, imipenem, or meropenem)
AND
resistant 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)
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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)
2.
Overview of the Toolkit
Definition
3.
Infection Prevention/Control in Acute Care Facilities
1.
4.
5.
6.
7.
8.
Infection Prevention/Control in Long Term Care Facilities
Infection Prevention/Control in Ambulatory Care Settings
Microbiology Laboratories: Detection and Reporting
References
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)
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Educate staff (CRE and other MDR-GNRs)
Communicate with your microbiology lab
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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
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Notify Local Health Dept.
Assess “Tier” of CRE; act accordingly
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Follow the “NICE” Toolkit Recommendations
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Notify:
◦ Local health department, clinician groups (ID, ICU, etc.),
antibiotic stewardship program
◦ For CP-CRE: Notify hospital administration
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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
2.
Overview of the Toolkit
Definition
3.
Infection Prevention/Control in Acute Care Facilities
1.
4.
5.
6.
7.
8.
Infection Prevention/Control in Long Term Care Facilities
Infection Prevention/Control in Ambulatory Care Settings
Microbiology Laboratories: Detection and Reporting
References
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)
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2 CRE FAQs
CDC Vital Signs
OSTLTS PHPSF
General Patient
Safety Tips
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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_d
esc.asp?z=506275&p_event=r4i8b8z3
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What else would be helpful?
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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.