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Transcript
Carbapenemase-Producing
Carbapenem-Resistant
Enterobacteriaceae
DJ Shannon
Multidrug-Resistant Organism Epidemiologist
Infectious Disease Epidemiology
Epidemiology Resource Center
Indiana State Department of Health
Overview
• Definitions
• Antibiotic resistance
– Spread
– Mechanisms of action
• CRE and CP-CRE
– MDRO Reporting
• Laboratory aspects
• Infection control and prevention
• IP Video Conference Series
Definitions
• Multidrug-resistant organism (MDRO): an
organism that is resistant to one or more agent in at
least three classes of antibiotics – or that exhibits a
classification of resistance that is of epidemiological
concern (e.g. MRSA, VRE, ESBL, CRE)
• Extensively drug-resistant organism (XDRO):
microorganisms that are resistant to nearly all
antimicrobial agents that would be
considered for treatment
Definitions
• Pan-resistant organism: microorganisms
that are resistant to all antimicrobial agents
that would be considered for treatment
Mechanisms of Antibiotic Resistance
•
•
•
•
•
Penicillin-binding protein modifications
Porin mutations
Efflux pumps
Antibiotic target changes
Enzymatic inhibition
Enzymatic Inhibition
• ß-lactamases
– AmpC cephalosporinases
• Confers resistance to cephalosporins (and many penicillins)
– Extended-spectrum ß-lactamases (ESBL)
• Confers resistance to penicillins and cephalosporins
• Can also exhibit coresistance to tetracyclines, sulfonamides, and
aminoglycoside
• Some ESBLs confer resistance to fluoroquinolones
– Carbapenemases
• Capable of inactivating all ß-lactam antibiotics
(except Aztreonam)
Carbapenemases
• Class A Carbapenemases
– Klebsiella pneumoniae carbapenemase (KPC)
• Confers resistance to all ß-lactams
• Susceptible to ß-lactamase inhibitors
Carbapenemases
• Class B Carbapenemases
– Metallo-ß-lactamases (MBLs)
– MBLs break down all ß-lactams, except
aztreonam
– High mobility poses an infection control threat
– Examples:
• New Delhi Metallo-ß-lactamase (NDM)
• Imipenemase (IMP)
• Verona Integron-mediated Metallo-ßlactamase (VIM)
Carbapenemases
• Class D Carbapenemases
– Confers low-level resistance to carbapenems
unless in the presence of other ß-lactamases
– Not very efficient at breaking down 3rd generation
cephalosporins
– Example:
• Oxacillinase-48 (OXA-48)
Mobility of Carbapenemases
– Carbapenemase genes are found on plasmids
– Horizontal gene transfer
• This occurs when a gene conferring resistance moves
from one bacterial cell to another
• Methods:
• Conjugation
• Transduction
• Transformation
CRE: A Public Health Threat
• CP-CRE in the United States are an urgent threat
• CP-CRE infections are associated with high mortality
rates
• CP-CRE confer high levels of resistance
• CP-CRE have very mobile resistance genes that can
easily be shared with other organisms (CP-CROs)
Carbapenem-Resistant
Enterobacteriaceae
• Definition: Any Enterobacteriaceae that are
not susceptible (i.e. intermediate or resistant)
to a carbapenem antibiotic
• Enterobacteriaceae can be resistant to
carbapenems through several resistance
mechanisms
• Carbapenemase production is
currently the most concerning
Carbapenemase-Producing
Carbapenem-Resistant
Enterobacteriaceae
• Enterobacteriaceae that are not susceptible
(i.e. intermediate or resistant) to at least one
carbapenem antibiotics
– AND one of the following:
• Positive for carbapenemase production by a phenotypic
test
• Not susceptible to at least three carbapenem antibiotics
– OR:
• Positive for a carbapenemase gene marker
CRE vs. CP-CRE
CarbapenemResistant
Enterobacteriaceae
NonCarbapenemases
PBP
mutation
Efflux
Pumps
CP-CRE !!!
Carbapenemases
Porin
Mutations
KPC
NDM, VIM,
IMP
Reportable
OXA
Risk Factors of CRE
• Recent healthcare exposure
– ACH, LTC, LTACH
• Recent medical procedures
• Recent invasive device use
– Mechanical ventilator, PICC line, Foley catheter
• Recent antibiotic use
• Prior history of MDRO colonization or
infection
Laboratory Aspects
• Culture
• Antibiotic Susceptibility
– Minimum Inhibitory Concentration (MIC)
• Phenotypic Tests
– Modified Hodge test, CarbaNP, Carbapenemase
Inhibition method (CIM), modified CIM (mCIM)
• Molecular Tests
– PCR
Infection Prevention
Implications for CRE
Facility-Level Prevention Strategies
• Hand Hygiene
• Contact Precautions
• Healthcare Personnel
Education
• Use of Devices
• Laboratory Notification
• Inter-facility
Communication
• Antibiotic Stewardship
• Environmental Cleaning
• Patient and Staff
Cohorting
• Screening Contacts of
CRE Patients
• Active Surveillance
Testing
• Chlorhexidine Bathing
Indiana CP-CRE 2016 Data
354 CP-CRE cases
•
•
•
•
•
•
•
•
281 Klebsiella pneumoniae
22 Serratia marcescens
21 Escherichia coli
20 Enterobacter cloacae
complex
5 Citrobacter freundii
3 Proteus mirabilis
1 Citrobacter amalonaticus
1 Enterobacter aerogenes
•
•
•
•
•
•
334 KPC
4 NDM
4 VIM
2 OXA-48
1 SME
9 unknown
2016 CP-CRE
Counts by District
State: 354
District 1: 153
District 2: 13
District 3: 38
District 4: 8
District 5: 79
District 6: 42
District 7: 5
District 8: 11
District 9: 5
District 10: 0
I-NEDSS CDR Submission
• Please attach the following:
– History and physical
– Associated antibiotic susceptibility labs
– Medication history
• Additional information:
– Start date of contact precautions
– Healthcare exposure history
– Travel history
Resources
• Facility Guidance for Control of CRE
– Google: CDC CRE Toolkit
Resources
• Guidance for a Health Response to Contain
Novel or Targeted MDROs
– Google: CDC contain novel MDRO
New Video Conference Series
• The ISDH Epidemiology Resource Center is
launching a video conference series for
infection preventionists in Indiana
• Video conference will focus on HAIs, MDROs,
antibiotic stewardship, and feature hot topics
from other subject matter experts
New Video Conference Series
• The first IN-HASARD video conference will be
held via WebEx on Friday, April 28th from
1-2 PM EST.
• Need an invite? Email Janae Meyers, ISDH
Antibiotic Stewardship Epidemiologist, at
[email protected]
Contact Information
DJ Shannon
Multidrug-Resistant Organism Epidemiologist
Infection Disease Epidemiology
Epidemiology Resource Center
Indiana State Department of Health
Work: 317-233-1306
Email: [email protected]