Infectious Disease Epidemiology Epidemiology Resource Center Indiana State Department of Health CPCRE and the nonKPCs Overview Definitions Review of antibiotic resistance CRE and CPCRE CPCRE data ID: 752788
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DJ Shannon, MPH Antimicrobial Resistance EpidemiologistInfectious Disease EpidemiologyEpidemiology Resource CenterIndiana State Department of Health
CP-CRE and the non-KPCsSlide2
OverviewDefinitionsReview of antibiotic resistanceCRE and CP-CRECP-CRE dataA closer look at the non-KPCsColonization screening overviewSlide3
DefinitionsMultidrug-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 treatmentPandrug-resistant organism (PDRO): microorganisms that are resistant to all antimicrobial agents that would be considered for treatmentSlide4
Mechanisms of Antibiotic ResistanceAntibiotic target changesPorin mutationsEfflux pumpsEnzymatic inhibitionSlide5
Mechanisms of Antibiotic ResistanceSlide6
Antibiotic Target ChangesBacteria can change a site that an antibiotic would normally targetThis can quickly lead to resistance bacterial populationsExample:Penicillin-binding protein modificationSlide7
Porin Mutations
Porins are found in the outer membrane of Gram-negative bacteriaPorins help transport material in and out of the cell
Mutations, often a reduction in
porin
production, can cause resistance to antibioticsSlide8
Efflux PumpsA very efficient mechanism of antibiotic resistanceEfflux pumps actively remove antibiotics from within the cell wallCertain types of efflux pumps can cause multidrug-resistanceExample: Efflux pumps found in Pseudomonas aerugionsaSlide9
Enzymatic InhibitionThe most common mechanism of antibiotic resistanceEnzymes produced by bacteria can inactivate the antibioticß-lactamasesPenicillinasesAmpC cephalosporinasesExtended-spectrum ß-lactamases (ESBL)Carbapenemases Slide10
Mobility of CarbapenemasesSlide11
CarbapenemasesKPC: Klebsiella pneumoniae carbapenemaseMost common in the United StatesNDM: New Delhi Metallo-ß-lactamaseMost common in IndiaIMP: ImipenemaseMost common in JapanVIM: Verona Integron-mediated Metallo-ß- lactamase
Most common in western EuropeOXA-48: Oxacillinase-48 Most common in Mediterranean countriesSlide12
CRE: A Public Health ThreatCRE in the United States are an urgent threatCRE infections are associated with high mortality ratesCRE confer high levels of resistanceCP-CRE have very mobile resistance genes that can easily be shared with other organisms (CPOs)Slide13
Carbapenem-Resistant EnterobacteriaceaeDefinition: Any Enterobacteriaceae that are not susceptible (i.e. intermediate or resistant) to a carbapenem antibioticCurrent Breakpoint (CLSI M100-S27) MIC µg/mlAntibiotic
SusceptibleIntermediateResistant
Doripenem
≤ 1
2
≥ 4
Ertapenem
≤ 0.5
1
≥ 2
Imipenem
≤ 1
2
≥ 4
Meropenem
≤ 1
2
≥ 4Slide14
Carbapenem-Resistant EnterobacteriaceaeEnterobacteriaceae can be resistant to carbapenems through several resistance mechanismsCarbapenemase production is currently the most concerningSlide15
Carbapenemase-Producing Carbapenem-Resistant EnterobacteriaceaeEnterobacteriaceae isolates that demonstrate carbapenemase production via one of the following:Positive for carbapenemase production by a phenotypic test (e.g., Carba NP, mCIM)Positive for a carbapenemase gene markerSlide16
CRE vs. CP-CRECP-CRE !!!
Reportable
+ ESBLSlide17
Indiana CP-CRE Cases, 2016-2018MonthCasesAverage:
28
Total: 355
2017
2016
Total: 294
2018
Total:
230
*Preliminary 2018 data represents 1/1/2018 –
7/31/2018Slide18
Indiana CP-CRE Cases by District, 2016-2018
State:
879
District 1:
380
District 2:
30
District 3:
70
District 4:
19
District 5:
200
District 6:
90
District 7:
51
District 8:
17
District 9:
17
District 10:
5
*Preliminary 2018 data represents 1/1/2018 –
7/31/2018Slide19
Organisms664 Klebsiella pneumoniae70 Serratia marcescens53 Escherichia coli42 Enterobacter cloacae
complex19
Citrobacter
freundii
complex
15
Klebsiella
oxytoca
6
Citrobacter koseri
4
Proteus mirabilis
2
Klebsiella aerogenes
2
Providencia
rettgeri
1
Klebsiella ozaenae
1
Klebsiella
variicola
1
Leclercia adecarboxylata
1
Morganella
morganii
Mechanisms
804
KPC
22 NDM
18 VIM
9 OXA-48-like
2 IMP
24
unknown
Indiana CP-CRE
Cases, 2016-2018
879 CP-CRE cases
*Preliminary 2018 data represents 1/1/2018 –
7/31/2018Slide20
A Closer Look at the non-KPCsNDM: New Delhi Metallo-ß-lactamaseIMP: ImipenemaseVIM: Verona Integron-mediated Metallo-ß-lactamase
Most clinically threatening
More
resistant
More mobile
Fewer antibioticsSlide21
*Preliminary 2018 data represents 1/1/2018 – 7/31/2018Indiana NDM cases
by healthcare facility,
2016-2018Slide22
*Preliminary 2018 data represents 1/1/2018 – 7/31/2018
Indiana VIM
c
ases
by
healthcare facility
,
2016-2018Slide23
*Preliminary 2018 data represents 1/1/2018 – 7/31/2018
Indiana IMP
cases
by
healthcare facility
,
2016-2018Slide24
A Closer Look at the non-KPCsOXA-48: Oxacillinase-48
Less resistant*
Difficult to detect
*Unless other mechanism presentSlide25
*Preliminary 2018 data represents 1/1/2018 – 7/31/2018
Indiana OXA
cases
by healthcare facility
,
2016-2018Slide26
AST Profile Cheat SheetDrugESBLAmpC1st –gen cephR
R2nd –gen ceph
S
R
3
rd
–gen
ceph
R
R
4
th
–gen
ceph
R
S
Pip-
tazo
S
R
Carbapenems
S
Erta
R, others S
CP-CRE bonus: If Aztreonam is resistant,
t
hink KPC – not NDM/VIM/IMPSlide27
Infection Prevention ImplicationsHealthcare Personnel EducationIdentificationLaboratory notificationInter-facility communicationScreening contacts of CRE patientsActive surveillance for CRE colonizationPreventionCareful use of invasive medical devicesAntibiotic Stewardship
ContainmentHand hygieneContact precautions
Cohorting
of residents and staff
Environmental cleaning
Chlorhexidine bathingSlide28
Antibiotic Resistance Laboratory NetworkSlide29
Tier 1: Novel resistance, rare resistant organisms or pandrug-resistant organismsExample: Candida aurisTier 2: Known, yet uncommon, resistance mechanismsExample: VIM-producing EnterobacteriaceaeTier 3: Targeted, non-endemic resistance mechanismExample: KPC-producing Enterobacteriaceae
Response TiersSlide30
Photo Source: CDC
Response TiersSlide31
What happens after colonization screening?Contact precautions useIndefinite use for CP-CRESee SHEA Guidelines RetestingWhen a negative isn’t really a negative…Patient and staff cohorting as neededSharing isn’t caring
To treat or not to treat?Slide32
ResourcesFacility Guidance for Control of CRESlide33
ResourcesManagement of Multidrug-Resistant Organisms In Healthcare Settings, 2006 Slide34
ResourcesSHEA Expert Guidance for the Duration of Contact Precautions for Acute-Care Settings Slide35
Contact InformationDJ Shannon, MPHAntimicrobial Resistance EpidemiologistInfectious Disease EpidemiologyEpidemiology Resource CenterIndiana State Department of Health
Work: 317-233-1306Email: dshannon1@isdh.in.gov