The
Alan D. Junkins, PhD, D(ABMM)
of Multi-Drug-
Resistant Organisms
Sponsored by an educational grant from
Louisville, KY
Why do you want to know?
• Your own internal monitoring– “We’ve had a 35% increase in MRSA isolates this
year.”• For infection control purposes– “All patients with MDR GNB are placed in contact
precautions.”• Reporting to authorities– “We have to report all MDROs to the state.”
Why do you want to know?
• Your own internal monitoring– “We’ve had a 35% increase in MRSA isolates this
year.”• For infection control purposes– “All patients with MDR GNB are placed in contact
precautions.”• Reporting to authorities– “We have to report all MDROs to the state.
Who defines MDRO?
You do,Or whomever you’re
producing the data for
Why do you want to know?
• Your own internal monitoring– “We’ve had a 35% increase in MRSA isolates this
year.”• For infection control purposes– “All patients with MDR GNB are placed in contact
precautions.”• Reporting to authorities– “We have to report all MDROs to the state.
Who defines MDRO?
Your infection control team
Why do you want to know?
• Your own internal monitoring– “We’ve had a 35% increase in MRSA isolates this
year.”• For infection control purposes– “All patients with MDR GNB are placed in contact
precautions.”• Reporting to authorities– “We have to report all MDROs to the state.”
Who defines MDRO?
NHSN, CDC, State, Parent Company
Hence, the problem…
Different people doing the defining…
for different reasons…
…leads to different definitions.
The Simplest Approach
Multi – drug - resistant
Resistant to > 1 drug
classes of drugs>2Non-susceptible to
The Not Quite As Simple But Now The Closest Thing We Have to Universally Accepted Approach
XDR and PDR
Extensively drug resistantNon-susceptible to at least 1 drug in
all but two or fewer classes
Pan drug resistantNon-susceptible to all
agents in all classes
What is a “class” of drugs?
1st gen. CephalosporinsAminopenicillins
Monobactams Carbapenems
Ureidopenicillins
Carboxypenicillins
ß-lactamase resistant penicillins
ß-lactamase inhibitor combinations
2nd gen. Cephalosporins
3rd gen. Cephalosporins
4th gen. Cephalosporins
5th gen. Cephalosporins
Cefamycins
What is resistance to a class?
Bug A Bug B Bug C Bug DGentamicin R R R ITobramycin R R S SAmikacin R S S SResistant to this class? Yes Yes Yes Yes
What about intrinsic resistances?
• Should intrinsic resistance count toward number of classes showing resistance?
• Typically chromosomally encoded; those genetic determinants are not easily passed on to other bacteria
• But still can be bad boys – bad infections, bugs can be transmitted to others, hard to treat
If we include intrinsic resistances in our definition, then every single Acinetobacter baumannii, Burkholderia cepacia,
Pseudomonas aeruginosa, and Stenotrophomonas maltophilia we isolate would be considered MDRO.
If we include intrinsic resistances in our definition, then every single Morganella, Proteus, Providencia, and Serratia marcescens we isolate would be considered MDRO.
22 drugs in 17 classes
MDR – NS to at least one drug in at least 3 classes
XDR – NS to at least one drug in all but 2 or fewer classes
PDR – NS to all drugs in all classes
22 drugs in 17 classes14 drugs in 13 classes
MDR – NS to at least one drug in at least 3 classes
XDR – NS to at least one drug in all but 2 or fewer classes
PDR – NS to all drugs in all classes
Standardization, but is it practical?Organism What they suggest What’s on our panel
Staphylococcus aureus 22 drugs in 17 classes 14 drugs in 13 classes
Enterococcus 17 drugs in 11 classes 10 drugs in 8 classes
Enterobacteriaceae 32 drugs in 17 classes 23 drugs in 14 classes
Pseudomonas aeruginosa 17 drugs in 8 classes 11 drugs in 6 classes
Acinetobacter 22 drugs in 9 classes 14 drugs in 8 classes
MDR – NS to at least one drug in at least 3 classes
XDR – NS to at least one drug in all but 2 or fewer classes
PDR – NS to all drugs in all classes
http://www.cdc.gov/nhsn/PDFs/pscManual/12pscMDRO_CDADcurrent.pdf, January 2013
We’ll call this one the “CDC”
paper.
Based on 2008 SHEA/HICPAC Position Paper published in Inf Control & Hosp
Epidemiol, October 2008, vol. 29, no. 10
http://www.cdc.gov/nhsn/PDFs/pscManual/12pscMDRO_CDADcurrent.pdf, January 2013
MDRO Definitions
MRSA Resistant to oxacillin, methicillin, or cefoxitin, or positive by an FDA-approved test for mecA on isolated colonies or in specimens
MSSA Not a MRSA
http://www.cdc.gov/nhsn/PDFs/pscManual/12pscMDRO_CDADcurrent.pdf, January 2013
MDRO Definitions
VRE Any Enterococcus resistant to vancomycin or positive by an FDA-approved test for VRE
Any Klebsiella non-susceptible to ceftriaxone, cefotaxime, ceftazidime, or cefepime***
***Based on new breakpoints
Ceph-RKlebsiella
http://www.cdc.gov/nhsn/PDFs/pscManual/12pscMDRO_CDADcurrent.pdf, January 2013
MDRO Definitions
CRE E. coliNon-susceptible to imipenem, meropenem, or doripenem***, or positive by a test for carbapenemase
***Based on new breakpointsCRE
Klebsiella
http://www.cdc.gov/nhsn/PDFs/pscManual/12pscMDRO_CDADcurrent.pdf, January 2013
MDRO Definitions
MDR Acinetobacter
Back to CRE
http://www.cdc.gov/hai/organisms/cre/cre-toolkit/
Call this one the “CRE Toolkit”
Based on new breakpoints
How many CRE at Norton*?(since January 1, 2010)
True Modified Hodge Positive
Standard definition from CDC’s “CRE Toolkit”
Take away imipenem-NS Proteus, Providencia, Morganella
Include ertapenem NS isolates
*We are still using the “old” cephalosporin and carbapenem breakpoints.
13
28
2237
Mandatory Reporting
• Which definition to use?– Labs using old breakpoints– Labs using new breakpoints
• Infections only, or include colonization?– Mandatory surveillance?– Which method?
• CDC method• Chromogenic media
What We’ve Done• Certain organisms are designated in microbiology laboratory reports
as MDROs.
• The Microbiology Laboratory makes this determination on the basis of full susceptibility results from the MicroScan and supplemental testing if necessary.
• The chief intent is infection control. All patients infected with an isolate reported as an MDRO are put into contact precautions.
• We continue to use pre-2009 CLSI breakpoints for cephalosporins and carbapenems with supplemental testing for beta-lactamases as necessary.
• We generally do not do surveillance cultures to detect colonization, with the exception of weekly MRSA cultures in the NICU.
Our MDRO Definitions
• MRSA – by oxacillin or cefoxitin MIC or by growth on chromogenic medium
• VRE – by vancomycin MIC; E. faecalis and E. faecium only
• E. coli, Klebsiella, and Proteus mirabilis that produces ESBL enzymes
• Certain Enterobacteriaceae that produce plasmid-encoded AmpC enzymes
What about other bugs?
Burkholderia cepacia
Stenotrophomonas maltophilia
Streptococcus pneumoniae
Achromobacter xylosoxidans
Is this an MDRO?
Amox/Clav R Linezolid S
Ceftriaxone R Oxacillin R
Clindamycin S Rifampin S
Cefazolin R Trim/Sulfa S
Daptomycin S Tetracycline S
Erythromycin S Vancomycin S
Gentamicin S
Levofloxacin S
Staphylococcus aureus
GBGX: CDC:No Yes
Is this an MDRO?
Amox/Clav S Linezolid S
Ceftriaxone S Oxacillin S
Clindamycin R Rifampin S
Cefazolin S Trim/Sulfa S
Daptomycin S Tetracycline R
Erythromycin R Vancomycin S
Gentamicin S
Levofloxacin R
Staphylococcus aureus
GBGX: CDC:Yes Yes?
Is this an MDRO?
Ampicillin R Linezolid R
Daptomycin S Penicillin R
Nitrofurantoin I Tetracycline R
Gent. Synergy S Vancomycin S
Levofloxacin R
Enterococcus faecalis
GBGX: CDC:Yes No
Is this an MDRO?
Ampicillin S Linezolid S
Daptomycin S Synercid S
Nitrofurantoin S Tetracycline S
Gent. Synergy S Vancomycin R
Levofloxacin S
Enterococcus gallinarum
GBGX: CDC:No Yes
Is this an MDRO?
Amikacin R Gentamicin R
Amp/Sulbactam I Levofloxacin R
Ceftazidime R Meropenem R
Cefotaxime R Tetracycline R
Ciprofloxacin R Trim/Sulfa R
Cefepime R Tigecycline R
Colistin S Tobramycin R
Acinetobacter baumannii
GBGX: CDC:Yes Yes
Is this an MDRO?
Amikacin S Gentamicin S
Amp/Sulbactam S Levofloxacin R
Ceftriaxone I Meropenem R
Ceftazidime S Tetracycline R
Cefotaxime I Trim/Sulfa R
Ciprofloxacin R Tobramycin S
Cefepime S
Acinetobacter baumannii
GBGX: CDC:Yes No
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2
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1
2
Is this an MDRO?
Amikacin R Imipenem S
Aztreonam R Levofloxacin S
Ceftriaxone R Meropenem S
Ceftazidime R Pip/Tazo R
Cefotaxime R Piperacillin R
Ciprofloxacin S Trim/Sulfa R
Cefepime R Tetracycline S
Gentamicin R Tobramycin R
Achromobacter xylosoxidans
GBGX: CDC: Species notaddressed
Species notaddressed
Is this an MDRO?
Amikacin S Imipenem S
Aztreonam R Levofloxacin R
Ceftazidime S Meropenem S
Ciprofloxacin R Pip/Tazo S
Cefepime S Piperacillin S
Gentamicin I Tobramcyin S
Pseudomonas aeruginosa
GBGX: CDC:Yes Species notaddressed
1
2
3
Is this an MDRO?
Amp/Sulbactam S Ertapenem S
Amikacin S Imipenem S
Ampicillin R* Levofloxacin S
Ceftriaxone R* Meropenem S
Ceftazidime R* Pip/Tazo S
Cefazolin R* Trim/Sulfa S
Ciprofloxacin S Tetracycline S
Cefepime R* Tobramycin S
Escherichia coli
GBGX: CDC:Presumably No
Old breakpoints
ESBL positive
Is this an MDRO?
Amp/Sulbactam R Ertapenem S
Amikacin S Imipenem S
Ampicillin R Levofloxacin S
Ceftriaxone S Meropenem S
Ceftazidime S Pip/Tazo S
Cefazolin R Trim/Sulfa S
Ciprofloxacin S Tetracycline S
Cefepime S Tobramycin S
Citrobacter freundii
GBGX: CDC:No
1
2
3
Species notaddressed
Is this a CRE?
Amp/Sulbactam R Cefazolin R
Ampicillin R Cefepime S
Amox/Clav R Cefuroxime R
Aztreonam R Ertapenem R
Ceftriaxone R Imipenem I
Ceftazidime R Meropenem S
Cefotaxime R Piperacillin R
Cefoxitin R Pip/Tazo I
Klebsiella pneumoniae
CDC: CRE Toolkit:Yes Yes
Is this a CRE?
Amp/Sulbactam R Cefazolin R
Ampicillin R Cefepime S
Amox/Clav R Cefuroxime R
Aztreonam R Ertapenem R
Ceftriaxone R Imipenem I
Ceftazidime R Meropenem S
Cefotaxime R Piperacillin R
Cefoxitin R Pip/Tazo I
Providencia rettgeri
CDC: CRE Toolkit: NoSpecies notaddressed
New breakpoints
Is this a CRE?
Amp/Sulbactam R Cefazolin R
Ampicillin R Cefepime S
Amox/Clav R Cefuroxime R
Aztreonam S Ertapenem S
Ceftriaxone S Imipenem I
Ceftazidime S Meropenem S
Cefotaxime S Piperacillin R
Cefoxitin R Pip/Tazo S
Serratia marcescens
CDC: CRE Toolkit: NoSpecies notaddressed
New breakpoints
Is this a CRE?
Amp/Sulbactam R Cefazolin R
Ampicillin R Cefepime S
Amox/Clav R Cefuroxime R
Aztreonam R Ertapenem I
Ceftriaxone R Imipenem S
Ceftazidime R Meropenem S
Cefotaxime R Piperacillin R
Cefoxitin R Pip/Tazo I
Enterobacter cloacae
CDC: CRE Toolkit: PerhapsSpecies notaddressed
So what to do?
• Will the lab designate isolates as MDRO?• Why? What’s your purpose? How will the data be
shared?• Create meaningful definitions that fit your purpose.• Continue to follow good selective reporting, but
include non-reported drugs in determining MDRO status.
• Make determination of MDRO status as easy as possible. Automate if possible.
And thanks to Siemens for their sponsorship of this program.
Thank your for your attention.