Alan D. Junkins, PhD, D(ABMM) of Multi-Drug-Resistant Organisms The Sponsored by an educational grant from Alan D. Junkins, PhD, D(ABMM) Louisville, KY

You know that Pseudomonas aeruginosa from Mr. Jones in 5F You know that Pseudomonas aeruginosa from Mr. Jones in 5F? Is that an MDRO?

Why do you want to know? Why are you asking me? How should I know?

Why do you want to know?

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.”

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? You do, Or whomever you’re producing the data for

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? Your infection control team

NHSN, CDC, State, Parent Company 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

for different reasons… Hence, the problem… Different people doing the defining… for different reasons… …leads to different definitions.

I know one when I see one… MRSA VRE ESBL AmpC KPC Acinetobacter …well, maybe not.

Multi – drug - resistant The Simplest Approach The Not Quite As Simple But Now The Closest Thing We Have to Universally Accepted Approach Multi – drug - resistant Resistant to > 1 drug Non-susceptible to >2 classes of drugs

Extensively drug resistant XDR and PDR Extensively drug resistant Non-susceptible to at least 1 drug in all but two or fewer classes Pan drug resistant Non-susceptible to all agents in all classes

What is a “class” of drugs? Beta-lactams

What is a “class” of drugs? Penicillins Cephalosporins Monobactams Carbapenems

What is a “class” of drugs? Aminopenicillins 1st gen. Cephalosporins Ureidopenicillins 2nd gen. Cephalosporins Carboxypenicillins 3rd gen. Cephalosporins ß-lactamase resistant penicillins 4th gen. Cephalosporins 5th gen. Cephalosporins ß-lactamase inhibitor combinations Cefamycins Monobactams Carbapenems

What is resistance to a class? Bug A Bug B Bug C Bug D Gentamicin R I Tobramycin S Amikacin Resistant 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.

I’ll refer to this later as the “GBGX” paper.

MDR – NS to at least one drug in at least 3 classes 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

MDR – NS to at least one drug in at least 3 classes 22 drugs in 17 classes 14 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

Authors recommend additional designations: “Possible XDR” “Possible PDR”

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

MRSA MSSA MDRO Definitions 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

VRE Ceph-R Klebsiella MDRO Definitions Any Enterococcus resistant to vancomycin or positive by an FDA-approved test for VRE Ceph-R Klebsiella Any Klebsiella non-susceptible to ceftriaxone, cefotaxime, ceftazidime, or cefepime*** ***Based on new breakpoints http://www.cdc.gov/nhsn/PDFs/pscManual/12pscMDRO_CDADcurrent.pdf, January 2013

CRE E. coli CRE Klebsiella MDRO Definitions CRE E. coli Non-susceptible to imipenem, meropenem, or doripenem***, or positive by a test for carbapenemase ***Based on new breakpoints CRE Klebsiella http://www.cdc.gov/nhsn/PDFs/pscManual/12pscMDRO_CDADcurrent.pdf, January 2013

MDR Acinetobacter MDRO Definitions http://www.cdc.gov/nhsn/PDFs/pscManual/12pscMDRO_CDADcurrent.pdf, January 2013

Based on new breakpoints Call this one the “CRE Toolkit” Based on new breakpoints Back to CRE http://www.cdc.gov/hai/organisms/cre/cre-toolkit/

But maybe not so straightforward… http://www.cdc.gov/hai/organisms/cre/cre-toolkit/

How many CRE at Norton*? (since January 1, 2010) 13 True Modified Hodge Positive 28 Standard definition from CDC’s “CRE Toolkit” 22 Take away imipenem-NS Proteus, Providencia, Morganella 37 Include ertapenem NS isolates *We are still using the “old” cephalosporin and carbapenem breakpoints.

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

Our MDRO Definitions

Our MDRO Definitions

Our MDRO Definitions

What about other bugs? Burkholderia cepacia Stenotrophomonas maltophilia Achromobacter xylosoxidans Streptococcus pneumoniae

Staphylococcus aureus Is this an MDRO? Staphylococcus aureus Amox/Clav R Linezolid S Ceftriaxone Oxacillin Clindamycin Rifampin Cefazolin Trim/Sulfa Daptomycin Tetracycline Erythromycin Vancomycin Gentamicin Levofloxacin No Yes GBGX: CDC:

Staphylococcus aureus Is this an MDRO? Staphylococcus aureus Amox/Clav S Linezolid Ceftriaxone Oxacillin Clindamycin R Rifampin Cefazolin Trim/Sulfa Daptomycin Tetracycline Erythromycin Vancomycin Gentamicin Levofloxacin Yes Yes? GBGX: CDC:

Enterococcus faecalis Is this an MDRO? Enterococcus faecalis Ampicillin R Linezolid Daptomycin S Penicillin Nitrofurantoin I Tetracycline Gent. Synergy Vancomycin Levofloxacin Yes No GBGX: CDC:

Enterococcus gallinarum Is this an MDRO? Enterococcus gallinarum Ampicillin S Linezolid Daptomycin Synercid Nitrofurantoin Tetracycline Gent. Synergy Vancomycin R Levofloxacin No Yes GBGX: CDC:

Acinetobacter baumannii Is this an MDRO? Acinetobacter baumannii Amikacin R Gentamicin Amp/Sulbactam I Levofloxacin Ceftazidime Meropenem Cefotaxime Tetracycline Ciprofloxacin Trim/Sulfa Cefepime Tigecycline Colistin S Tobramycin Yes Yes GBGX: CDC:

Acinetobacter baumannii Is this an MDRO? Acinetobacter baumannii Amikacin S Gentamicin Amp/Sulbactam Levofloxacin R Ceftriaxone I Meropenem Ceftazidime Tetracycline Cefotaxime Trim/Sulfa Ciprofloxacin Tobramycin Cefepime 1 3 2 4 5 2 1 Yes No GBGX: CDC:

Achromobacter xylosoxidans Is this an MDRO? Achromobacter xylosoxidans Amikacin R Imipenem S Aztreonam Levofloxacin Ceftriaxone Meropenem Ceftazidime Pip/Tazo Cefotaxime Piperacillin Ciprofloxacin Trim/Sulfa Cefepime Tetracycline Gentamicin Tobramycin Species not addressed Species not addressed GBGX: CDC:

Pseudomonas aeruginosa Is this an MDRO? Pseudomonas aeruginosa Amikacin S Imipenem Aztreonam R Levofloxacin Ceftazidime Meropenem Ciprofloxacin Pip/Tazo Cefepime Piperacillin Gentamicin I Tobramcyin 1 2 3 Yes Species not addressed GBGX: CDC:

No Is this an MDRO? Presumably Escherichia coli GBGX: CDC: Old breakpoints ESBL positive Escherichia coli Amp/Sulbactam S Ertapenem Amikacin Imipenem Ampicillin R* Levofloxacin Ceftriaxone Meropenem Ceftazidime Pip/Tazo Cefazolin Trim/Sulfa Ciprofloxacin Tetracycline Cefepime Tobramycin No Presumably GBGX: CDC:

No Is this an MDRO? Citrobacter freundii 1 2 3 Species not addressed Amp/Sulbactam R Ertapenem S Amikacin Imipenem Ampicillin Levofloxacin Ceftriaxone Meropenem Ceftazidime Pip/Tazo Cefazolin Trim/Sulfa Ciprofloxacin Tetracycline Cefepime Tobramycin 2 3 No Species not addressed GBGX: CDC:

Klebsiella pneumoniae Is this a CRE? Klebsiella pneumoniae Amp/Sulbactam R Cefazolin Ampicillin Cefepime S Amox/Clav Cefuroxime Aztreonam Ertapenem Ceftriaxone Imipenem I Ceftazidime Meropenem Cefotaxime Piperacillin Cefoxitin Pip/Tazo Yes Yes CDC: CRE Toolkit:

No Is this a CRE? Providencia rettgeri Species not addressed CDC: New breakpoints Providencia rettgeri Amp/Sulbactam R Cefazolin Ampicillin Cefepime S Amox/Clav Cefuroxime Aztreonam Ertapenem Ceftriaxone Imipenem I Ceftazidime Meropenem Cefotaxime Piperacillin Cefoxitin Pip/Tazo No Species not addressed CDC: CRE Toolkit:

No Is this a CRE? Serratia marcescens Species not addressed CDC: New breakpoints Serratia marcescens Amp/Sulbactam R Cefazolin Ampicillin Cefepime S Amox/Clav Cefuroxime Aztreonam Ertapenem Ceftriaxone Imipenem I Ceftazidime Meropenem Cefotaxime Piperacillin Cefoxitin Pip/Tazo Species not addressed No CDC: CRE Toolkit:

Is this a CRE? Perhaps Enterobacter cloacae Species not addressed CDC: Amp/Sulbactam R Cefazolin Ampicillin Cefepime S Amox/Clav Cefuroxime Aztreonam Ertapenem I Ceftriaxone Imipenem Ceftazidime Meropenem Cefotaxime Piperacillin Cefoxitin Pip/Tazo Species not addressed Perhaps CDC: CRE Toolkit:

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.

Thank your for your attention. alan.junkins@nortonhealthcare.org 502-629-7898 And thanks to Siemens for their sponsorship of this program.