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Antibiotic Resistance Surveillanceand Public Health
Maureen Cassidy, Epidemiologist,ACDP/HAI Program
12/13/2017
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https://www.cdc.gov/drugresistance/biggest_threats.html
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Objectives
• How antibiotics work• Mechanisms of resistance in gram negative bacteria• Laboratory testing to determine resistance• Carbapenem-Resistant Enterobactericeae (CRE)• CRE special considerations• New surveillance for other multi-drug resistant
organisms (MDRO)
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How antibiotics work• Interfere with bacterial cell wall synthesis
– β-lactam antibiotics; penicillin, cephalosporins
• Inhibit protein synthesis– aminoglycosides, tetracyclines
• Interfere with nucleic acid synthesis– fluoroquinolines
• Inhibit a metabolic pathway– Sulfonamides, trimethoprim
• Disorganize the cell membrane– Polymyxin, daptomycin
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Antibiotic classes and enzymes mediating resistanceDrug Class Antibiotic Examples Resistance Mechanism
β-lactams Penicillin, Amoxicillin β-lactamases
β-lactam/β-lactamase inhbitors
Amoxicillin-clavulanic acid (Augmentin)
Extended-spectrum β-lactamases (ESBL)
Cephalosporins Cephalexin (Keflex)Ceftriaxone (Rocephin)Cefepime (Maxipime)
Extended spectrum cephalosporinases (e.g.,AMP C)
Carbapenems ErtapenemImipenemMeropenemDoripenem
Carbapenemases
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https://www.cdc.gov/antibiotic‐use/community/about/antibiotic‐resistance‐faqs.html
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Antibiotic resistance continued
• Antibiotic degrading enzymes can be chromosomal or plasmid mediated
• Plasmid mediated enzymes can move easily from one bacteria to another, one species to another
• Plasmids – mobile particles of DNA
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Plasmid transfer of resistance #1
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Photo credit: http://www.usatoday.com/story/news/nation/2012/11/29/bacteria-deadly-hospital-infection/1727667/
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Plasmid transfer of resistance #2
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Photo credit: http://www.usatoday.com/story/news/nation/2012/11/29/bacteria-deadly-hospital-infection/1727667/
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Plasmid transfer of resistance #3
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Photo credit: http://www.usatoday.com/story/news/nation/2012/11/29/bacteria-deadly-hospital-infection/1727667/
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Laboratory testing to determine susceptibility/resistance
• Minimum inhibitory concentration (MIC):Lowest concentration of an antimicrobial drug that inhibits the growth of a microorganism after overnight incubation
• Breakpoint:Level of the antibiotic concentration that determines susceptibility or resistance
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Laboratory results
• Automated systems; primarily Vitek
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Vitek Microscan
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Other laboratory testing for resistance
• Kirby Bauer disk diffusion– Disk with concentration of antibiotic– Correlates with MIC– Zone sizes
• E-Test– Gradient of antibiotic on a strip– Provides MIC
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Why we care
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Carbapenem-resistant Enterobacteriaceae (CRE)
• Enterobacteriaceae – Gram negative bacilli of the gastrointestinal tract– E. coli, Klebsiella, Enterobacter
• Carbapenems – class of β-lactam antibiotics with a broad spectrum of antibacterial activity – Considered antibiotics of last resort
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CRE definition and breakpoints for resistance
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Current MIC Breakpoints (µg/mL)1MIC Interpretation2
Carbapenems Susceptible Intermediate ResistantDoripenem ≤1 2 ≥4Ertapenem ≤0.5 1 ≥2Imipenem ≤1 2 ≥4Meropenem ≤1 2 ≥4
1MIC = minimum inhibitory concentration2CLSI. Performance Standards for Antimicrobial Susceptibility Testing Twenty-Fifth Informational SupplementCLSI document M100-S25, Wayne, PA: Clinical and Laboratory Standards Institute: January 2015.
Current Disk Diffusion Zone Diameters (mm)3Zone Size Interpretation2
Carbapenems Susceptible Intermediate ResistantDoripenem ≥23 20–22 ≤19Ertapenem ≥22 20–21 ≤18Imipenem ≥23 20–21 ≤18Meropenem ≥23 20–21 ≤18
3mm = millimeters2CLSI. Performance Standards for Antimicrobial Susceptibility Testing Twenty-Fifth Informational SupplementCLSI document M100-S25, Wayne, PA: Clinical and Laboratory Standards Institute: January 2015.
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Clinical laboratory testing• Labs may suppress carbapenem values on their
lab information system reports– Example: a lab may test both ertapenem and
imipenem but only imipenem will be reported via ELR
– LHD may get the report as CRE, not have the ertapenem MICs, imipenem MIC will indicate sensitive
• Automated systems can be set to convert carbapenem interpretations to resistant based on MICs of cephalosporins
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Example of MICs in ELR
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CRE terminology
• Carbapenemase producing (CP-CRE)– Responsible for rapid global plasmid mediated
spread!!– Directly inactivate carbapenems– Increased morbidity and mortality
• Non-carbapnemase-producing (CRE) – Stable/slight increase incidence over time– Multiple mechanisms combined for resistance –
AmpC, porin changes23
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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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OSPHL Carbapenemase testing
• Labs submit isolates to OSPHL with the automated system print outs
• Print outs are faxed to ACDP• Carbapenemase testing is done weekly
– Carba NP– Multiplex PCR
• OXA-48 only, if Carba NP is negative• All 5 carbapenemases if Carba NP positive
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Spread of CP CRE in the US
• KPC first discovered in 2000• Now
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CRE prevalence varies– Region: Israel Chicago Oregon
Unidentified CRE in inter-facility patient transfer promotes outbreaks
CRE prevalence
Won S. et al. Clin Infect Dis 2011;53:532-40
n=10n=14n=2n=40
KPC outbreak, Chicago-area, 2008Figure: Exposure Network Analysis
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Healthcare out of Oregon and CP-CRE
• Oregon is still a low prevalence state• 17/496 (3%) of Oregon cases are CP-CRE• 12/17 (75%) CP-CRE cases had history of
healthcare out of state
• Compare to Minnesota - 21% of CRE isolates were KPC, CP-CRE in 2015
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Focus of CRE or any MDRO investigation• Prevent spread
– Identify and confirm– Inform facility
• Verify precautions (contact)
– Provide education• Carrier of resistant organism• hand hygiene importance• precautions if hospitalized
– Transfer notification – flagging chart
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How does CP-CRE Investigation Differ
• LHD and OHA will work together on screening cultures for high risk contacts– Send to OSPHL– Recommended site: rectal swabs
• Cohorting of staff is recommended • LHD should be notified when case
transfers
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Other MDRO
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Other resistant organisms
• Mobilized Colistin Resistance genes (MCRs 1, 2, 3 and ………..)
• Plasmid mediated – resistance to last line drug - colistin
• Found in China 2 years ago• Now in >30 countries
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Nov 20151st report:
China
Mar 2016Food animals &
humans in 12 countries each;
Food in 8 countries
Apr 2016 1st report
USA
Aug 2016 1st report USA w/
CRE
Sept 2016Another US Report
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Additional surveillance for Multi-Drug-Resistant Organisms (MDROs)
• Multi-site Gram-Negative Surveillance Initiative (MuGSI), Portland tri-county – Carbapenem-resistant Pseudomonas aeruginosa
(CRPA)– Carbapenem-resistant Acinetobacter baumannii
(CRAB)
• Candidemia surveillance – Emerging Infections Program
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New Surveillance for MDROs
• OSPHL request to clinical labs• Submit isolates of pan-resistant gram
negatives– test for carbapenemases
• Submit possible Candida auris isolates– newly recognized species– resistant to antimicrobials– cause of outbreaks in other states
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New surveillance for MDROs
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New surveillance for MDROs
• Expanding surveillance for – Carbapenem-resistant Pseudomonas aeruginosa
(CRPA)– Carbapenem-resistant Acinetobacter baumannii
(CRAB)
• Select laboratories statewide will send isolates
• Surveillance for MCRs– Test E.coli and Klebsiella spp. resistant to all 3rd
generation cephalosporins
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Thanks for contributions to this presentation
• Chris Pfeiffer, MD, MHS• Ann Thomas, MD• Rebecca Pierce, PhD, MS, BSN
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New CDC project
Combating Antibiotic Resistant Bacteria (CARB)
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Julie Hatch, MT, ASCPLaboratory Surveillance Coordinator
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Whole Genome Sequencing (WGS)
• Detect different types of antibiotic resistance
• Detect plasmids• Certain types of resistance are associated
with different parts of the world
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2018 Interview Changes
• Salmonella• Campylobacter
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New Interview Questions
• Severity of illness – Duration of illness, admission to ICU
• Health conditions – Diabetes, cancer, bowel surgery
• Probiotic and antacid use • Antibiotic use• Travel
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National Antibiotic Resistance Monitoring System (NARMS)
• Tests every 20th Salmonella isolate from all states for antibiotic resistance
• Campylobacter submitted by FoodNet states
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Notified by CDC NARMS team
• 2014 case with MCR-3 resistance• First identified case in US
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Salmonella I 4,5,12:i:-
• 29 y F, white, non-Hispanic• Onset 7/22/14 non-bloody diarrhea• Stool collected 7/29/14• No foreign travel during exposure period• Returned from Cambodia 18 days prior to
onset
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