Carbapenem-resistant Enterobacteriaceae (CRE) in Connecticut: Collaborative Development of a Characterization Panel and Testing of Carbapenemase Genetic Markers, 2017 Noelisa Montero, MPH Epidemiologist Consultant October 19, 2017 Connecticut Department of Public Health Healthcare Associated Infections Program Disclaimer: The content of this presentation is solely the responsibility of the author and do not represent the official views of the Centers for Disease Control and Prevention.
Bacterial Main Methods of Resistance Bacterial Genome Mutation Alter the drug target usually at the binding site Efflux Pump The antibiotic to enter the cell normally Then actively pump the drug out against the concentration gradient before the drug can affect its target http://priyava.blogspot.com/2009/10/mi crobial-biotechnology-antibiotics.html
Bacterial Main Methods of Resistance Antibiotic altering enzymes Alter the chemical makeup or structure of the drug preventing it from affecting its target Antibiotic degrading enzyme Break down the drug preventing it from harming the bacterial cell http://priyava.blogspot.com/2009/10/mi crobial-biotechnology-antibiotics.html
CRE Methods of Resistance Resistance to carbapenems can be the result of multiple resistance mechanisms: Carbapenemase enzymes Efflux pumps Porin loss Amp C hyperexpression 4
CRE Methods of Resistance Resistance to carbapenems can be the result of multiple resistance mechanisms: Carbapenemase enzymes Efflux pumps Porin loss Amp C hyperexpression Actively degrade the carbapenem antibiotics resulting in a loss of activity The subset of CRE that carry these carbapenemase genes are referred to as carbapenemase-producing CRE or CP-CRE Much of the current rise in CRE in the United States is likely due to the spread of carbapenamase-producing strains KPC NDM OXA-48 VIM IMP 5
CRE Methods of Resistance Resistance to carbapenems can be the result of multiple resistance mechanisms: Carbapenemase enzymes Efflux pumps Porin loss Amp C hyperexpression How resistance spreads Chromosomal DNA Plasmid DNA Resistant gene 6
CRE Surveillance CRE laboratory reportable in CT since January 2014 Definition updated in 2016 to align with CDC case definition All genus/species of Enterobacteriaceae All sterile sites, sputum, urine (NOT reportable from stool) Report incident case once every 30 days HAI Program staff follows-up on all reported cases Data from chart review is entered/stored into an Access database Current transition of CRE database to CTEDSS (Maven) Platform 7
CRE Surveillance Phenotypic definition based on the susceptibility pattern for antimicrobial drugs tested at the clinical labs Intended to capture all isolates that carry plasmid-based carbapenemase genes Limited availability of genetic marker testing in clinical labs NEED SPECIFIC IDENTIFICATION OF CP-CRE 8
Antibiotic Resistance Laboratory Network (ARLN) In 2016, CDC established the ARLN Provide resources to state public health laboratories & 7 regional laboratories Intended to expand the availability of advanced CRE characterization testing Enhance a coordinated response effort to track changes in resistance Help identify and respond to outbreaks faster
Antibiotic Resistance Laboratory Network http://www.cdc.gov/drugresistance/solutions-initiative/ar-lab-networks.html#how 1 0
1 1 Collaborative Development of a Characterization Panel FY2016 CT funding for Antimicrobial Resistance/Antimicrobial Stewardship (AR/AMS) Multidisciplinary Advisory Group: CRE surveillance Specimen collection Lab characterization at State Public Health Laboratory (SPHL) September 2016 1 st AR/AMS Advisory Group meeting Representatives from clinical laboratories, infectious disease prevention, pharmacy, hospital epidemiology, academia
1 2 AR/AMS Multidisciplinary Advisory Group In-person quarterly meetings and follow up discussions Activities: Selection of antibiotics included in susceptibility testing panels Drafting test result language Establishing criteria for teared response https://www.cdc.gov/hai/outbreaks/docs/he alth-response-contain-mdro.pdf
Susceptibility Testing Panels Before
Susceptibility Testing Panels After
1 5 Testing of Carbapenemase Genetic Markers Beginning January 2017, specimen submission to the SPHL and/or our ARLN is required for genetic characterization Perform testing on all CRE submitted in accordance with laboratory reporting requirements Additional characterization of isolates with discordant results will be coordinated with support from ARLN Regional Lab and the CDC SPHL
Testing Panel Developed a lab panel at the SPHL to complement testing completed at local clinical labs Confirmation of organism identification Expanded antimicrobial susceptibility testing using Sensititre broth microdilution and disk diffusion Phenotypic characterization of carbapenemase production using the Modified Carbapenem Inactivation Method (mcim) CRE identification of five common carbapenemase enzymes by PCR: NDM OXA-48 VIM IMP KPC 1 6
Testing Panel Results Phenotypic characterization of carbapenemase mcim Test N=113 Percent Positive 40 35.4 Negative 73 64.6 Identification of carbapenemase enzymes by PCR N=40 Positive Number Percent KPC 31 77.5 NDM* 4 10.0 Oxa-48* 3 7.5 Not detected 2 5.0 *One person was NDM and Oxa-48 positive
Non-carbapenemase Screening Included for All CRE Isolates Mechanism of Action Under Investigation Molecular Class Mobilized Colistin Resistance PCR Target mcr-1 Antibiotic Class(es) directly affected* polymyxins *Other resistance mechanisms may be present on the same plasmid with carbapenemase genes mcr-1 N=113 Percent Negative 113 100
Expanded Reporting of Carbapenem Resistance Addition of carbapenem-resistant Acinetobacter baumanii (CRAB) ARLN Alerts ALERT! ALERT! ARLN Alerts N=17 Non-KPC CRE 1 9 CR-AB, Oxa-23 2 5 CR-AB, KPC 1 mcim+/pcr- 2 1 Eight unique individuals 2 Three unique individuals
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ARLN Alert and CP-CRE Follow-up Contact the healthcare facility which reported the case: Epidemiology Medical history Healthcare exposures in the past year Any interventions implemented International travel in the past year Flag the patient in the hospital system Contact and notify other healthcare providers Was the patient placed on contact precautions?
2 2 CRE Rectal Swab Colonization Testing through ARLN Regional Laboratory Cepheid GeneXpert bla KPC bla IMP-1 group bla VIM bla NDM OXA-48-like genes
Next Steps Testing for additional resistance mechanisms Addition of carbapenem-resistant Pseudomonas aeruginosa (CR-PA)
Acknowledgements CT DPH Meghan Maloney, MPH Vivian Leung, MD Erin Grogan, RN, MS Richard Melchreit, MD Lynn Sosa, MD Matt Cartter, MD State Public Health Laboratory Jafar Razeq, Ph.D. Anthony Muyombwe, Ph.D. Diane Noel, BS, MT Bobbie Macierowski, MS, M(ASCP) AR/AMS Multidisciplinary Advisory Group ARLN Partners in Wadsworth, NYS Centers for Disease Control and Prevention 24
Thank you Questions or Comments? noelisa.montero@ct.gov 25 25