MDRO and nMDRO: A Briefing for Clinical and Public Health - PowerPoint PPT Presentation

Analysis. A Answers. s. Action. www.aphl.org MDRO and nMDRO: A Briefing for Clinical and Public Health Microbiologists September 19, 2019 Speaker: Janet Hindler Moderator: Paula Snippes-Vignone Information, tools, and references used in this program reflect the opinion of the presenter and are not recommendations or requirements endorsed by the LA County Department of Public Health or Association of Public Health Laboratories.

At the conclusion of this program, you will be able to: ♦ Discuss the definitions for MDRO and novel MDRO (nMDRO). ♦ List MDRO that currently represent the greatest threats to healthcare facilities and the community. ♦ Describe laboratory responsibilities for detecting and reporting MDRO. 2

Check separate reference list provided with this webinar! https://clsi.org/standards/products/free- resources/access-our-free-resources/

Specimen: Blood Diagnosis: Pyelonephritis E. coli amikacin S ampicillin R Infection preventionist cefazolin R wants to know if this ceftriaxone R is an MDRO… ciprofloxacin R ertapenem S Is it?? gentamicin S meropenem S piper-tazo R tobramycin S trimeth-sulfa R 4

Resistance Concepts and MDRO 5

Intrinsic “R” • Naturally occurring or innate or normal “R” that a bacterium possesses to an antimicrobial agent(s) • Representative of all or almost all (>99%) isolates of a genus or species CLSI M100 29 th ed “Intrinsic R Tables” Never report “S” for agent to which the organism has intrinsic “R” 6 ..report “R” or suppress

Intrinsic “R” Acquired “R” • Naturally occurring or innate • A bacterium that was or normal “R” that a previously “S” can become bacterium possesses to an “R” as a result of antimicrobial agent(s) • Spontaneous gene • Representative of all or mutation and selection almost all (>99%) isolates of a • Acquisition of R genes genus or species from another bacterium (same or different species) “R” gene on plasmid • Example: CLSI M100 29 th ed “Intrinsic R Tables” KPC gene from K. pneumoniae to Never report “S” for agent to which E. coli and S. marcescens the organism has intrinsic “R” Sidjabat et al. 2009. Clin Infect Dis. 49:1736. ..report “R” or suppress 7

Wild Type (Normal) Profiles (R = intrinsic Resistance) Enterobacter Pseudomonas Acinetobacter Stenotrophomonas Agent E. coli cloacae aeruginosa baumannii maltophilia amikacin S S S S R ampicillin S R R R R cefazolin S R R R R cefepime S S S S S ceftriaxone S S R S R ciprofloxacin S S S S S ertapenem S S R R R gentamicin S S S S R meropenem S S S S R pip-tazo S S S S R tobramycin S S S S R trim-sulfa S S R S S Must know when and how to detect acquired “R” 8

MDRO - Definitions 9

What are MDRO? • No universal comprehensive definition or single list of MDRO! • Resistant to one key drug (e.g., MRSA, VRE) • Resistant to one or more drugs from several drug classes • Harbor specific “R” genes (e.g., mecA, KPC ) 10

What are MDRO? Why are MDRO a big deal? • No universal • Treatment options limited comprehensive definition or • MDRO infections are single list of MDRO! associated with increased • Resistant to one key drug lengths of stay, costs, and (e.g., MRSA, VRE) OR mortality • Resistant to one or more • Significant challenge for drugs from several drug infection preventionists and classes public health professionals • Harbor specific “R” genes • Must minimize spread! (e.g., mecA, KPC ) MDROs are important from treatment and infection prevention perspectives! 11

2012 Global Effort to Standardize Definitions ♦ MDR – multidrug-R (e.g., “not susceptible” to at least 1 drug in ≥ 3 drug classes) ♦ XDR – extensively drug-R (e.g., “not susceptible” to almost all classes but retains “S” to at least one drug class) ♦ PDR – pandrug-R (e.g., “R” to all drugs available) • Definitions apply to “acquired” (vs. “intrinsic”) resistance and to drugs that might be used to treat an infection caused by the species. • Limitation – based on testing nearly all available antimicrobial agents. Magiorakos et al. 2012. Clin Microbiol & Infection. 18:268-281. 12

Provides data about healthcare-associated infections (HAIs) including those caused by antibiotic resistant bacteria. [as reported through CDC’s National Health Safety Network (NHSN)] Includes “Phenotype Definitions” of MDR CDC’s Antibiotic Resistance Patient Safety Atlas

For MDRO definition, should we use “Resistant” or “Not Susceptible” interpretation? ♦ Resistant ♦ Not Susceptible includes: – Resistant – “Intermediate (I)” – “Susceptible Dose Dependent (SDD)” MIC (µg/ml) Organism Group S I SDD R ≤4 ≥16 Enterobacteriaceae - gentamicin 8 - ≤2 ≥16 Enterobacteriaceae - cefepime - 4-8 14

MDRO Enterobacteriaceae Definition Antimicrobial Groups “R” to at least 1 drug in at Tobramycin (not Serratia) OR least 3 or 4 of the 6 gentamicin antimicrobial groups Piperacillin-tazobactam Imipenem (not Proteus) OR Based on drugs commonly meropenem tested in clinical labs! Cefotaxime OR ceftriaxone OR ..also have XDRO definition for ceftazidime Enterobacteriaceae Ciprofloxacin Trimeth-sulfamethoxazole Adapted from : Canadian recommendations for laboratory interpretation of MDR GNR; German, GJ et al. 2018. Can Commun Dis Rep. 44:29-34. 15

XDRO Pseudomonas aeruginosa Acinetobacter spp. Definition Antimicrobial Groups “R” to at least 1 drug in all 5 Ciprofloxacin antimicrobial groups Piperacillin-tazobactam Ceftazidime No MDRO definition…only XDRO definition for P. Imipenem OR meropenem aeruginosa and Acinetobacter Tobramycin Adapted from : Canadian recommendations for laboratory interpretation of MDR GNR; German, GJ et al. 2018. Can Commun Dis Rep. 44:29-34. 16

Practical List MDRO ♦ MRSA (and VISA, VRSA) ♦ VRE ♦ GNR resistant to all drugs on panel ♦ GNR resistant to all drugs on panel except carbapenems ♦ Extended-spectrum cephalosporin-R E. coli, Klebsiella, Proteus mirabilis (ESBL and ampC phenotype) ♦ Carbapenem-R GNR – Enterobacteriaceae (CRE) – P. aeruginosa (CRPA) – Acinetobacter (CRAB) ♦ Candida auris ♦ S. pneumoniae (penicillin-R in LTCF) ♦ Neisseria gonorrhoeae – extended-spectrum cephalosporin, nonsusceptible 17

Novel MDRO (nMDRO) ♦ Rare or uncommon to region ♦ Pan-R isolates – Very rare in USA Los Angeles County nMDRO ♦ Suspect Pan-R isolates – “Not susceptible” to all drugs on the clinical lab’s panel ♦ Rare carbapenemases, e.g. – P. aeruginosa VIM, IMP – K. pneumoniae NDM ♦ Candida auris ♦ VISA / VRSA 18

An nMDRO LA County LA Hospital Story Public Health Lab Public Health Epidemiologist CRPA VIM + IMP Positive isolated by PCR Infection CRPA #2 Preventionist Outbreak Investigation: isolated Oh my!! • PH epidemiologist visited hospital • Noted excellent infection prevention practices (enhanced after 1 st nMDRO confirmed) • No additional cases! 19 CRPA, carbapenem-resistant P. aeruginosa

Los Angeles County Carbapenemase-Producing Species* *Isolates submitted from clinical laboratories that were positive for “big 5” carbapenemases 2015-2019 (N=1589) 20

Los Angeles County Carbapenemase Distribution* Big 5….. KPC NDM VIM IMP OXA *Isolates submitted from clinical laboratories that were positive for “big 5” carbapenemases 2015-2019 (N=1589) 21

Pseudomonas aeruginosa An nMDRO Story VIM + IMP positive MIC (µg/ml) amikacin >32 R aztreonam 8 S VIM IMP cefepime >16 R ceftazidime >16 R ceftolozane- Metallo beta-lactamases tazobactam >256/4 ciprofloxacin >2 R colistin 2 S gentamicin >8 R meropenem >8 R piper-tazo 32 I tobramycin >8 R 22

Why are we concerned about Candida auris? ♦ MDRO – Some resistant to all 3 antifungal classes – Approximately 90% are resistant to fluconazole and 30% to amphotericin B (unpublished data, CDC) ♦ Causes outbreaks in healthcare settings – Colonizes skin and healthcare environments in contrast to other Candida spp. Can be misidentified as Candida haemulonii or other Candida spp . Google CDC Candida auris – many resources! 23

Clinical cases of Candida auris reported by U.S. states, as of July 31, 2019 24 https://www.cdc.gov/fungal/candida-auris/tracking-c-auris.html

CLSI and Testing/Reporting of MDRO 25

CLSI is addressing MDRO by… ♦ Providing guidance for: – Selective reporting (suppression) of antimicrobial agents – Testing / reporting supplemental agents on MDRO – Confirming uncommon results – Detection of resistance mechanisms (e.g., ESBL, carbapenemases), when needed for epidemiology ♦ Reassessing breakpoints to ensure “clinical” resistance and susceptibility are reliably detected ♦ Providing guidance for preparation of cumulative antibiograms (CLSI M39-A4 document) 26

What does CLSI say about MDRO? Section I.D. Selective Reporting 1 “Selective reporting should improve the clinical relevance of test reports and help minimize the selection of multiresistant strains by overuse of broad-spectrum agents.” Always report unexpected resistance! 1 report broad-spectrum agents only when isolate is resistant to narrower-spectrum agents CLSI M100 29 h ed “Instructions for Use” 27