A stewards guide to Verigene optimization Jason M. Pogue, PharmD, BCPS, BCIDP Clinical Pharmacist, Infectious Diseases Sinai-Grace Hospital; Detroit Medical Center Clinical Assistant Professor of Medicine Wayne State University School of Medicine

Objectives List the organisms and resistance mechanisms that are detected by Verigene BC-GP and BC-GN Discuss strategies for optimizing the use of Verigene within your institution

What is Verigene? Multiplex PCR test that is run on positive blood cultures Once blood culture turns positive Gram stain Place sample on BC-GP or BC-GN based on results Results in < 2.5 hours What do you get? Organism identification (most common ones) Key resistance determinants

Verigene BC- GP Species Genus Staphylococcus aureus Staphylococcus spp. Staphylococcus epidermidis Streptococcus spp. Staphylococcus lugdunensis Listeria spp. Streptococcus anginosus Group Streptococcus agalactiae Resistance determinants Streptococcus pneumoniae mec A Streptococcus pyogenes van A Enterococcus faecalis van B Enterococcus faecium

An example pathway for BC-GP

Verigene BC-GP: Impact Very straightforward and simple to put together a pathway based on results Impact on optimizing meaningful outcomes limited (time to appropriate therapy, LOS, mortality) Everyone gets vancomycin and it is active (even if not optimal) against most things Previous technologies that gave genus/species would lead to appropriate therapy as resistance predictable based off of it Even simple things like coagulase test, GPC in pairs and chains can drive to appropriate coverage if acted upon Time to optimal therapy can be improved Largely driven by quicker de-escalation off of vancomycin Impact on safety? Infect Control Hosp Epidemiol 2016;37:1361–1366; Proc (Bayl Univ Med Cent) 2015;28(2):139–143

Verigene BC- GN Species Resistance determinants Escherichia coli CTX-M Klebsiella pneumoniae KPC Klebsiella oxytoca VIM Pseudomonas aeruginosa IMP Genus NDM Acinetobacter spp. OXA Citrobacter spp. Enterobacter spp. Proteus spp. Can mean different things for different organisms A. baumannii  OXA-23, 51, 58 Enterobacteriaceae  OXA-48 like What it picks up versus what it doesn’t isn’t well defined….

Verigene BC-GN offers a HUGE opportunity to escalate and improve outcomes! Informal pathway at the DMC Organism detected Resistance determinant Regimen Enterobacteriaceae CTX-M Ertapenem KPC Meropenem/vaborbactam NDM-1/VIM/IMP Polymyxin B + ceftazidime/avibactam + aztreonam OXA Ceftazidime/avibactam Acinetobacter Polymyxin B + minocycline (usually) P. aeruginosa IMP/VIM Enterobacter, Citrobacter spp. Cefepime, piperacillin/tazobactam (if you are so inclined)

J Clin Microbiol. 2016 Jul;54(7):1789-1796

“Hospital length of stay was decreased in the post BC-GN group (7 (5-15) days versus 9 (4.5 – 21 days); p = 0.001)” Eur J Clin Microbiol Infect Dis. 2017 36(10):1879-1887

That’s great but…what do you do when resistance determinants are negative? Enterobacteriaceae There are non CTX-M ESBLs P. aeruginosa Common beta lactam resistance mechanisms not on that list A. baumannii Are all oxacillinases detected??

So what would you do? JJ is a 36 y/o female who presents with urosepsis. She has a history of recurrent UTI, no other details provided. Her vitals and relative lab values in the ED were as follows: BP: 97/60, Tmax 38.5, HR 110, RR 18 WBC 17.5, Creatinine 1.4 (baseline 0.8) Patient is started on Vancopime 17 hours later the following information comes back Blood culture GNR, Verigene (+) K. pneumoniae, resistance determinants negative No significant changes to the above labs, but patient stable on the floor ESBL rate at your institution in K. pneumoniae is 23% Who wants to (in addition to stopping vancomycin) A) Continue cefepime B) Escalate (kind of) to ertapenem C) De-escalate to ceftriaxone D) I do not know enough information to make this decision

Antimicrob Agents Chemother. 2018 Apr 26;62(5).

What did we learn? At both DMC and UMMC absence of key determinants largely rules out resistance to target agents One notable exception was P. aeruginosa Antibiogram and severity of illness should drive decisions And Ryan might have a solution for you in the next talk These data should NOT be used to justify a similar pathway at your institution But you can (and should) do the same thing

There are a few quirks of Verigene BC-GN to be aware of Off panel organisms From time to time we will see off panel organisms Common considerations: Serratia, Morganella, or in the right population Stenotrophomonas Also, if anaerobic culture only or GI source – think anaerobes Polymicrobial GN infections limitations Dominant organism might only be detected Different pathogen in untested bottle Impact on care limited (but not zero)

Summary/conclusion Verigene offers organism ID and the presence/absence of key resistance determinants ~48 hours prior to traditional methodology Impact on Gram positive BSI is modest Real benefit is in GNR Decrease time to appropriate therapy in resistant organisms Can also allow more rapid de-escalation (or spare unnecessary escalation) But clinical judgement warranted We do not have a pathway, even though usually feel comfortable given numbers (even with poly issue). Clinical situation (and other risk factors) need assessed

A stewards guide to Verigene optimization Jason M. Pogue, PharmD, BCPS, BCIDP Clinical Pharmacist, Infectious Diseases Sinai-Grace Hospital; Detroit Medical Center Clinical Assistant Professor of Medicine Wayne State University School of Medicine