Objectives - ProCE

1 SIDP Antimicrobial Stewardship Certificate Program Antimicrobial Stewardship and Microbiology: Focus on Rapid Diagnostic Tests1 Antimicrobial Stewardship Certificate ProgramAntimicrobial Stewardship and Microbiology: FRid Diti T tFocus on Rapid Diagnostic TestsKarri A. Bauer, PharmD, BCPS (AQ-ID)Specialty Practice Pharmacist Infectious DiseasesThe Ohio State University Wexner Medical Center1 Objectives Discuss the various rapid diagnostic technologies Evaluate the use of rapid diagnostic technologies Evaluate the use of rapid diagnostic technologies on patient outcomes Determine considerations during the preimplementation, implementation, and postimplementation phases of rapid diagnostic technologies2 SIDP Antimicrobial Stewardship Certificate Program Antimicrobial Stewardship and Microbiology: Focus on Rapid Diagnostic Tests2 Patient Case 62 year old male presented to the ED with cc of night sweats HPI: 3 day history of generalized fatigue fevers HPI: 3 day history of generalized fatigue, fevers and night sweats and nausea PMH: HTN, HLD, DM2 Physician Exam: Vitals.

2 Temp F, HR 110, BP 120/70, RR 20, 98% on RA398% on RA Blood cultures obtained prior to initiation of vancomycin + piperacillin/tazobactamGeneral Principles Basic Microbiology Direct examination Culture/Gram stain Culture/Gram stain Rapid biochemical tests Antibody and antigen detection Average time to deliver antimicrobial susceptibility testing results to a physician is 40 hours Numerous studies have demonstrated the impact of inappropriate antimicrobial therapy on mortality Kerremans JJ, Verboom P, Stijnen T, et al. Rapid identification and antimicrobial susceptibility testing reduce antibiotic use and accelerate pathogen-directed antibiotic use. J. Antimicrob Chemother2008;61 Antimicrobial Stewardship Certificate Program Antimicrobial Stewardship and Microbiology: Focus on Rapid Diagnostic Tests3 Dilemma with Conventional MethodsDay 0 Day 1 Day 2 Day 3 Day 4 Gram stain provides limited information.

3 Cannot tell the speciesEmpiric RxBroad-spectrum RxTargeted RxConventional DxPositiveBlood CultureGram StainConventional Species IDBlood Draw Culture is too slow Clinicians can t wait an additional 1-3 days to treat the infection Leads to inappropriate and ineffective therapy for some patients and unnecessarily therapy for othersIntroduction New advances in RDTs provide collaborative opportunities for antimicrobial stewardship programs (ASPs)programs (ASPs) Enhance functions of clinical microbiology laboratories Provide accurate organism identification Timely antimicrobial susceptibility testing data RDTs benefit the individual patient but also pincrease the effectiveness of ASPsSIDP Antimicrobial Stewardship Certificate Program Antimicrobial Stewardship and Microbiology: Focus on Rapid Diagnostic Tests4 Day 0 Day 1 Day 2 Day 3 Day 4 Conventional/New TimelineEmpiric RxBroad-spectrum RxTargeted RxConventional DxPositiveBlood CultureGram StainConventional Species IDBlood DrawPositive Rapid and accurate results on day 1 PositiveBlood CultureBlood DrawSpecies IDTargeted RxEmpiric RxGram Stain Supports decisions for appropriate and targeted therapy 1-3 days earlier than conventional methodsRapid Diagnostic TechnologiesSIDP Antimicrobial Stewardship Certificate Program Antimicrobial Stewardship and Microbiology.

4 Focus on Rapid Diagnostic Tests5 Polymerase Chain Reaction (PCR) Fluorescently labeled probe with primers Amplify target DNAC bilifi tid d t tii t 1 Combines amplification and detection into 1 process Roche Molecular System s LightCycler SeptiFastMecA BD GeneOhm s Cdiff assay Cepheid s C. difficileassayMultiplex PCR Fluorescently labeled prove with > 1 set of primers Simultaneous detection of multiple organisms Simultaneous detection of multiple organisms and resistant makers BD GeneOhm s Staph SR assay Cepheid s Xpert MRSA/SA blood culture and assays BioFire Diagnostics FilmArraySIDP Antimicrobial Stewardship Certificate Program Antimicrobial Stewardship and Microbiology: Focus on Rapid Diagnostic Tests6 Nanoparticle Probe Nucleic acid extraction and PCR amplification Hybridization of target DNA to capture oligonucleotides on a microarrayoligonucleotides on a microarray Signal amplification of hybridized probes provides an automated analysis Nanosphere s Verigene blood culture Gram-positive and Gram-negativeVerigene Gram Positive Blood Culture (BC-GP) TestAvailable Test PanelsSpeciesGenusSpeciesGenusStaphyloco ccus aureusStaphylococcus epidermidisStreptococcus lugdunensisMicrococcus anginosusListeria spp.

5 Streptococcus agalactiaeResistanceStreptococcus pneumoniaemecAStreptococcus pyogenesvanAEnterococcus faecalisvanBEnterococcus faeciumSIDP Antimicrobial Stewardship Certificate Program Antimicrobial Stewardship and Microbiology: Focus on Rapid Diagnostic Tests7 Verigene Gram Negative Blood Culture (BC-GN) TestAvailable Test PanelsSpeciesGenusSpeciesGenusEscherichi a coliAcinetobacter pneumoniaeCitrobacter oxytocaEnterobacter aeruginosaProteus Blood Culture Identification PanelAvailable Test PanelsGram-PositiveGram-NegativeEnteroco ccusAcinetobacter baumanniiListeria monocytogenesHaemophilus influenzaeStaphylococcus aureusNeisseria meningitidisStreptococcus agalactiaePseudomonas aeruginosaStreptococcus pneumoniaeEnterobacter cloacaeStreptococcus pyogenesEscherichia coliStreptococcus pyogenesKlebsiella oxytocaEnterococcus faecalisKlebsiella pneumoniaeEnterococcus faeciumProteus marcescensSIDP Antimicrobial Stewardship Certificate Program Antimicrobial Stewardship and Microbiology.

6 Focus on Rapid Diagnostic Tests8 Peptide Nucleic Acid Fluorescent In Situ Hybridization (PNA FISH) Synthetic oligonucleotide fluorescence-labeled probes Neutral charge of the synthetic molecule allows rapid Neutral charge of the synthetic molecule allows rapid hybridization to species-specific ribosomal RNA Fluorescence is detected using a fluorescence microscope QuickFISH (AdvanDx) Requires less setup timeqp Faster turnaround time 90 minutes-20 minutes from positive blood culturesPNA FISHS. aureus Coagulase-negative staphNegativeSIDP Antimicrobial Stewardship Certificate Program Antimicrobial Stewardship and Microbiology: Focus on Rapid Diagnostic Tests9 Matrix-Assisted Laser Desorption-Ionization Time-of Flight Mass Spectrometry (MALDI-TOF) Mass spectrometry results in ionization and disintegration of a target moleculedisintegration of a target molecule Mass/charge ratio of the resulting fragments is analyzed to produce a molecular signature Provides a profile or fingerprint of the organism Analyze thousands of samples/day from a variety of sourcesyRidDitiThlidRapid DiagnosticTechnologies andAntimicrobial StewardshipSIDP Antimicrobial Stewardship Certificate Program Antimicrobial Stewardship and Microbiology: Focus on Rapid Diagnostic Tests10 Staphylococcus aureus S.

7 Aureusinfections constitute a tremendous burden Saureusbacteremia requires prompt requires prompt microbiological diagnosis and antibiotic administration Vancomycin is often used empirically Use of antistaphylococcal -lactams have demonstrated superior clinical outcomesdemonstrated superior clinical outcomes compared to vancomycin for MSSA infectionsAvailable RDTsOrganismDetection time, hTechnologyManufacturerBatchingCLIAD esignationTrade NameSA, , Culture Colony TestS. , ratedBinaxNOWS. aureusMSSA, MRSA20-26 Chromogenic mediumBDNoHighBBLCHROM agarMRSA IIMRSA2 PCRR oche DiagnosticsYesHighLightCyclerMRSAMSSA, 2 Multiplex PCRBD GeneOhmYesHighBD GeneOhmMRSA, CoNSgStaph SRMSSA, MRSA, CoNS1 Multiplex PCRC epheidNoModerateXpertMRSA/SA BCS.

8 Aureus, MS and FilmArray can also be Antimicrobial Stewardship Certificate Program Antimicrobial Stewardship and Microbiology: Focus on Rapid Diagnostic Tests11mecAGene Testing and InterventionCarver PL, Lin S-W, DePestel DD, et al. Impact of mecAgene testing and intervention by infectious diseases clinical pharmacists on time to optimal antimicrobial therapy for Staphylococcus aureusbacteremia at a university hospital. JClin Micro2008;46 Therapy for Patients with MSSA BacteremiaParta M, Goebel M, Thomas J, et al. Impact of an assay that enables rapid determination of Staphylococcusspecies and their drug susceptibility on the treatment of patients with positive blood culture results. Infect Control HospEpidemiol2010;31(10) Antimicrobial Stewardship Certificate Program Antimicrobial Stewardship and Microbiology: Focus on Rapid Diagnostic Tests12 Time to Antibiotic KA, West JE, Balada-Llasat JM, et al.

9 An antimicrobial stewardship program s impact with rapid polymerase chain reaction methicillin Staphylococcus aureus/S. aureusblood culture in patients with S. aureusbacteremia. ClinInfect Dis2010;51(9):1074-1080. RDT and Stewardship Intervention-Hospital Costs$69,73770 00080,000$48,35030,00040,00050,00060,000 70,000p= ,00020,000 PreinterventionPostinterventionBauer KA, West JE, Balada-Llasat JM, et al. An antimicrobial stewardship program s impact with rapid polymerase chain reaction methicillin Staphylococcus aureus/S. aureusblood culture in patients with S. aureusbacteremia. ClinInfect Dis2010;51(9):1074-1080. SIDP Antimicrobial Stewardship Certificate Program Antimicrobial Stewardship and Microbiology: Focus on Rapid Diagnostic Tests13 Coagulase-Negative Staphylococci spp. Often considered a contaminant Multiple positive blood cultures require therapy Clinicians often determine the positive blood cultures to represent contaminationASP PharmD Interventions for CoNS Using Rapid PCRP reinterventionPostinterventionPDiscontin uation of antistaphyloccalantibiotics, antibiotic exposure, LOS, costs$28,973$20, vancomycin7 (21%)Wong JR, Bauer KA, Mangino JE, Goff DA.

10 Antimicrobial stewardship pharmacist interventions for coagulase-negative staphylococci positive blood cultures using rapid polymerase chain reaction. Ann Pharmacother2012; 46(11): Antimicrobial Stewardship Certificate Program Antimicrobial Stewardship and Microbiology: Focus on Rapid Diagnostic Tests14 Assessment of PNA FISH CoNS in the Absence of Stewardship InterventionHoltzman C, Whitney D, Barlam T, et al. Assessment of impact of peptide nucleic acid fluorescence in situhybridization of rapid identification of coagulase-negative staphylococci in the absence of antimicrobial stewardship intervention. J Clin Micro 2011;49(4) spp. 3rdmost commonly isolated healthcare-associated organism Intrinsically resistant to many antibiotics May acquire additional resistant determinants VRE bacteremia associated with suboptimal patient outcomes Empiric therapy includes vancomycin, ppyy,daptomycin, or linezolidSIDP Antimicrobial Stewardship Certificate Program Antimicrobial Stewardship and Microbiology: Focus on Rapid Diagnostic Tests15 Available RDTsOrganismDetectioTechnologyManufactur BatchinCLSIT radeOrganismDetection time, hTechnologyManufacturerBatchingCLSID esignationTradeNameE.