Antimicrobial Stewardship & Microbiology: Focus On Rapid Diagnostic Tests

SIDP – Antimicrobial Stewardship Certificate Program
Antimicrobial Stewardship & Microbiology: Focus on Rapid Diagnostic Tests
Antimicrobial Stewardship & Microbiology:

Focus on Rapid Diagnostic Tests
Monica V. Mahoney, PharmD, BCPS AQ-ID, BCIDP

Clinical Pharmacy Coordinator, Infectious Diseases
mgolik@bidmc.harvard.edu
Objectives:
• Discuss the various rapid diagnostic technologies
• Evaluate the use of rapid diagnostic technologies
on patient outcomes
• Determine considerations during the pre-
implementation, implementation, and post-
implementation phases of rapid diagnostic
technologies
1
Patient Case
• 54 y/o male seen at PCP’s office for 2 week h/o
fever, weakness, and malaise
• PMH: DM, HTN, known murmur
• Vitals: T 101.8˚F, HR 110, BP 88/60 mmHg,
RR 18, 98% RA
• Concern for infection. PCP draws blood cultures
and directly admits for workup
• What antibiotics do you recommend?
Selecting Antimicrobial Therapy
Targeted antimicrobial therapy
Antimicrobial susceptibilities available
Organism identification
Gram stain
24 h 48 h 72 h 96 h
Empiric Rx Broad Rx Directed Rx
2
Sepsis, Antibiotics, & Mortality – Oh My!
Kumar et al. Crit Care Med 2006;34:1589-96
Patient Case
• 54 y/o male seen at PCP’s office for 2 week h/o fever,
weakness, and malaise
• PMH: DM, HTN, known murmur
• Vitals: T 101.8˚F, HR 110, BP 88/60 mmHg,
RR 18, 98% RA
• Concern for infection. PCP draws blood cultures and
directly admits for workup
• Started on: piperacillin/tazobactam & vancomycin
3
Patient Case: Cultures Day 1
Started on: piperacillin/tazobactam & vancomycin
Discontinued: piperacillin/tazobactam
Continued on: vancomycin
4
Changed to: ampicillin & ceftriaxone
Selecting Antimicrobial Therapy
Gram stain
24 h 48 h 72 h 96 h
Empiric Rx Broad Rx Directed Rx
Piperacillin/tazobactam Vancomycin Ampicillin & Ceftriaxone
& Vancomycin
5
Rapid Diagnostic Technologies

• Obtain blood sample
• Bypass the need to traditionally grow in culture
• Bottle flagged for growth
• Test for bacterial components

• Some with the ability to provide susceptibility
results
Benefit of RDTs
Gram stain
Traditional Cultures
24 h 48 h 72 h 96 h
MR MALD
I TOF
PNA FISH
Rapid Diagnostics
PCR & mPCR
MR: magnetic resonance; MALDI TOF: Matrix-assisted laser desorption ionization – time of flight; PNA FISH: Peptide nucleic acid fluorescence
in situ hybridization; PCR: polymerase chain reaction; mPCR: multiplex PCR
6
IDSA Stewardship Guidelines
Barlam TF et al. Clin Infect Dis 2016;62:e51-e77
Pharmacist Survey
Foster RA. Infect Control Hosp Epi 2017
7
Recipients of RDT Results

Respondents
ASP: antimicrobial stewardship program; R/F: resident/fellow
Pharmacist Survey
• Conclusions:
• Pharmacists are frequently contacted with RDT results
• Completion of formalized ID training (residency / fellowship)
significantly increased self-reported familiarity with RDT
• Availability of ID-trained pharmacists?
∴ RDT education should be wide-spread
8
Benefit of RDTs
Gram stain
24 h 48 h 72 h 96 h
MR MALDI
TOF
PNA FISH
Rapid Diagnostics
PCR & mPCR
Traditional Methods
9
Gram Negative Organisms
Gram Negative Organisms
Susceptible Moderate Resistant
10
Benefit of RDTs
Gram stain
24 h 48 h 72 h 96 h
MR MALDI
TOF
PNA FISH
Rapid Diagnostics
PCR & mPCR
MALDI-TOF MS
Matrix-assisted laser desorption ionization – time of flight
(MALDI-TOF) mass spectrometry (MS)
11
MALDI-TOF MS
• Mass spectrometry results in ionization and disintegration of
a target molecule
• Mass/charge ratio of the resulting fragments is analyzed to
produce a molecular signature
• Organism profile/fingerprint
• Analyze thousands of samples

per day from a variety of
sources
http://www.sigmaaldrich.com/technical-documents/articles/biology/custom-dna-oligos-qc-analysis-by-mass-spectrometry.html
MALDI-TOF MS Output
Slide courtesy of BioMériux
12
MALDI TOF MS Output
Adapted slide courtesy of BioMériux
MALDI-TOF MS in Real Life

Citation Intervention BSI Type Outcomes
Huang RDT alone vs. RDT plus real- Gram positive, Gram • ↓ time to ID by 28.1h
2013 time stewardship alerts negative, & fungal BSI • ↓ time to effective abx by 9.7h
• ↓ time to optimal therapy by 43h
• ↓ 30d all-cause mortality by 7.6%
Lockwood CDS (traditional cultures) vs. Gram negative BSI • ↓ time to ID by 25.5h
2016 RDT plus CDS plus real-time • ↓ time to susceptibility report by 26h
pharmacist alerts • ↓ time to therapy adjustment by 41h
• $3,411 saved per patient
*community hospitals
Beganovic RDT alone vs. RDT plus real- Gram positive & Gram • ↓ time to optimal therapy by 32.1h
2017 time stewardship alerts negative BSI • ↓ hospital LOS by 6d
• ↓ ICU LOS by 4.4 days (GNR only)
• $12,893 saved per patient ($6.3 million
annually)
RDT: rapid diagnostic technology; BSI: bloodstream infection; Abx: antibiotics; CDS: computerized decision support; GNR: Gram-negative rod
Huang AM. Clin Infect Dis 2013;57:1237-45

Lockwood AM. Infect Control Hosp Epidemiol 2016;37:425-32
Beganovic M. J Clin Microbiol 2017;55:1347-45
13
MALDI-TOF MS
Advantages Disadvantages
• Can identify many • High upfront cost
different bacteria and • Requires pure colony
fungi • Lysing kits may allow
• Not specific to a certain detection directly from
specimen positive blood culture
• Very easy to set up and • No susceptibility /
quick to run resistance information
Slide courtesy of Brandon Dionne, PharmD
MALDI-TOF MS Caution
Bacteriapedia
Casereportitis
14
Benefit of RDTs
Gram stain
24 h 48 h 72 h 96 h
MR MALDI
TOF
PNA FISH
Rapid Diagnostics
PCR & mPCR
PNA FISH
Peptide nucleic acid fluorescence in situ hybridization
15
PNA FISH
• Synthetic oligonucleotide fluorescence-labeled probes
for species-specific ribosomal RNA
• Can detect select Gram positive, Gram negative, and
yeasts in 20 minutes
• Reagents selected based on Gram stain
• Can detect polymicrobial infections
http://www.opgen.com/pathogenid/pna-fish-products/
PNA FISH (aka traffic light)
Staphylococcus Gram negative rods
Enterococcus Candida
http://www.opgen.com/pathogenid/quickfish-products/
16
PNA FISH in Real Life

Forrest Routine culture vs. RDT CoNS • Not significant ↓ 1.88 DDD vancomycin use
2006 plus real-time • ↓ LOS by 2 days (non-ICU group)
stewardship alerts • $4000 saved per patient
Forrest Routine culture vs. RDT Enterococcus • ↓ time to ID by 2.6d
2008 plus real-time • ↓ time to appropriate therapy by 1.8d (VRE)
stewardship alerts plus • ↓ 30d mortality by 17% (VRE)
treatment algorithm
Heil Routine culture vs. RDT Candida • ↓ time to ID by 3.8d
2012 plus real-time • ↓ time to targeted therapy by 2d
pharmacist alerts plus • $415 saved per patient
treatment algorithm
RDT: rapid diagnostic technology; CoNS: coagulase negative Staphylococcus; DDD: defined daily dose; LOS: Length of stay; ICU: intensive care
unit; VRE: vancomycin-resistant enterococci
Forrest GN. J Antimicrob Chemother 2006;58:154-8

Forrest GN. Antimicrob Ag Chemother 2008;52:3558-63
Heil EL. Am J Health-Syst Pharm 2012;69:1910-4
PNA FISH
• Relatively inexpensive • More hands-on time for
• Quick turnaround micro lab
directly from positive • No batching
blood culture • Limited in number of
species detection
• No susceptibility /
resistance data
17
Automated FISH/Imaging
• Accelerate Pheno
• PhenoTest BC: 5 Gram (+), 7 Gram (-), & 2 Candida
• Combination of automated FISH and “morphocellular
kinetic analysis”
• Identifies organisms: uses fluorescence imaging
• Predicts susceptibility: uses growth curve algorithms
Willey BM, et al. Open Forum Infect Dis. 2017; 4(Suppl 1): S594–S595.
http://acceleratediagnostics.com/fda
18
PhenoTest Susceptibility
Erythromycin
Ciprofloxacin
Meropenem
Daptomycin
Vancomycin
Ceftazidime
Ceftriaxone
Tobramycin
Gentamicin
Ceftaroline
Aztreonam
Ertapenem
Amp/Sulb
Ampicillin
Cefepime
Amikacin
Linezolid
Pip/Tazo
S. aureus ✔ ✔ ✔ ✔ ✔
S. lugdunensis ✔
CoNS ✔ ✔
Enterococcus spp. ✔ ✔ ✔ ✔
Streptococcus spp. ✔ ✔ ✔
E.coli ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
Klebsiella spp. ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
Enterobacter spp. ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
Proteus spp. ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
Citrobacter spp. ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
S. marcescens ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
P. aeruginosa ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
A. baumannii ✔ ✔
PhenoTest Output
Photo courtesy of Katie Lusardi, PharmD
19
Automated FISH/Imaging in Real Life

Dare Routine culture vs. RDT Gram-positive & • ↓ time to appropriate therapy by 36h
2018 plus real-time Gram-negative • ↓ antibiotic duration of therapy by 2d
stewardship alerts • ↓ hospital LOS by 3d
RDT: rapid diagnostic technology; LOS: length of stay
Dare R. Patients IDWeek 2018. Poster 1758. Impact of Accelerate Pheno System…
• Identifies a larger • Sensitivity and specificity
number of pathogens may change with
compared to PNA FISH increased use
• Not limited to specific • Cost?
resistance genes
• Most rapid
susceptibility with MICs
MIC: minimum inhibitory concentration
20
Benefit of RDTs
Gram stain
24 h 48 h 72 h 96 h
MR MALDI
TOF
PNA FISH
Rapid Diagnostics
PCR & mPCR
PCR & mPCR

Polymerase chain reaction & multiplex PCR
21
PCR & mPCR

• A type of nucleic acid amplification test (NAAT)
• Fluorescently labeled probes with primers
• Detects targeted genetic material of pathogen
• Multiplex PCR (mPCR) can
detect multiple organisms
and/or resistance
mechanisms
https://www.thermofisher.com/ng/en/home/life-science/cloning/cloning-learning-center/invitrogen-school-of-molecular-biology/pcr-education/pcr-reagents-
enzymes/pcr-cycling-considerations.html
PCR Examples
• Xpert MRSA/SA BC
• StaphSR
Detection of S. aureus Detection of MRSA

Sensitivity Specificity Sensitivity Specificity
Xpert MRSA/SA BC 99.6% 99.5% 98.1% 99.6%
Staph SR 99.2% 96.5% 94.3% 97.8%
Buchan BW. J Clin Microbiol 2015;53:804-9
22
PCR in Real Life

Bauer Routine culture vs. RDT MRSA • ↓ time to ID by 1.6d
2010 plus real-time • ↓ time to appropriate therapy by 1.7d (MSSA)
stewardship & clinician • ↓ time to ID consultation by 6d
alerts • $21,387 saved per patient
Wong Routine culture vs. RDT CoNS • ↓ time to d/c therapy in contaminants by 32h†
2012 plus semi-real-time • ↓ hospital LOS by 4.5d†
stewardship alerts* • Non-significant $17,844 saved per patient†
RDT: rapid diagnostic technology; MRSA: methicillin-resistant Staphylococcus aureus; MSSA: methicillin-susceptible S. aureus; CONS: coagulase
negative Staphylococcus; LOS: length of stay
*Initially emailed a daily log, then converted to real-time pages + email log
†Terminated early due to manufacturing unavailability
Bauer KA. Clin Infect Dis 2010;51:1074-80

Wong JR. Ann Pharmacother 2012;46:1484-90
Multiplex Resistance Gene Comparison

Resistance Genes FilmArray Verigene PhenoTest
Gram-positive
mecA (MRSA) ✔ ✔
Cefoxitin screen (MRSA) ✔
MLSb (Erythromycin- ✔
Clindamycin)
vanA (VRE) ✔
vanB (VRE) ✔
vanA/B (VRE) ✔
Gram-negative
CTX-M (ESBL) ✔
IMP (carbapenemase) ✔
KPC (carbapenemase) ✔ ✔
NDM (carbapenemase) ✔
OXA (carbapenemase) ✔
VIM (carbapenemase) ✔
MRSA: methicillin-resistant S. aureus; VRE: vancomycin resistant enterococci; ESBL: extended spectrum beta-lactamase
23
Multiplex for Gram Positives

Pathogen FilmArray Verigene PhenoTest
Enterococcus ✔
E. faecalis ✔ ✔
E. faecium ✔ ✔
Staphylococcus ✔ ✔
S. aureus ✔ ✔ ✔
S. lugdunensis ✔ ✔
S. epidermidis ✔ ✔*
Streptococcus ✔ ✔ ✔
S. anginosus Group ✔
S. agalactiae (Group B) ✔ ✔ ✔
S. gallolyticus ✔
S. mitis ✔
S. oralis ✔
S. pneumoniae ✔ ✔ ✔
S. pyogenes (Group A) ✔ ✔
Listeria ✔ (L. monocytogenes) ✔
Micrococcus ✔
*S. capitis, S. epidermidis, S. haemolyticus, S. hominis, S. lugdunensis, S. warneri
Multiplex for Gram Negatives

Acinetobacter ✔ (A. baumannii) ✔ ✔ (A. baumannii)
Pseudomonas aeruginosa ✔ ✔ ✔
Neisseria meningitidis ✔
Haemophilus influenzae ✔
Enterobacteriaceae ✔
Citrobacter ✔ ✔ (C. freundii, C. koseri)
Enterobacter ✔ (E. cloacae complex) ✔ ✔ (E. cloacae, E. aerogenes)
Escherichia coli ✔ ✔ ✔
Klebsiella oxytoca ✔ ✔ ✔
Klebsiella pneumoniae ✔ ✔ ✔
Proteus ✔ ✔ ✔(P. mirabilis, P. vulgaris)

Serratia marcescens ✔ Not FDA-cleared ✔
24
Multiplex for Fungi

Candida
C. albicans ✔ ✔
C. glabrata ✔ ✔
C. krusei ✔
C. parapsilosis ✔
C. tropicalis ✔
FilmArray Output
Gram positive
Gram negative
Yeast
25
Verigene BC-GP Output
Slide courtesy of Luminex
mPCR in Real Life

Box 2015 Routine culture vs. Gram- • ↓ time to appropriate therapy by 20-30h (MSSA,
RDT plus real-time positive E. faecalis, & Streptococcus)
pharmacist alerts • ↓ time to d/c therapy for contaminants by 17.8h
community hospitals • ↓ hospital LOS by 1.9d
• $7,240 saved per patient
Walker Routine culture vs. Gram- • ↓ time to ID by 27h

2016 RDT plus real-time negative • ↓ time to appropriate therapy by 33.8h (ESBL)
clinician alerts • ↓ ICU LOS by 4.2d
• ↓ 30d mortality by 11.1%
Daily stewardship BSI • $11,661 saved per patient
log review
RDT: rapid diagnostic technology; MSSA: methicillin-susceptible S. aureus; LOS: length of stay; BSI: bloodstream infection; ESBL: extended
spectrum beta-lactamase; ICU: intensive care unit
Box MJ. Pharmacother 2015;35:269-76

Walker T. J Clin Micro 2016;54:1789-96
26
Verigene vs FilmArray
• Several studies comparing performance of the two systems

on monomicrobial bloodstream infections:
• Ward C. Performance evaluation of the Verigene (Nanosphere) and
FilmArray (BioFire) molecular assays for identification of causative
organisms in bacterial bloodstream infections. Eur J Clin Microbiol
Infect Dis 2015;34:487-96. 173 cultures.
• Bhatti MM. Evaluation of FilmArray and Verigene systems for rapid

identification of positive blood cultures. J Clin Microbiol.
2014;52:3433-6. 121 cultures.
PCR / mPCR
• Rapid turnaround with • Cost of hardware and panels
very little hands-on time is higher than many other
RDTs
• Detects most common
pathogens • No batching on Verigene
• Difficult to distinguish active
• Provides some resistance infection from
information colonization/previous
• Possible batching on PCR infection
& FilmArray • Cannot detect all
pathogens/resistance genes
• Other syndromic panels on panel
available
27
Benefit of RDTs
Gram stain
24 h 48 h 72 h 96 h
MR MALDI
TOF
PNA FISH
Rapid Diagnostics
PCR & mPCR
Magnetic Resonance
28
Magnetic Resonance
• T2Dx
• T2Candida panel (C. albicans, C. glabrata, C. krusei, C.
parapsilosis, C. tropicalis)
• T2Bacteria panel (S. aureus, E. faecium, E. coli, K.
pneumoniae, P. aeruginosa)
• Superparamagnetic particles bind pathogen 
changes in magnetic resonance signal
Mylonakis E, et al. Clin Infect Dis. 2015;60(6):892-9.

https://www.t2biosystems.com/t2direct-diagnostics/t2dx-instrument/
Magnetic Resonance in Real Life

Shields Routine culture plus T2 in Fungal • ↑ diagnosis of candidemia (7% to 14%)
2018 ICU patients at risk for • Discontinued therapy in 12/88 patients
candidiasis • ↓ antifungal duration of therapy by
11d/month
Gill 2018 Routine culture plus β-D- Fungal • ↑ discontinuation of therapy
glucan testing vs. routine • ↓ echinocandin duration by 1d
culture plus T2 in ICU
patients
ICU: intensive care unit
Shields RK. IDWeek 2018. Poster 2033. Incorporating T2Candida testing into routine…
Gill CM. IDWeek 2018. Poster 2043. T2-Candida (T2MR) versus Beta-D-Glucan (BDG)…
29
Magnetic Resonance
• VERY rapid results • Cost
• Low limit of detection • Clinical data still limited
• Fully automated • The gold standard reference
for sensitivity and specificity
is not clear
• Unclear what to do with
positive result but negative
blood culture
RDT without AST? Just Say No

AKA if you build it, they won’t come
Study Intervention Outcomes

Holtzman 2011 PNA FISH – CoNS • No difference in hospital LOS
• No difference in vancomycin use
Frye 2012 PCR – S. aureus/MRSA • Decreased organism identification time
• No difference in time to optimal abx
Cosgrove 2016 PNA FISH – streptococcal & • No difference in time to effective abx
enterococcal bacteremia • No difference in LOS
• No difference in in-hospital mortality
CoNS: coagulase negative Staphylococcus; LOS: length of stay; MRSA: methicillin-resistant S. aureus; abx: antibiotics
Holtzman C. J Clin Microbiol 2011;49:1581-2

Frye AM. J Clin Microbiol 2012;50:127-33
Cosgrove SE. Diagn Microbiol Infect Dis 2016;86:86-92
30
RDT with AST? Just Do It

Study Randomized Trial of Rapid Multiplex Polymerase Chain Reaction-Based Blood Culture
Identification and Susceptibility Testing
Intervention Prospective, RCT of patients with + blood cultures
• Standard blood culture processing
• Rapid multiplex PCR (rmPCR)
• rmPCR with real-time AST intervention
All rmPCR used computerized reports, templated comments, antibiogram-led therapy,
and institutional protocols.
Results Variable Standard rmPCR rmPCR/AS p value
Organism ID 22.3h 1.3h 1.3h < 0.001
Broad / Narrow Abx 56h / 42h 44h / 71h 45h / 85h 0.01 / 0.04
De-escalation / Escalation 34h / 24h 38h / 6h 21h / 5h < 0.001 / 0.04
Txt of contaminants 25% 11% 8% 0.015
No difference in mortality, length of stay, or cost
RCT: randomized control trial; AST: antimicrobial stewardship; Abx: antibiotics; Txt: treatment
Banerjee et al. Clin Infect Dis. 2015;61:1071-80
RDT with AST? Just Do It. Again.

Study Benefits of Adding a Rapid PCR-Based Blood Culture Identification Panel to an
Established Antimicrobial Stewardship Program
Intervention Pre-post, quasi-experimental study of patients with + blood cultures
• Standard organism identification (control)
• Standard identification plus AST intervention (AS)
• rmPCR plus AST intervention (BCID)
Results
Variable Control AS BCID p value
Organism ID 57h 54h 17h < 0.001
Time to Effective Txt 15h 13h 5h < 0.001
De-escalation 34% / 63h 57% / 61h 52% / 48h 0.034
No difference in mortality, 30-day readmission, ICU length of stay, post-culture length of

stay, or cost
AST: antimicrobial stewardship; Txt: treatment; ICU: intensive care unit
MacVane and Nolte. J Clin Microbiol. 2016;54:2455-63
31
Stewardship Guidelines
“First, ASP support or rapid notification of
results was a consistent feature of the studies
that found statistically significant associations
between rapid testing and outcomes …
Second, rapid testing should be performed
continuously (ie 24/7) or at least in frequent
batches.”
Barlam TF et al. Clin Infect Dis 2016;62:e51-e77
RDT with ID Fellows

Study The Effect of Rapid Diagnostic Testing with Infectious Diseases Fellow Consultative
Intervention on the Management of Enterococcal Bloodstream Infection
Intervention Retrospective study of patients with + E. faecalis and E. faecium blood cultures
• Standard organism identification (PNA FISH) (baseline)
• RDT (Verigene) identification with chart documentation (BC-GP)
• RDT with real-time ID fellow alert (BC-GP + ID)
Results Variable Baseline BC-GP BC-GP + ID p value
Time to IPT for E. faecium 16.1h 9.9h 5.5h 0.002 and 0.004*
Time to IPT for E. faecalis 55.8h 28.0h 28.3h NS

Length of stay 17d 12d 11d 0.04†
RDT: rapid diagnostic technology; IPT: institutional preferred therapy
*p values for BC-GP + ID vs. baseline and BC-GP + ID vs. BC-GP, respectively
†p value for BC-GP + ID vs. baseline
Gray ME. Diagn Microbiol Infect Dis 2018;92:319-24
32
If You Build It, They Won’t Come.

But If You Go Away, Will They Stay?
Baseline (7 mo) Intervention (7 mo) Post-Intervention (7 mo)

• 1° team notified • 1° team notified of + • 1° team notified of + blood
of + blood cx blood cx cx
• PNA FISH on BSI • Verigene done on BSI + GPC

• Verigene done on BSI +
+ GPC in chains GPC • No active AST notification or
recommendation
• AST notified via email or
CDS with susceptibilities
• AST contacted 1° team or
clinical RPh with recs
• Introduction of Verigene ↓ time to optimal therapy in select patients

• Removal of AST involvement – after several months of active intervention – resulted in sustained
results
BSI: bloodstream infection; GPC: Gram-positive cocci; Cx: culture; AST: antimicrobial stewardship; CDS: computerized decision support;
RPh: pharmacist
Avdic E. J Antimicrob Chemother 2017;72:3191-8
Time is Money!
Test Type Test Name Hands-On Time Result Turn Around Time*
MALDI-TOF MS MALDI-TOF MS 10-20 min 5 min
PNA FISH PNA FISH 10 min ≤ 90 min
QuickFISH ≤ 5 min 20 min
PhenoTest ≤ 5 min 1.3h to identification; 6.6h to susceptibilities
PCR GeneXpert ≤ 5 min ≤ 1h
GeneOhm ≤ 5 min < 2h
mPCR FilmArray ≤ 5 min 1h
Verigene ≤ 5 min < 3h
MR T2Candida ≤ 5 min < 5h from blood draw
T2Bacteria ≤ 5 min < 5h from blood draw
*With the exception of MR technology, all other TATs refer to time after culture bottle is flagged as positive
MR: magnetic resonance; MALDI TOF: Matrix-assisted laser desorption ionization – time of flight; PNA FISH: Peptide nucleic
acid fluorescence in situ hybridization; PCR: polymerase chain reaction; mPCR: multiplex PCR
33
Implementing RDT
• Involve other departments • Space considerations
• Microbiology • Staff considerations
• Nursing • Microbiology staff
• Pharmacy • Staff receiving alerts
• Antimicrobial stewardship
• Timing
• Infection control
• Batching vs. real-time
• C-suite
• Informational technology • Cost considerations
• Organisms of concern • Technology purchasing vs.
leasing
• Sample considerations • Reagent/cartridge cost
• Blood vs. other
RDT: rapid diagnostic technology
Post-Implementation
• Demonstrate benefit for ongoing utilization
• Time to effective/optimal therapy
• Time to discontinuation/de-escalation
• Time to ID consult
• 30-day readmission
• Length of stay
• Hospital cost of infection
• Hospital cost
• Mortality
Slide courtesy of Karri Bauer, PharmD
34
Additional Readings
• Roadmap to implementing RDT:
• Wenzler E. Implementation and optimization of
molecular rapid diagnostic tests for bloodstream
infections. Am J Health-Syst Pharm 2018;75:1191-202
• Review of other types of RDT (respiratory, CNS,

gastrointestinal)
• Beganovic M. Interplay between rapid diagnostic tests
and antimicrobial stewardship programs among
patients with bloodstream and other severe infections. J
Applied Lab Med 2019; DOI: 10.1373/jalm.2018.026450
Summary
• RDT can be a powerful stewardship tool
• Choice of RDT needs to be individualized to
institution’s needs
• Results must be called in and acted upon by
knowledgeable staff
• If utilizing RDT, consider publishing results!
35

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SIDP – Antimicrobial Stewardship Certificate Program

Antimicrobial Stewardship & Microbiology: Focus on Rapid Diagnostic Tests

Antimicrobial Stewardship & Microbiology:

Monica V. Mahoney, PharmD, BCPS AQ-ID, BCIDP

Selecting Antimicrobial Therapy

Targeted antimicrobial therapy

Antimicrobial susceptibilities available

Empiric Rx Broad Rx Directed Rx

Sepsis, Antibiotics, & Mortality – Oh My!

Kumar et al. Crit Care Med 2006;34:1589-96

Patient Case: Cultures Day 1

Started on: piperacillin/tazobactam & vancomycin

Patient Case: Cultures Day 2

Patient Case: Cultures Day 4

Changed to: ampicillin & ceftriaxone

Selecting Antimicrobial Therapy

Targeted antimicrobial therapy

Antimicrobial susceptibilities available

Rapid Diagnostic Technologies

• Test for bacterial components

Antimicrobial susceptibilities available

IDSA Stewardship Guidelines

Barlam TF et al. Clin Infect Dis 2016;62:e51-e77

Foster RA. Infect Control Hosp Epi 2017

Recipients of RDT Results

ASP: antimicrobial stewardship program; R/F: resident/fellow

Foster RA. Infect Control Hosp Epi 2017

∴ RDT education should be wide-spread

Foster RA. Infect Control Hosp Epi 2017

Antimicrobial susceptibilities available

Gram Negative Organisms

Gram Negative Organisms

Susceptible Moderate Resistant

Antimicrobial susceptibilities available

• Analyze thousands of samples

Slide courtesy of BioMériux

MALDI TOF MS Output

Adapted slide courtesy of BioMériux

MALDI-TOF MS in Real Life

Huang AM. Clin Infect Dis 2013;57:1237-45

Slide courtesy of Brandon Dionne, PharmD

Antimicrobial susceptibilities available

PNA FISH (aka traffic light)

Staphylococcus Gram negative rods

PNA FISH in Real Life

Forrest GN. J Antimicrob Chemother 2006;58:154-8

Slide courtesy of Brandon Dionne, PharmD

Photo courtesy of Katie Lusardi, PharmD

Automated FISH/Imaging in Real Life

RDT: rapid diagnostic technology; LOS: length of stay

MIC: minimum inhibitory concentration

Slide courtesy of Brandon Dionne, PharmD

Antimicrobial susceptibilities available

PCR & mPCR

PCR & mPCR

Detection of S. aureus Detection of MRSA

Buchan BW. J Clin Microbiol 2015;53:804-9

PCR in Real Life

Bauer KA. Clin Infect Dis 2010;51:1074-80

Multiplex Resistance Gene Comparison

Multiplex for Gram Positives

Multiplex for Gram Negatives