Transcript Rapid Diagnostic Testing (RDT) and Antimicrobial Stewardship

Rapid Diagnostic Testing (RDT) and
Antimicrobial Stewardship
South Peninsula Hospital
Goals of Rapid Diagnostic Testing (RDT)
• Decreases time to identification of pathogen from days to hours
• Can distinguish between viral vs bacterial infections
• Allows streamlining to appropriate therapy
• Facilitate the decision about whether or not to prescribe abx
• Prevent the use of unnecessary antibiotics
• Facilitates de-escalation
• Decreased antimicrobial resistance
• Many studies have shown decreased
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Duration of illness
Length of stays
Costs
30-day all cause mortality
Impacts of rapid diagnostic testing in optimizing
antimicrobial selection
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Source: adapted from Goff, DA et al. (2012) Using rapid diagnostic tests to optimize antimicrobial selection in antimicrobial
stewardship programs. Pharmacother 32(8): 677-687.
Rapid Diagnostic tests
Gram-positives, Gram-Negatives, Yeast
• PCR (polymerase chain reaction)
• GeneXpert (Cepheid); FilmArray (Biofire) & others
• Turnaround time @60min
• PNA FISH (peptide nucleic acid fluorescence in situ hybridization)
• GNR Traffic Light PNA FISH (AdvanDx), Yeast Traffic Light PNA FISH
(AdvanDx)
• Turnaround time @90min
• Nucleic Acid
• Verigene (Nanosphere)
• Turnaround time @120 – 150min
• MALDI-TOF matrix-assisted laser desorption ionization-time of flight
• MALTI Biotyper (Bruker Daltonics); VITEK MS (bioMerlieux)
• Turnaround time 10-30min; very expensive; no resistance markers
BioFire Diagnostics
Over 20 Years of Innovations
2000
Applied PCR
• BioThreat Testing
• Food Testing
1990
Idaho Technology, Inc.
1996
Molecular Biology Tools
• LightCycler®
FilmArrayTM
2011: Respiratory Panel
2013: Blood Culture
Identification Panel
2014: Gastrointestinal Panel
FilmArray:
The Fastest Way to Better Results
Easy
• 2 minutes of
hands-on time
Fast
• Run time of about
1 hour
Comprehensive
• Tests for a variety of
pathogens that
cause respiratory,
blood, and
gastrointestinal
infections, as well
antimicrobial
resistance genes
FilmArray:
The Fastest Way to Better Results
– Comprehensive – Panels cover a wide range of targets involved in
causing respiratory, bloodstream, and gastrointestinal infections
Respiratory
Panel
Blood Culture
Identification
Panel
Gastrointestinal
Panel
20
27
22
targets
• 3 bacteria
• 17 viruses
targets
targets
• 19 bacteria
• 5 yeast
• 3 antibiotic resistance
genes
• 13 bacteria
• 5 viruses
• 4 parasites
Respiratory Panel (RP)
Viruses
Adenovirus
Coronavirus HKU1
Coronavirus NL63
Coronavirus 229E
Coronavirus OC43
Human Metapneumovirus
Human Rhinovirus/Enterovirus
Influenza A
Influenza A/H1
Influenza A/H3
Influenza A/H1-2009
Influenza B
FDA-cleared for the first time.
Parainfluenza 1
Parainfluenza 2
Parainfluenza 3
Parainfluenza 4
Respiratory Syncytial Virus
Bacteria
Bordetella pertussis
Chlamydophila pneumoniae
Mycoplasma pneumoniae
Blood Culture Identification (BCID) Panel
Gram+ Bacteria
Gram- Bacteria
Yeast
Enterococcus
Listeria monocytogenes
Staphylococcus
S. aureus
Streptococcus
S. agalactiae
S. pyogenes
S. pneumoniae
Acinetobacter baumannii
Haemophilus influenzae
Neisseria meningitidis
Pseudomonas aeruginosa
Enterobacteriaceae
Enterobacter
cloacae complex
Escherichia coli
Klebsiella oxytoca
Klebsiella pneumoniae
Proteus
Serratia marcescens
Candida albicans
Candida glabrata
Candida krusei
Candida parapsilosis
Candida tropicalis
Antibiotic Resistance
mecA – methicillin resistant
van A/B – vancomycin resistant
KPC – carbapenem resistant
FDA-cleared for the first time.
The FilmArray BCID Panel
Provides Faster Results
 For use on blood culture bottles that are:
– Flagged as positive by a continuously monitoring blood culture instrument
– Positive by Gram stain examination
The FilmArray
– 100 μL sample required
Pathogen ID
Blood
Draw
Blood
Culture
Positive
Gram
Stain
Approximately 1 h
Standard
Testing
12–72 h
5 min
Pathogen ID
Antimicrobial
Susceptibility
Testing
24–72 h
• In a clinical study, organisms covered by the BCID panel were detected 60% faster than
organisms not included in the BCID panel (21.67 vs 53.92 hours, respectively)1
BCID=blood culture identification; ID=identification.
1. Altun O et al. J Clin Microbiol. 2013;51:4130-4136.
Gastrointestinal (GI) Panel
Bacteria
Parasites
Campylobacter (jejuni, coli, and upsaliensis)
Clostridium difficile (Toxin A/B)
Plesiomonas shigelloides
Salmonella
Vibrio (parahaemolyticus, vulnificus, and cholerae)
Vibrio cholerae
Yersinia enterocolitica
Cryptosporidium
Cyclospora cayetanensis
Entamoeba histolytica
Giardia lamblia
Diarrheagenic E. coli/Shigella
Enteroaggregative E. coli (EAEC)
Enteropathogenic E. coli (EPEC)
Enterotoxigenic E. coli (ETEC)
Shiga-like toxin-producing E. coli (STEC)
E. coli O157
Shigella/Enteroinvasive E. coli (EIEC)
FDA-cleared for the first time.
Viruses
Adenovirus F 40/41
Astrovirus
Norovirus GI/GII
Rotavirus A
Sapovirus (I, II, IV, and V)
The FilmArray Panels
The Future of FilmArray
Meningitis
Panel
GI Panel
BCID Panel
Respiratory
Panel
FDA-Cleared
May 2014
Lower
Respiratory
Panel
In development
FDA Clearance
Anticipated
2015
FDA-Cleared
June 2013
FDA-Cleared
May 2011
The FilmArray Platform
Panels
BCID=blood culture identification; GI=gastrointestinal.
Meningitis/Encephalitis Panel:
In Development
Bacteria
Viruses
Escherichia coli K1
Haemophilus influenzae
Listeria monocytogenes
Neisseria meningitidis
Streptococcus agalactiae
Streptococcus pneumoniae
Cytomegalovirus (CMV)
Enterovirus
Epstein-Barr virus (EBV)
Herpes simplex virus 1 (HSV-1)
Herpes simplex virus 2 (HSV-2)
Human herpesvirus 6 (HHV-6)
Human parechovirus
Varicella zoster virus (VZV)
Yeast
Cryptococcus gattii
Cryptococcus neoformans
Taking Out the Guesswork:
Easy-to-Interpret Results
• The FilmArray software processes the data and creates a positive or
negative call for each organism, providing the results in a simple and
easy-to-read report
Clinical Benefits:
Respiratory Panel (RP)
Clinical and Economic Consequences of
Respiratory Infections In the United States
25,000,000
1,026,476
$40 billion
family physician
consultations1
hospitalizations
due to upper
respiratory tract
infections between
1998 and 20062
estimated
annual cost of
non-influenza–
related viral
respiratory tract
infections3
1. Heikkinen T, Järvinen A. Lancet. 2003;361:51-59.
2. Christensen KLY et al. Clin Infect Dis. 2009;49:1025-1035.
3. Fendrick AM et al. Arch Intern Med. 2003;163:487-494.
Unmet Needs in Diagnosing
and Treating Respiratory Infections
Of influenza-positive
children
43% were hospitalized within
two days of symptom onset
Of outpatients with
confirmed RSV infection
RSV=respiratory syncytial virus.
1. Poehling KA et al. Pediatrics. 2013;131(2):206-216.
2. Hall CB et al, N Engl J Med. 2009;360(6):588-598.
3%
1.5%
but only
received antiviral
treatment1
received a specific
diagnosis of RSV
infection2
A Fast and Accurate Diagnosis Can
Ensure Appropriate Treatment
Uncertain diagnosis is one of the primary reasons that
physicians do not prescribe antivirals1
Timeliness
Influenza treatment should be
initiated within 48 hours after
symptom onset2
Timely treatment is associated with
shorter hospitalizations among
critically ill children, faster resolution of
illness, less parental work
absenteeism, reduced risk of
developing otitis media1
1. Poehling KA et al. Pediatrics. 2013;131(2):206-216.
2. Harper SA et al. Clin Infect Dis. 2009;48(8):1003-1032.
Accuracy
The choice of influenza antiviral may
depend on the viral subtype2
Accurate diagnosis of the influenza
subtype can inform treatment
decisions2
A Fast and Accurate Diagnosis Can
Improve Care for Elderly Patients
Respiratory infections, such as RSV, HMPV, and influenza are difficult to
differentiate in older adults due to similar clinical presentations and
seasonal patterns1
Timeliness
Accuracy
Timely antiviral treatment can
improve patient outcomes and reduce
mortality
Early use of antivirals is associated
with rapid viral clearance, fewer
symptoms, reduced progression to
pneumonia, and reduced mortality2
Sensitivity of rapid tests and viral
culture is lower among older patients1
Accurate diagnostic tests are required to
verify illnesses that cannot be confirmed
by symptoms or current tests
HMPV=human metapneumovirus; RSV=respiratory syncytial virus.
1. Widmer K et al. J Infect Dis. 2012;206:56-62.
2. Ison MG. Antiviral Ther. 2007;12(4 Pt B):627-638.
Clinical Benefits of Rapid and Accurate
Diagnosis
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The FilmArray RP provides rapid and accurate results with a turnaround time
of ~1 hour
– FDA cleared for use with nasopharyngeal swab samples (300 μL volume
required)
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Rapid identification of the causative agent of respiratory infections can
improve patient management by:
 Informing timely and
effective antibiotic or
antiviral therapy
 Preventing secondary spread
of infection
 Shortening hospital stays
RP=respiratory panel.
Loeffelholz MJ et al. J Clin Microbiol. 2011;49(12):4083-4088.
 Reducing costs of
unnecessary tests
A Fast and Accurate Diagnosis Can
Reduce Misuse of Antibiotics
An accurate diagnosis reduces overprescribing of
antibiotics and prevents antibiotic resistance1
– Each year, over 10,000,000 courses of antibiotics are prescribed for viral
conditions2
– An estimated 55% of antibiotic prescriptions for ARTIs are unnecessary3
Antibiotic Prescriptions for Adults With Nonpneumonic Acute Respiratory Tract Infections, by Diagnosis 3
63% of all patients with an ARTI received an antibiotic,
Narrow-Spectrum Antibiotics
including 29% who received a narrow-spectrum agent and
Broad-Spectrum Antibiotics
34% who received a broad-spectrum agent
ARTI=acute respiratory tract infection; URTI=upper respiratory tract infection.
1. Smolinski M et al. Microbial Threats to Health: Emergence, Detection, and Response. Washington, DC: The National
Academies Press; 2003.
2. Centers for Disease Control and Prevention. www.cdc.gov/getsmart/campaign-materials/about-campaign.html.
Accessed February 21, 2013.
3. Steinman MA et al. JAMA. 2003;289(6):719-725.
FilmArray Can Help Save Money and
Generate Revenue

Implementation of FilmArray RP in a core laboratory to provide service
24 hours a day, 7 days a week for respiratory virus diagnosis
EMERGENCY
ROOM
71%
900 hrs
samples collected from
emergency departments
emergency room
time saved
~$8,723,700–
$11,968,200
additional revenue
RP=respiratory panel.
Xu M et al. Am J Clin Pathol. 2013;139:118-123.
Clinical Benefits:
Blood Culture Identification
(BCID) Panel
Septicemia: Mortality and Costs
• Septicemia remains a leading cause of death in both adults and
infants in the United States, and is the leading cause of death in
noncardiac ICUs1,2
Sepsis2
Mortality2
$24.3 billion2
>1.1 million cases
annually
>40%
annual cost
ICU=intensive care unit.
1. Heron M. Nat Vit Stat Rep. 2012;60:1-95.
2. Moore LJ, Moore FA. Surg Clin North Am. 2012;92(6):1425-1443.
Challenges in Diagnosing Sepsis
Early signs of sepsis are nonspecific and often missed, resulting in delays
in treatment.1
In a survey of 917 physicians, only 27% were able to correctly recognize sepsis.2
Correct answers
for each diagnosis (%)
100
80
60
40
20
0
SIRS
Infection
Sepsis
Severe sepsis
Septic shock
SIRS=systemic inflammatory response syndrome.
1. Moore LJ et al. Surg Clin N Am. 2012;92(6):1425-1443.
2. Assunção M et al. J Crit Care. 2010;25(4):545-552.
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Unmet Needs in Treating Sepsis
58%
A retrospective cohort
analysis of 760 patients
with severe sepsis1
In
,
therapy was
delayed
31% received
inappropriate
antibiotic treatment
42%
had
resistance to the
antibiotic
administered
Patients who progress to septic shock have a 7.6% increase in
mortality every
1. Shorr AF et al. Crit Care Med. 2011;39(1):46-51.
2. Kumar A et al. Crit Care Med. 2006;34(6):1589-1596.
hour
while not on appropriate therapy.2
A Fast Diagnosis Can Ensure Timely Treatment,
Which May Reduce Mortality
Mortality Rate of Sepsis, Severe Sepsis, and Septic Shock1
60
50
40
30
Mortality rate (%)
70
61%
42%
26%
20
10
0
Timely treatment is essential to prevent the progression of sepsis to septic
shock and reduce mortality1-3
Infection/sepsis
Severe sepsis
1. Alberti C et al, for the European Sepsis Study Group. Am J Respir Crit Care Med. 2005;171(5):461-468.
2. Shorr AF et al. Crit Care Med. 2011;39(1):46-51.
3. Moore LJ et al. Surg Clin North Am. 2012;92(6):1425-1443.
Septic shock
Mortality Rate in Septic Patients
Mortality Rates for 29,273 Patients by Blood Culture Result and
Type of Bacteremia1
Cumulative mortality (%)
40
Polymicrobial or fungemia
Gram-positive
Gram-negative
Blood culture negative
30
20
10
0
0
30
60
90
Days of admission
120
150
180
Septic patients with polymicrobial infections have the highest mortality.1
Polymicrobial infections have been detected in 41.5% of HA infections,
28.6% of CA infections, and 33.8% of ICU-acquired infections.2
CA=community-acquired; HA=hospital-acquired; ICU=intensive care unit.
1. Sogaard M et al. BMC Infectious Diseases. 2011;11:139.
2. Alberti C et al. Intensive Care Med. 2002;28(2):108-121.
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Clinical Benefits:
The FilmArray Gastrointestinal
(GI) Panel
Gastrointestinal Infections:
Mortality and Costs
 211–375 million episodes of diarrheal illness occur in the United
States annually, resulting in:
73,000,000
physician
consultations
$6 billion
1,800,000
3,100
hospitalizations
deaths
Guerrant RL et al. Clin Infect Dis. 2001;32:331-351.
spent on
medical care and
lost productivity
FilmArray GI Panel:
Potential Patient and Provider Benefits


Rapid diagnosis of the causative agent of GI infections and appropriate treatment
decisions can improve patient outcomes and decrease healthcare costs1,2
The FilmArray GI panel is easy to use, and provides rapid and accurate results in
~1 hour3
Provider
Provides more
comprehensive
testing4
Informs improved
quality of care2
Guides appropriate
follow-up3
1.
2.
3.
4.
Patient
Fast results3
Comprehensive
coverage3
Accurate
pathogen
identification3
Shortened illness1
Shorter hospital visits2
Reduced morbidity1
Prevents secondary
transmission1
Guerrant RL et al. Clin Infect Dis. 2001;32:334-351.
Nanosphere. Enteric Pathogens Test. www.nanosphere.us/products/enteric-pathogens-test. Accessed February 10, 2014.
FilmArray GI [Instruction Booklet]. Salt Lake City, UT: BioFire Diagnostics, LLC.
Buss SN et al. J Clin Microbiol. 2013;51:3909.
RDT Intervention Examples
• GI Panel
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Pt on cipro & metronidazole for diarrhea; Rapid GI panel showed STEC –
shiga like toxin producing E coli
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STEC should not be treated with abx as it can precipitate hemolytic uremic
syndrome
Abx d/c’ed
Several pts being treated with metronidazole for presumed C diff diarrhea;
Rapid GI panel showed campylobacter
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Abx changed to levofloxacin
33yo up here from Seattle visiting parents w diffuse watery diarrhea;
thought she had gotten sick from kombucha tea at our Saturday market;
Rapid GI panel showed vibrio species (not vibreo cholerae)
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Kachemak Bay oysters ???
On interview the pt remembered she had eaten raw oysters in Seattle just prior
to travel
RDT Intervention Examples
• Blood culture
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Vanco started empirically for ?? sepsis; Rapid blood culture does not
detect methicillin resistance
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Vanco d/c’ed;
2014 after implementation of ASP, BUT prior to FilmArray vanco use decreased
by 7%
Vanco use decreased by 20% in 2014 after implementation of FilmArray
IV Rx abuser w hx of endocarditis empirically started on vanco based on
hx
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Rapid blood culture ID’ed MRSA and Candida parapsilosis
Fluconazole started; being able to identify the candida species aides in selection
of antifungal; parapsilosis less susceptible to eichonocandins (micafungin)
RDT Intervention Examples
• Strep rapid screen (illumigene)
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16yo in the ED w severe pharyngitis; WBC 23; pt allergic PCN; MD
thinks Grp A strep, so pt started on CFZ
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Rapid strep negative
Fusobacterium 2x as likely to cause pharyngitis in this age group
Abx changed to clindamycin IV
Intervention took place prior to patient even getting out of the ED to the floor
• C diff rapid screen (GI Panel or illumigene)
• Rapid C diff results used many times to either start treatment or
discontinue empiric tx
RDT Intervention Examples
• Pt on 6wk daptomycin IV daily as OP for hardware infection; g+ cocci;
pt had been on multiple abx
• Propionibacterium acnes finally grew; slow growing g+ anaerobe; most
labs don’t keep plates long enough for it to grow; gaining notoriety for
causing hardware infections
• Pt changed to ceftriaxone 2g IV daily
• Hospital cost savings $21,000 vs $500 over the course of tx
Practical Notes
• Utility & cost-effectiveness is dependent on clinician’s reacting to data
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These tests are of little value if the results are not acted on quickly
Success depends on a close relationship between lab & pharmacy
• All rapid test results, culture data (preliminary & final) printed to
pharmacy printer
• RPh contacts provider with suggestions for appropriate abx
• SPHs antimicrobial stewardship program has been in place since
January, 2014
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Medical staff very receptive to RPh recommendations and now frequently
initiate contact with RPh for suggestions
Practical Notes
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SPH antimicrobial stewardship program started January 2014 with one RPh
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# interventions, abx cost/inpt day, & abx burden all statistically significantly improved
compared to no ASP
2015 a second trained RPh involved; Jan – Jun impact:
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Interventions increased by 72% (p<0.02)
Antibiotic cost savings/inpt day increased by 64% (p<0.02)
Overall antimicrobial burden decreased by 4.2% (p<0.02)
No Clinical Decision Support System (CDSS)
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TheraDoc, Sentri7, MedMined, Vigilanz
Use computer algorithms to target potential antimicrobial interventions
SPH is small so all done manually
Procalcitonin
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Medical staff so receptive to our suggestions we feel our timing is perfect for implementing
procalcitonin testing
Investigating cost
Questions?