THE FAST AND THE SUSCEPTIBLE: RAPID DIAGNOSTICS IN INFECTIOUS - - PowerPoint PPT Presentation
THE FAST AND THE SUSCEPTIBLE: RAPID DIAGNOSTICS IN INFECTIOUS DISEASE Brandon Dionne, PharmD, BCPS, AAHIVP Assistant Clinical Professor Northeastern University Clinical Pharmacy Faculty Infectious Diseases Brigham and Womens Hospital
Brandon Dionne, PharmD, BCPS, AAHIVP Assistant Clinical Professor Northeastern University Clinical Pharmacy Faculty – Infectious Diseases Brigham and Women’s Hospital
Increase in mortality of 7.6% for each hour delay in septic shock
Vancomycin has been shown to be inferior to β-lactam antibiotics for methicillin-susceptible
Staphylococcus aureus (MSSA)
Kumar A, et al. Crit Care Med. 2006;34:1589-1596. Kim SH, et al. Antimicrob. Agents Chemother. 2008;52(1):192-197. Hecker MT, et al. Arch Intern Med 2003;163:972-978.
Physician, pharmacist, epidemiologist, clinical microbiologist, infection preventionist,
information systems specialist
Secondary goal to lower costs
Dellit TH, et al. Barlam TF, et al. 2016;62(10):e51-77 Clin Infect Dis. 2007;44(2):159-177. Clin Infect Dis.
Total # New Antibacterial Agents
Adapted from Septimus EJ, Owens RC. Clin Infect Dis 2011;53:S8-S14.
1 = Methicillin-resistant Staphylococcus aureus (MRSA) 2 = Vancomycin-resistant Enterococci (VRE) 3 = Imipenem-resistant Pseudomonas aeruginosa 4 = Imipenem-resistant Acinetobacter baumanii 5 = Fluconazole-resistant Candida spp.
Differing levels of complexity and turnaround times (TATs)
Some can detect antimicrobial resistance
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Culture Gram stain Colony isolation Biochemical tests Identification and susceptibility
Goff DA, et al. Pharmacotherapy. 2012;32(8):677–687
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Individual tests are inexpensive
http://www.sigmaaldrich.com/technical-documents/articles/biology/custom-dna-oligos-qc-analysis-by-mass-spectrometry.html
46 hour reduction in time to de-escalation (p = 0.004) 36.7 hour improvement in time to effective treatment in patients with inactive therapy (p < 0.001) Reduction in LOS by 2.6 days (p = 0.01) and cost by ~$20,000 (p = 0.009)
Decrease in time to effective antibiotic therapy (20.4 vs 30.1 hours; p = 0.021) 2.8 day decrease in mean LOS (p = 0.07) Reduction in mortality from 20.3% to 14.5% (p = 0.02)
Perez KK, et al. Arch Pathol Lab Med. 2013;137:1247-1254. Huang AM, et al. Clin Infect Dis. 2013;57:1237-1245.
Lysing kits may allow detection directly from
positive blood culture
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Reagents selected based on gram stain Can detect polymicrobial infections
http://www.opgen.com/pathogenid/quickfish-products/
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Decrease in mean time to targeted therapy from 2.3 to 0.6 days (p = 0.0016) Mean time to species identification of 0.2 vs 4.0 days (p < 0.001) Cost savings of about $415 per patient
Decrease in caspofungin DDD from 8.7 to 3.2 in patients with C. albicans (p < 0.05) Decrease in cost of about $1800 per patient
$1700 after accounting for cost of PNA FISH
Heil EL, et al. Am J Health Syst Pharm. 2012;69:1910-1914. Forrest GN, et al. J Clin Microbiol. 2006;44(9):3381-3383.
http://www.advandx.com/wp-content/uploads/2014/07/ADV-224-Revd-QF-Staph-Brochure-v5.pdf
Reduction in mortality (16.8% vs 7.9%, p = 0.05)
Biggest change in ICU mortality (47.8% vs 9.5%, p = 0.01)
2 day decrease in duration of antimicrobial therapy and length of stay (LOS)
Use of PNA FISH led to a significant reduction in LOS of 2 days (p < 0.05) Non-significant difference in defined daily doses Reduction in total cost of care by about $4000 per patient
Ly T, et al. Ther Clin Risk Manag. 2008;4:637-640. Forrest GN, et.al. J Antimicrob Chemother. 2006;58:154-158.
3 day reduction in identification of E. faecalis (1.1 vs 4.1 days; p < 0.001) 2.3 day reduction in identification of E. faecium (1.1 vs 3.4 days; p < 0.001) Decreased time to appropriate therapy from 3.1 to 1.3 days (p < 0.001) 26% vs 45% 30-day mortality (p = 0.04)
Forrest GN, et al. Antimicrob Agents Chemother. 2008;52:3558-3563.
http://www.opgen.com/pathogenid/quickfish-products/gram-negative-quickfish/
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Organism Time (h) T echnology Batch Pure colony Auto- mated CLIA Complexity Trade Name MRSA 2 PCR Yes No Yes High Roche LightCycler MRSA MSSA, MRSA, CoNS 2 Multiplex PCR Yes No Yes High BD GeneOhm Staph SR MSSA, MRSA, CoNS 1 Multiplex PCR No No Yes Moderate Cepheid Xpert MRSA/SA BC MSSA, MRSA 1 Multiplex PCR No No Yes Moderate Cepheid Xpert MRSA/SA SSTI
Adapted from Bauer KA, et al. Clin Infect Dis. 2014;59(S3):S134-5145
55% vs 76% (p < 0.01) of patients without S. aureus bacteremia treated for S. aureus infection 5.2 vs 49.8 hours (p = 0.007) until MRSA treatment switched to MSSA treatment
Mean reduction in time to MSSA treatment of 1.6 d (p = 0.02) Length of stay reduced by 6.2 days (p = 0.07) Hospital costs reduced by $21,387 (p = 0.02)
Parta M, et al. Infect Control Hosp Epidemiol. 2010;31(10):1043-1048. Bauer KA, et al. Clin Infect Dis. 2010;51(9):1074-1080.
Hands-on time of 2 minutes and turnaround time of 1-2 hours Two major mPCR platforms available for positive blood cultures
NanosphereVerigene
BC-GP detects mecA (MRSA) and vanA/B (VRE) BC-GN detects CTX-M (extended spectrum beta-lactamase) and IMP
, KPC, NDM, OXA, and VIM (carbapenemases)
Does not detect yeast
BioFire FilmArray
BCID detects mecA, vanA/B, and KPC Detects Candida albicans, C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis
Pathogen FilmArray Verigene Enterococcus ✔ ✔
✔
✔ Staphylococcus ✔ ✔
✔ ✔
✔
✔ Streptococcus ✔ ✔
✔
✔ ✔
✔ ✔
✔ ✔ Listeria ✔ (L. monocytogenes) ✔
Pathogen FilmArray Verigene Acinetobacter ✔ (A. baumanii) ✔ Pseudomonas aeruginosa ✔ ✔ Neisseria meningitidis ✔ Haemophilus influenzae ✔ Enterobacteriaceae ✔ Citrobacter ✔ Enterobacter ✔ (E. cloacae complex) ✔ Escherichia coli ✔ ✔ Klebsiella oxytoca ✔ ✔ Klebsiella pneumoniae ✔ ✔ Proteus ✔ ✔ Serratia marcescens ✔ Not FDA-cleared
Pathogen identification 10.9 h vs 37.9 h (p < 0.001) Reductions in LOS, 30-day mortality, and mortality associated with multidrug-resistant organisms Reduction in time to effective therapy for ESBL-producing organisms
Time to optimal therapy of 26.7 vs 60.2 hours (p = 0.001) Time to effective antibiotics reduced from 6.9 to 3.4 hours (p = 0.03) Unnecessary antibiotics for contaminants decreased from 76% to 26% (p < 0.001)
Walker T, et al. J Clin Microbiol. 2016;54(7):1789-96. Messacar K, et al. J Pediatric Infect Dis Soc. 2017;6(3):267-274.
Verigene BC-GP – 100% agreement FilmArray BCID – 85% agreement
Missed 2 CoNS and 1
Viridans group Streptococcus
Identified 1 MSSA as MRSA and 8 CoNS as CoNS+Enterococcus
Sailey CJ, et al. Abstract #D-106 at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, District of Columbia, United States; September 2014.
Other RDTs may require multiple panels/reagents for each of these types of organisms
Case report of a patient found to have GPCCs on gram stain
FilmArray uncovered a polymicrobial infection, including gram positive, gram negative, and fungal pathogens Verigene BC-GN likely would not have been run based on gram stain
Timbrook T, et al. J Clin Microbiol. In Press.
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Accelerate Pheno
PhenoT
est BC
Combination of automated FISH and “morphocellular kinetic analysis”
Uses fluorescence imaging and growth curve algorithm to predict susceptibility
Hands-on time of 2 minutes Turnaround time of 1.33 hours to identification and 6.6 hours to susceptibility 97.4% sensitivity and 99.3% specificity for pathogen identification 95.1% essential agreement and 96.0% categorical agreement for susceptibility
Willey BM, et al. Open Forum Infect Dis. 2017; 4(Suppl 1): S594–S595. http://acceleratediagnostics.com/news/accelerate-diagnostics-submits-de-novo-request-fda-accelerate-pheno-system-accelerate-phenotest-bc-kit/
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T2Dx
T2Candida panel available T2Bacteria (currently research use only in US)
Superparamagnetic particles bind pathogen changes in magnetic resonance signal Hands-on time of 2 minutes Identifies C. albicans, C. tropicalis, C. parapsilosis, C. krusei and C. glabrata direct from whole
99.4% specificity and 91% sensitivity in contrived trial (250 seeded and 50 negative controls)
Mylonakis E, et al. Clin Infect Dis. 2015;60(6):892-9.
Average time to identification by
conventional methods was 2.2 ± 1.3 days vs
Average time to start antifungal therapy was
3.5 days for conventional vs 0.6 days for T2Candida in simulation
Negative T2Candida could also be used for
discontinuation
Aitken SL, et al. Ann Pharmacother. 2014;48(6):683-690.
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Carver PL, et al. J Clin Microbiol. 2008;46:2381-2383.
Phase I –Without pharmacist intervention Phase II – With pharmacist intervention
Banerjee R, et al. Clin Infect Dis. 2015;61(7):1071-80.
Timbrook TT, et al. Clin Infect Dis. 2017;64(1):15-23.
May need to work with lab to justify costs through other savings to health system
RDT Specimen Resistance/ Susceptibility Cost Hardware/T est Hands-on Time (mins) TAT (hrs) MALDI-TOF Pure colony
2 0.1 PNA FISH Positive BCx
5+ 0.33 mPCR Positive BCx + $$/$$ 2 1-2 FISH/Imaging Positive BCx ++ $$/$$ (?) 2 1.5/6.5 Magnetic Resonance *Direct from whole blood
2 <6*
Often no difference is seen without active notification and follow-up
Potential for use in targeted therapy for multidrug-resistant organisms