Randomized trial of rapid multiplex polymerase chain reaction–based blood culture identification and susceptibility testing
Open accessAbstract
BACKGROUND: The value of rapid, panel-based molecular diagnostics for positive blood culture bottles (BCBs) has not been rigorously assessed. We performed a prospective randomized controlled trial evaluating outcomes associated with rapid multiplex PCR (rmPCR) detection of bacteria, fungi, and resistance genes directly from positive BCBs. METHODS: A total of 617 patients with positive BCBs underwent stratified randomization into 3 arms: standard BCB processing (control, n = 207), rmPCR reported with templated comments (rmPCR, n = 198), or rmPCR reported with templated comments and real-time audit and feedback of antimicrobial orders by an antimicrobial stewardship team (rmPCR/AS, n = 212). The primary outcome was antimicrobial therapy duration. Secondary outcomes were time to antimicrobial de-escalation or escalation, length of stay (LOS), mortality, and cost. RESULTS: Time from BCB Gram stain to microorganism identification was shorter in the intervention group (1.3 hours) vs control (22.3 hours) (P < .001). Compared to the control group, both intervention groups had decreased broad-spectrum piperacillin-tazobactam (control 56 hours, rmPCR 44 hours, rmPCR/AS 45 hours; P = .01) and increased narrow-spectrum β-lactam (control 42 hours, rmPCR 71 hours, rmPCR/AS 85 hours; P = .04) use, and less treatment of contaminants (control 25%, rmPCR 11%, rmPCR/AS 8%; P = .015). Time from Gram stain to appropriate antimicrobial de-escalation or escalation was shortest in the rmPCR/AS group (de-escalation: rmPCR/AS 21 hours, control 34 hours, rmPCR 38 hours, P < .001; escalation: rmPCR/AS 5 hours, control 24 hours, rmPCR 6 hours, P = .04). Groups did not differ in mortality, LOS, or cost. CONCLUSIONS: rmPCR reported with templated comments reduced treatment of contaminants and use of broad-spectrum antimicrobials. Addition of antimicrobial stewardship enhanced antimicrobial de-escalation. CLINICAL TRIALS REGISTRATION: NCT01898208.
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Antimicrobial stewardship programs are optimally positioned to improve response and outcomes associated with RDTs.
“Antimicrobial stewardship programs (ASP) are optimally positioned to improve response and outcomes associated with RDTs.”
From Analysis of the Clinical Impact of the BioFire FilmArray Meningitis Encephalitis Panel on Antimicrobial Use and Duration of Therapy at an Academic Medical Center (2022) · cites this paper as [21]
The Discussion reports that adding antimicrobial stewardship to rapid PCR results produced more frequent and timelier antibiotic de-escalation, supporting improved clinician response. It also says the trial found no differences in clinical or cost outcomes between arms, so the broader claim of improved outcomes is not established by this study. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe best evidence for impact of ASP with RDTs is with multiplex PCR-based blood culture identification (BCID) panels.
“The best evidence for impact of ASP with RDTs is with multiplex PCR-based blood culture identification (BCID) panels [20,21].”
Rapid ID and AST result availability contributes to faster therapy modification.
“It is known that rapid ID and AST result availability contributes to faster therapy modification [16–18].”
From Lab efficiency and improvements in the management of bloodstream infections: a before and after study (2025) · cites this paper as [17]
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- Authors
- Banerjee, R., Teng, C. B., Cunningham, S. A., Ihde, S. M., Steckelberg, J. M., Moriarty, J. P., Shah, N. D., Mandrekar, J. N., & Patel, R.
- Affiliations
- Mayo Clinic (US)
- National University of Singapore (SG)
- Corresponding author
- Banerjee, Ritu
- ORCID
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-07-20
- Volume
- 61
- Issue
- 7
- Pages
- 1071-1080
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- PMC
- PMC4560903
- OpenAlex
- W2159643438
- Cited by
- 570
- References
- 27
- Citations by year
- 2026: 60 · 2025: 55 · 2024: 47 · 2023: 66 · 2022: 46 · 2021: 52 · 2020: 56 · 2019: 50 · 2018: 46 · 2017: 45 · 2016: 37 · 2015: 10
- FWCI
- 37.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Infectious Diseases (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health (NIH)
- the National Institute of Allergy and Infectious Diseases of the NIH (UM1AI104681))
- the National Center for Advancing Translational Sciences (KL2 TR000136))
- BioFire Diagnostics (bioMérieux, Salt Lake City, Utah).
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Antibiotic Use and Resistance
- Health Sciences › Medicine › Oncology › Neutropenia and Cancer Infections
- Keywords
- blood culture identification, antimicrobial susceptibility testing, antimicrobial stewardship, antibiotic de-escalation, broad-spectrum antibiotic use, piperacillin-tazobactam, beta-lactam antibiotics, molecular diagnosis, length of hospital stay, mortality, health care costs
- MeSH terms
- Adult, Aged, Aged, 80 and over, Anti-Bacterial Agents, Bacteria, Female, Humans, Male, Microbial Sensitivity Tests, Middle Aged, Prospective Studies, Bacteremia, Drug Resistance, Bacterial, Molecular Typing, Multiplex Polymerase Chain Reaction
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