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1
The Effect of Molecular Rapid Diagnostic Testing on Clinical Outcomes in Bloodstream
Infections: A Systematic Review & Meta-analysis
Tristan T. Timbrook
1,2
, Jacob B. Morton
1,2
, Kevin W. McConeghy
3
, Aisling R. Caffrey
1,2,3
,
Eleftherios Mylonakis
4
, Kerry L. LaPlante
1,2,3
1. Rhode Island Infectious Diseases Research Program, Providence Veterans Affairs Medical
Center, Providence, RI, USA
2. College of Pharmacy, University of Rhode Island, Kingston, RI, USA
3. Center of Innovation in Long Term Services and Supports, Providence Veterans Affairs
Medical Center, Providence, RI, USA
4. Infectious Diseases Division, Warren Alpert Medical School of Brown University,
Providence, RI, USA
Corresponding Author: Kerry L. LaPlante, Pharm.D., FCCP, Professor, University of Rhode
Island College of Pharmacy, 7 Greenhouse Rd, Suite 295A, Kingston, RI 02881, (401) 874-
5560 (office); KerryLaPlante@uri.edu
Alternative Corresponding Author: Aisling R. Caffrey, PhD, MS, Assistant Professor, University
of Rhode Island College of Pharmacy, 7 Greenhouse Rd, Suite 265B, Kingston, RI 02881, (401)
874-5320 (office); Aisling_Caffrey@uri.edu
Summary: Molecular rapid diagnostic testing (mRDT) in bloodstream infections significantly
decreased the risk of mortality overall and with stewardship but not without. Time to effective
therapy, as well as length of stay, were decreased with mRDT.
2
Background: Previous reports on molecular rapid diagnostic testing (mRDT) do not
consistently demonstrate improved clinical outcomes in bloodstream infections (BSIs). This
meta-analysis seeks to evaluate the impact of mRDT in improving clinical outcomes in BSIs.
Methods: We searched PubMed, CINAHL, Web of science, and EMBASE through May 2016
for BSI studies comparing clinical outcomes by mRDT and conventional microbiology methods.
Results: Thirty-one studies were included with 5,920 patients. Risk of morality was significantly
lower with mRDT as compared to conventional microbiology methods (OR 0.66, 95% CI 0.54-
0.80) yielding a NNT of 20. The risk of mortality was slightly lower with mRDT in studies with
antimicrobial stewardship programs (ASPs) (OR 0.64, 95% CI 0.51-0.79) and non-ASP studies
failed to demonstrate a significant decrease in risk of mortality (OR 0.72, 95% CI 0.46-1.12).
Significant decreases in mortality risk were observed with both Gram-positive (OR 0.73, 95% CI
0.55-0.97) and Gram-negative organisms (OR 0.51, 95% CI 0.33-0.78) but not yeast (OR 0.90,
95% CI 0.49-1.67). Time to effective therapy decreased by a weighted mean difference of -5.03
hours (95% CI -8.60 to -1.45) and length of stay decreased by -2.48 days (95% CI -3.90 to -
1.06).
Conclusions: For BSIs, mRDT was associated with significant decreases in risk of mortality in
the presence of a ASP, but not in its absence. Additionally, mRDT decreased time to effective
therapy and length of stay. mRDT should be considered as part of the standard of care in
patients with BSIs.
3
Background
Bloodstream infections (BSIs) are associated with significant morbidity, mortality, and increased
length of stay (LOS) [1,2]. Delayed administration of effective antibiotics increases the risk of
mortality and therefore correct selection of an antibiotic regimen early in the treatment process
is paramount [3,4]. Delayed identification of the causative organism and culture susceptibilities
may often be responsible for delays in optimal antimicrobial therapy. Molecular rapid diagnostic
testing (mRDT), which includes tests such as polymerase chain reaction (PCR), matrix-assisted
laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), and peptide
nucleic acid fluorescent in situ hybridization (PNA-FISH), has improved upon conventional
microbiological methods, reducing time to organism identification, optimizing antimicrobial
therapy, and subsequently improving clinical outcomes, including mortality [5].
Advancement of RDT is now one of five overarching goals from the National Action Plan for
Combating Antibiotic-Resistant Bacteria [6]. Additionally, the 2016 Infectious Diseases Society
of America (IDSA) antimicrobial stewardship program (ASP) guidelines recommend the use of
rapid diagnostic testing with ASP support and intervention as an addition to conventional
methods for blood specimens to improve clinical outcomes [7]. Widespread implementation of
this technology has been limited due to inadequate outcomes data and high costs [8]. A recent
meta-analysis included evaluations of the clinical benefits of molecular and phenotypic rapid
diagnostics in BSIs, but was limited by the time frame of the literature included, with the most
recent study being published in 2012 [9]. Additionally, the impact on LOS was not assessed,
nor was the effect on mortality according to ASP presence. The objective of this systematic
review and meta-analysis was to provide a comprehensive and up-to-date assessment of
mRDT on mortality, time to effective therapy, and LOS, when compared to conventional
microbiology methods in patients with BSIs.