Impact of a Rapid Microarray-Based Assay for Identification of Positive Blood Cultures for Treatment Optimization for Patients with Streptococcal and Enterococcal Bacteremia

Abstract

Implementation of the Verigene Gram-positive blood culture test led to reductions in time to acceptable antibiotic overall (1.9 versus 13.2 h, respectively; P ‫؍‬ 0.04) and time to appropriate antibiotic for patients with vancomycin-resistant Enterococcus (4.2 versus 43.7 h; P ‫؍‬ 0.006) and viridans group Streptococcus (0.2 versus 7.1 h; P ‫؍‬ 0.02). Enterococci and streptococci are frequent causes of bloodstream infections (BSIs), which are associated with high mortality when inappropriately treated (1). Timely initiation of appropriate antibiotics is vital, as this permits effective targeting of causative pathogens, decreased antimicrobial exposure, and possible cost savings. Therefore, rapid molecular tests are being used with increasing frequency to facilitate antimicrobial stewardship efforts. The FDA-cleared Verigene Gram-positive blood culture test (BC-GP) (Nanosphere, Inc., Northbrook, IL) detects bacterial DNA from blood cultures positive for Staphylococcus, Streptococcus, Enterococcus, and Listeria spp. It also identifies mecA, which confers methicillin resistance in staphylococci, and vanA and vanB genes, which confer vancomycin resistance in enterococci.We previously published a targeted treatment algorithm based on BC-GP results (2). In this study, we evaluated clinical outcomes associated with implementation of the BC-GP technology and targeted treatment algorithm in patients with streptococcal and enterococcal bacteremia in comparison with traditional microbiological methods. The primary outcome was time to appropriate antibiotic. Secondary outcomes included time to acceptable antibiotic, time to culture clearance, length of stay (LOS), and mortality.This study, approved by the University of North Carolina Institutional Review Board, used a quasiexperimental design comparing pre-and postintervention groups over 17 months. Patients with blood cultures positive for Gram-positive cocci (GPC) in pairs and/or chains were included. Subjects were excluded if they had polymicrobial blood cultures, had positive cultures for Streptococcus or Enterococcus spp. in both the case and control periods, or were still hospitalized or if the positive blood culture was classified as a contaminant (i.e., one bottle positive for viridans group streptococci [VGS]). Additionally, if a subject had a second blood culture that was positive for the same organism within 14 days of the first culture, the second culture was excluded.In the preintervention period, Gram stain results were documented in the electronic medical record (EMR) system and phoned to the patient's primary team. After BC-GP implementation, Gram stain results were still phoned to the primary team; however, if the stain was positive for GPC in pairs and/or chains, the BC-GP test was performed. The result was communicated by microbiology laboratory staff to the pharmacist on call, who referred to a treatment algorithm based on local susceptibility patterns and clinical guidelines to recommend targeted therapy (2). BC-GP results were confirmed by conventional...

Clinical Performance of the Novel GenMark Dx ePlex Blood Culture ID Gram-Positive Panel

“…Resistance gene detection and/or rapid phenotypic testing is important for early optimization of treatment. Several studies have demonstrated that when either of these is combined with stewardship interventions, the median time to optimal therapy, especially for methicillin-susceptible S. aureus (MSSA) and Enterococcus species, can be shortened by 14 h to more than 24 h (11,13,44,45). In this study, vanA prevalence was low (n ϭ 8 vanA enterococci) among the prospective samples, and no vanB-containing enterococci were detected.…”

Prospective intervention study with a microarray-based, multiplexed, automated molecular diagnosis instrument (Verigene system) for the rapid diagnosis of bloodstream infections, and its impact on the clinical outcomes

“…Due to the their rapidity and high performance for bacterial identification and the prediction of antimicrobial resistance, the potential for significant benefits has been anticipated by increasing the rate of early administration of effective antimicrobial agents and reducing the rate of administration of unnecessary antimicrobial agents [11,15,19]. However, these potential benefits have not yet been widely proven in clinical trials, and were only partially performed for Streptococcus and Enterococcus species [28,29].…”

Experience With Rapid Microarray-Based Diagnostic Technology and Antimicrobial Stewardship for Patients With Gram-Positive Bacteremia

“…2 An emerging development and increasingly popular ASP action is to collaboratively develop real-time interventions with rapid diagnostic technology: peptide nucleic acid fluorescent in situ hybridization (PNA-FISH), 3 polymerase chain reaction tests, 4,5 matrix-assisted laser desorptionionization/time-of-flight mass spectrometry (MALDI-TOF MS), 6 and microarray tests. [7][8][9] As new diagnostic tests become available, the Infectious Diseases Society of America recommends outcomes research to document the effect of these tests on patient care. 10 The Verigene Gram-positive blood culture (BC-GP) test (Nanosphere, Northbrook, IL) utilizes microarray technology to detect specific bacterial DNA from positive blood cultures.…”

“…Prior reports have demonstrated use of rapid microarray technology, and ASPs have been shown to reduce the time to appropriate antimicrobial use and hospital length of stay (LOS). [7][8][9] Most reports are limited to a single genus or species, do not include an active stewardship component, or have small sample sizes. In this study, we evaluated the impact of the rapid microarray technology and ASP intervention on clinical outcomes.…”