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

Abstract

The Verigene Gram-positive blood culture test (BC-GP) and the Verigene Gram-negative blood culture test (BC-GN) identify representative Gram-positive bacteria, Gram-negative bacteria and their antimicrobial resistance by detecting resistance genes within 3 h. Significant benefits are anticipated due to their rapidity and accuracy, however, their clinical utility is unproven in clinical studies. We performed a clinical trial between July 2014 and December 2014 for hospitalized bacteremia patients. During the intervention period (N = 88), Verigene BC-GP and BC-GN was used along with conventional microbiological diagnostic methods, while comparing the clinical data and outcomes with those during the control period (N = 147) (UMIN registration ID: UMIN000014399). The median duration between the initiation of blood culture incubation and the reporting time of the Verigene system results was 21.7 h (IQR 18.2-26.8) and the results were found in 88% of the cases by the next day after blood cultures were obtained without discordance. The hospital-onset infection rate was higher in the control period (24% vs. 44%, p = 0.002), however, no differences were seen in co-morbidities and severity between the control and intervention periods. During the intervention period, the time of appropriate antimicrobial agents' initiation was significantly earlier than that in the control period (p = 0.001) and most cases (90%; 79/88) were treated with antimicrobial agents with in-vitro susceptibility for causative bacteria the day after the blood culture was obtained. The costs for antimicrobial agents were lower in the intervention period (3618 yen vs. 8505 yen, p = 0.001). The 30-day mortality was lower in the intervention period (3% vs. 13%, p = 0.019).

Clinical Impact of Laboratory Implementation of Verigene BC-GN Microarray-Based Assay for Detection of Gram-Negative Bacteria in Positive Blood Cultures

“…At our institution, the cost savings from BC-GN implementation would amount to ϳ$11,661 per Gram-negative bacteremia case with ICU admission. Although length of ICU stay has not been frequently examined in studies specific to the BC-GN microarray panel, our findings are similar to those from one study that included the BC-GN and BC-GP panels and to another study on antibiotic-resistant Gram-negative bacteria rapidly identified by mass spectrometry and direct from blood culture broth susceptibility (21,26). Conversely, we did not find significant change in the time to de-escalation of broad-spectrum antibiotics or in length of hospital stay.…”

“…This finding has been reported by others who used the Verigene system but combined data from Gram-negative and Gram-positive panel testing or who used mass spectrometry-based rapid identification (21,29). While in this retrospective analysis we cannot definitively assert that the decrease in 30-day mortality is a direct result of the BC-GN test being implemented, the trend toward more timely administration of effective antibiotic therapy, the significantly decreased length of stay in the ICU, and the significantly fewer deaths associated with MDR organisms suggest that more rapid identification of Gram-negative organisms and major resistance mechanisms played an important role.…”

“…It is therefore imperative for laboratories to understand if and how such testing impacts patient outcome in order to justify its use. Compared to other studies that have used simulated samples, proposed theoretical benefits from antimicrobial interventions, and/or excluded polymicrobial cultures, this study aimed to provide a practical reference for the effects of this technology on laboratory turnaround times and patient care in a real-world hospital setting (16)(17)(18)(19)(20)(21)(22). While others have bundled rapid bloodstream infection diagnostics with improved stewardship practices for their analyses (9,17), it has been shown that antimicrobial stewardship interventions for Gram-negative bacteremia alone can improve outcomes (23).…”

Clinical Uptake of Antimicrobial Stewardship Recommendations Following Nanosphere Verigene Blood Culture Gram-Negative Reporting

“…Rapid identifi cation of GN bacteremia and key susceptibility markers can lead to many benefi ts, such as earlier deescalation of empiric therapy and switch to appropriate targeted antimicrobials that can lead to better patient outcomes, decreased length of hospital stay, and decreased overall hospital costs (9)(10)(11)(12). Th e Verigene BC-GN assay has two major advantages favoring its routine use: a random-access format with very limited handson time and the ability to rapidly provide clinically actionable therapeutic information to physicians.…”

Potential Impact of Rapid Blood Culture Testing for Gram-Positive Bacteremia in Japan with the Verigene Gram-Positive Blood Culture Test

“…The Verigene Gram-positive blood culture assay (BC-GP) (Nanosphere, Inc., Northbrook, IL) is a sample to result microarray system for identification of common Gram-positive bacteria and major resistance markers directly from positive blood culture. Although a number of studies have previously evaluated BC-GP reporting performance ranging from 92 to 99% agreement with conventional methodology [12–16], one limitation of previous reports has been that many of the studies have been from the United States as well as countries outside of Japan with only one published report of limited scope in Japan [17]. …”