NEW YORK (GenomeWeb) – In a five-year study, the Verigene gram-positive blood culture panel enabled more effective management of antimicrobial therapy by detecting the presence or absence of genes reflecting resistance to antibiotics, according to clinicians at the Children’s Hospital Los Angeles (CHLA).
The authors said that the Luminex Verigene gram-positive blood culture (BC-GP) panel performed better than traditional susceptibility testing methods in two important areas — it reduced the time to identify pathogens causing bloodstream infections and, importantly, the time to detect organisms' genotypic resistance to antibiotics by between 24 and 48 hours.
The findings from a large study published recently in the European Journal of Clinical Microbiology & Infectious Diseases show the effectiveness of MDx tests, such as Verigene, in helping reduce overprescribing of broad-spectrum antibiotics, Jennifer Dien Bard, an author of the study and director of microbiology and virology at CHLA, said in an interview.
Dien Bard noted that as a result, clinicians can depend on the use of genotypic resistance detection to forecast phenotypic resistance in patients with staphylococcal or enterococcal bacteremia. Such testing, she added, could mitigate the need to wait until full susceptibility results are available to de-escalate the use of therapies.
The authors used the Verigene panel — which detects 12 gram-positive targets and three resistance markers — to test 1,636 blood culture bottles positive for a gram-positive organism. They found that the panel's positive percent agreement for methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis were in alignment with that of conventional antimicrobial susceptibility testing.
Dien Bard and her colleagues noted that with implementation of the Verigene gram-positive blood culture panel, clinicians at their hospital reduced the median length of stay for patients admitted to general pediatric units by 1.5 days and the median hospital cost per patient by $3,757. Clinicians identifying and treating S. aureus bloodstream infections reduced the median length of stay by 5.6 days and hospital cost per patient by $13,341, they said in a paper published in 2016 in the Archives of Pathology & Laboratory Medicine.
They saw the greatest savings among patients with S. aureus bacteremia who didn't have co-morbidities. Patients with significant co-morbidities produced little savings, because the length of stay is often inherently long, Dien Bard said.
Commenting on the five-year CHLA study, Sherry Dunbar, senior director, global scientific affairs at Luminex, said, "[W]ith the emergence of antibiotic resistance, clinicians need to be sure they can trust the accuracy of the rapid result, so they can rely on it for choosing treatment interventions that positively affect patients."
She said that by demonstrating accuracy and proven performance over a long period of time, the Verigene bloodstream panel enables clinicians to "have high confidence in the results, enabling them to make faster and more informed treatment decisions for their critical patients.”
Trusting the MDx result
When CHLA, a pediatric academic medical center, implemented the Verigene panel more than five years ago, its clinicians at first hesitated to de-escalate antibiotic therapy even when the test results indicated that they should, Dien Bard said, due to the serious nature of the infections they were treating in the pediatric setting. The mortality rate of patients with sepsis, for example, rises rapidly for every hour that a patient is untreated.
In general, when patients are suspected of having bacteremia or sepsis, clinicians immediately prescribe a broad-spectrum antibiotic aimed at killing most bacteria known to cause the infection. They start de-escalating use of the drugs when they deem it appropriate. Not only does that reduce the impact of prescribing a less effective antibiotic and mitigate against driving up resistance to the drug, it also means the patient is getting a more effective antibiotic, Dien Bard said. Deescalating to a more targeted antibiotic, such as cefazolin or oxacillin, is efficacious because it optimizes treatment for patients with a methicillin-susceptible Staphylococcus aureus (MSSA), she said. A clinician would switch, in this case, from prescribing vancomycin, a broad-spectrum antibiotic.
Traditional susceptibility testing, however, can take longer than is optimal, requiring about 20 to 24 hours to identify the pathogen and an additional 18 to 24 hours to test for susceptibility. "That's when the process is straight forward and we don't have to do repeat testing for some reason," Dien Bard said.
CHLA implemented the Verigene system and panel primarily because of its ability to predict susceptibility based on the presence or absence of resistance markers, such as mecA or vanA/B gene. "We wanted to provide rapid, actionable results rather than having to wait days for a traditional susceptibility result," she said.
The panel also identifies coagulase-negative staphylococci that are usually contaminants obtained from a patient's skin at the time of a blood draw, and that can enable clinicians to discontinue antibiotics if the patient is stable and the clinician is comfortable that an infection is not present.
The decision to implement the Verigene test also had to do with its availability to perform gram-positive blood culture testing for bloodstream infections more than five years ago. Further, being able to choose one kit for gram-positive testing rather than a more expensive system that offered a broader panel factored into the decision, Dien Bard said. "It can be very difficult to bring on a new test," she said, "because you have to justify the increased cost, and it is not necessarily going to reduce your workload. However, [the Verigene panel's] clinical importance and expected cost savings justified bringing it on."
The Verigene gram-positive blood culture panel was developed by Nanosphere, which Luminex acquired in June 2016 for about $90 million.
Luminex said recently that it has begun clinical trials for a next-generation Verigene II system and gastrointestinal panel. Clinical trials for its Verigene II respiratory panel trial will commence during the 2018-2019 flu season, and the firm anticipates introducing blood culture panels for Verigene II soon after the launch of this first set of panels.
Health providers have available an increasing number of molecular platforms to test for bloodstream infections. Among Verigene's closest competitors, the BioFire Filmarray blood culture ID panel provides "excellent performance," Dien Bard said.
A blood culture identification and susceptibility kit from Accelerate Diagnostics "is promising in that it is the first to provide a true susceptibility result," she said. "It's giving you a true interpretation that can be used to select specific drugs. The Verigene and BioFire panels are providing genotypic resistance detection. Therefore, you are looking for a gene only, which can be very helpful for gram positive pathogen detection."
The Accelerate kit provides pathogen identification from a positive blood culture in around 90 minutes and a susceptibility result within 7 hours.
"The biggest benefit of the Accelerate system is in determining antimicrobial susceptibility of gram-negative pathogens," she said. Its use of a proprietary method to monitor how live cells interact in response to different concentrations of drugs along with a mathematical calculation to determine the minimum inhibitory concentration of each drug ensures that the firm's Pheno bloodstream infection kit also flags pathogens affected by other mechanisms of resistance, she noted.
Researchers continue to press forward in search of faster ID-AST solutions.
A proof-of-concept study published in Clinical Chemistry earlier this month has shown that using a sped-up PCR method, high-resolution melt analysis and a technique to detect bacteria in their demise after a brief antibiotic treatment can yield full ID-AST results in around eight hours, with the potential to go even faster.
"Molecular testing has been instrumental in changing how the lab works in the past few years," Dien Bard said. "It is worth noting that neither the Filmarray nor Verigene test covers all pathogens or resistance mechanisms. Traditional susceptibility testing is not becoming obsolete in any way."