NEW YORK (GenomeWeb) – Led by researchers at the Hospital Ramón y Cajal in Madrid, an international team has demonstrated that Cepheid's Xpert-Carba-R test had high sensitivity, specificity, and positive and negative predictive values for detecting patient colonization with carbapenem-resistant enterobacteriaceae using both rectal swab and contrived samples.
The results of the study, published in the Journal of Clinical Microbiology late last month, suggest that Cepheid's assay could be used as part of a larger screening program for CRE, according to one of the study's authors.
Cepheid's CEO John Bishop commented during a call to discuss the firm's first quarter earnings that the Carba-R test is "evolving into both a diagnostic and a surveillance opportunity," noting that the firm expects some customers to introduce screening programs amongst high-risk patient populations in areas that have seen outbreaks of carbapenemase-producing organisms.
In the JCM study, the investigators evaluated a combined 383 clinical samples from two US sites — the David Geffen School of Medicine at UCLA and the Westchester Medical Center in Valhalla, New York — as well as Central Manchester University Hospitals NHS Foundation Trust in the UK and Hospital Ramón y Cajal in Madrid. The study also looked at 250 contrived samples, including spiked-in carbapenemase-producing organisms and negative controls.
The Carba-R results were compared to results of culture followed by sequencing.
Xpert Carba-R tests for the DNA of carbapenemase-producing organisms and was updated last year to include additional resistance gene family targets. The incidence of these targets varies globally. The test detects the KPC, NDM, VIM, OXA-48, and IMP-1 gene families, and it was recently cleared by the US Food and Drug Administration.
"The sensitivity, specificity, but most importantly the negative and positive predictive values, are pretty nice," particularly considering the requirements for a screening test, Rafael Cantón, chief of the microbiology service at the Instituto Ramón y Cajal de Investigación Sanitaria and corresponding author on the study told GenomeWeb in an interview.
Specifically, sensitivity and specificity compared to sequencing were about 97 and 99 percent, respectively. The PPV was 95 percent, while the NPV was 99 percent.
The utility of the test would ultimately depend on local epidemiology, Canton said, but it covers "the most important carbapenemases," and, among the four institutions included in the study representative of various international settings, these results were encouraging.
The results are also interesting in light of a previous analysis of a different molecular CRE test— the research-use-only Check-Direct CPE from Dutch firm Check-Points — that showed low positive predictive value and resulted in researchers expressing concerns over its potentially being used for screening.
Cantón said the team had not evaluated the CheckPoints test, but it is currently studying a loop-mediated isothermal amplification test from German firm Amplex and preliminary results are "comparable" to the Cepheid test.
The latter test is also rapid, as is the Xpert Carba-R, which is an important criterion for a screening assay. The Carba-R test took about 47 minutes to run, according to the study.
Results in less than one hour are important if clinicians have to make decisions about where to place patients and whether or not to isolate them.
The group chose to do the study at many different institutions to capture the varying epidemiology around the world. Cantón said the groups were chosen by reputation and publication record.
"In the US, you have more KPCs, but now spreading in Europe we have OXA-48, so it was interesting to have different institutions to cover all the targets of the test," he noted.
The test is currently recommended for rectal swabs, but Cantón noted that there is literature suggesting it may be useful in the future for other sample types, such as abdominal or respiratory.
The comparator testing was admittedly in-depth, as culture alone would be a suitable "gold standard." But the group chose to sequence as well, to determine the identity of the positive samples.
There were six samples that were positive by the reference method but negative on the Carba-R test. However, there were also 18 samples that were negative using combined culture and sequencing but positive for at least one target on the Cepheid test. Eleven of these were considered true positive after discrepant analysis was performed.
Notably, the reference method — including culturing, amplification, and sequencing — can take days, so it is not so useful to triage patients. But with a one-hour test, patients could be screened and isolated more readily, or could be classified as a potential risk to have an infection later, Cantón said.
The study did not perform any economic modeling, but Cantón said that the test will likely improve decision-making and patient care and it could save number of days a patient is admitted. A similar evaluation of the Cepheid test for Clostridium difficile showed screening patients using that test had the potential to save on costs.
Cantón's lab will continue to use the test, but not yet as a screening test for all patients as the cost is still too high in his location in Spain. The test will be used for routine testing and outbreak monitoring, however.
Depending on cost and epidemiology, this may change. "If the price went down, we would use more of the tests," Cantón said, noting that the local epidemiology, cost of unnecessary isolation, and the risk of carbapenemase spread in cases that aren't tested are other important factors hospitals must weigh.