FDA Clears First Test to Detect Genetic Markers for Resistant Bacteria Directly From Clinical Specimens

Assay targets carbapenem-resistant Enterobacteriaceae

The FDA has cleared for marketing the Xpert Carba-R Assay (Cepheid), an infection-control aid that tests patient specimens to detect specific genetic markers associated with bacteria that are resistant to carbapenem antibiotics, which are widely used in hospitals to treat severe infections. These resistant organisms are commonly referred to as carbapenem-resistant Enterobacteriaceae (CRE) and have been reported in almost all U.S. states.

“By using a specimen taken directly from a patient to test for the presence of genetic markers, hospitals can more quickly identify these dangerous bacteria resistant to certain antibiotics,” said Alberto Gutierrez, MD, director of the FDA’s Office of In Vitro Diagnostics and Radiological Health at the Center for Devices and Radiological Health.

Current methods to identify colonization with CRE or other resistant organisms rely on growing bacteria from fecal material in cultures, which are then subjected to antimicrobial susceptibility testing to determine in vitro susceptibility to antimicrobial agents. Bacterial culture methods and susceptibility testing may take up to four days, and additional testing is often also required to confirm that carbapenemase, an enzyme that inactivates carbapenem antibiotics, is present. The Xpert Carba-R Assay tests specimens taken directly from patients, which are usually obtained by rectal swabs, for the presence of five genetic markers that are associated with carbapenemase, the enzyme produced by CRE.

The Xpert Carba-R Assay is intended as an aid in infection control and can be used in conjunction with other clinical and laboratory findings, according to the FDA. Although the assay tests for the most-prevalent carbapenemase genes associated with resistance to carbapenem antibiotics, it does not detect the bacteria, carbapenemase activity, or other possible nonenzymatic causes of carbapenem resistance. The Xpert Carba-R Assay tests only for genetic material.

The assay also does not detect all types of carbapenemase genes, and it is important to recover bacteria for accurately tracking the spread of carbapenem resistance. Laboratories should continue to perform standard bacterial culture in conjunction with the Xpert Carba-R Assay. In addition, concomitant cultures are necessary to recover organisms for epidemiological typing, antimicrobial susceptibility testing, and confirmatory bacterial identification.

According to the Centers for Disease Control and Prevention, CRE infections most commonly occur in people with exposure to health care settings, such as hospitals and long-term care facilities. Because of this, these types of infections often occur among patients who are receiving treatment for other serious conditions. Patients whose care requires devices, such as ventilators, urinary catheters, or intravenous catheters, and patients who are taking long courses of certain antibiotics are among those at risk for CRE infections.

CRE are usually resistant to many other antibiotics in addition to carbapenems, and several CRE outbreaks of these highly resistant bacteria have been reported in the U.S. When bacteria become resistant to carbapenems, few treatment options may remain. Some CRE bacteria have become resistant to almost all available antibiotics and present a significant public health threat.

The FDA’s decision to approve the Xpert Carba-R Assay was based on data from two clinical studies. A prospective study used rectal swabs from 755 patients in hospitals and long-term care facilities to compare results from the assay with results from reference cultures and automated real-time polymerase chain reaction (PCR) sequencing. A second study designed to test the clinical performance of the Xpert Carba-R Assay used 432 rectal swabs that were artificially prepared with specific concentrations of bacteria containing the genes detected by the test. The results of these studies demonstrated similar performance between the Xpert Carba-R Assay and the culture method.

Source: FDA; June 29, 2016.