FDA issues press release following clearance of a clinical lab test to detect genetic markers that indicate the presence of Carbapenem-resistant Enterobacteriaceae

Clearance by the US Food and Drug Administration (FDA) of a new rapid, multi-marker genetic test designed to identify bacteria that are resistant to Carbapenem antibiotics was considered significant enough that the federal agency issued a press release announcing that the test was cleared and now available for use by physicians and clinical laboratories in the United States.

In the race to develop molecular assays and genetic tests for infectious disease that deliver improved sensitivity and specificity with a faster time-to-answer, this new test offers all three benefits. Results are available in just 48 minutes, for example.

It was on June 29, 2016, that the FDA cleared Cepheid’s Xpert Carba-R rapid-diagnostic test for marketing in the United States. This is the first clinical laboratory test cleared for market by the FDA that detects healthcare-associated infections (AKA, hospital-acquired infections or HAIs) through the use of genetic markers taken directly from clinical samples. The assay tests for genetic markers that indicate the presence of Carbapenem-resistant Enterobacteriaceae (CRE).

The FDA cleared Xpert Carba-R for use with pure bacterial isolates. However, the new clearance involves use with direct rectal swab specimens. This reduces the time needed to detect the five major gene families that are indicative of antibiotic-resistant (AR) bacteria to just 48 minutes.

Alberto Gutierrez, PhD, is Director of the FDA’s office of In Vitro Diagnostics and Radiological Health (OIR) within the Center for Devices and Radiological Health (CDRH). In the FDA’s news release, Dr. Gutierrez stated, “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.”

The Carba-R assay requires less than one minute of hands-on time to process the specimen and load the cartridge. The GeneXpert system automates the majority of the testing process. In a Cepheid press release, David Persing, MD, PhD, Cepheid’s Chief Medical and Technology Officer, noted the time savings. “In contrast,” he stated, “traditional enriched culture methods typically take 3-5 days.” This drastic reduction in time-to-answer illustrates how genetic sequencing and automation could drive many innovations brought forth as precision medicine matures.

The Xpert Carba-R assay is 1 of 20 In Vitro (IVD) tests available in the US on Cepheid’s GeneXpert platform. As systems grow further, automation of sequencing and complex diagnostics will increase the rate at which clinical laboratories can expand offerings, perform tests, and return results. As costs drop, access to advanced testing and automation for smaller labs will continue to improve.

Precision Medicine Helps Medical Laboratories, Clinicians Combat AR Threats

The March, 2016, Morbidity and Mortality Weekly Report (MMWR) highlighted a Centers for Disease Control and Prevention (CDC) study into antibiotic resistant (AR) infections in US healthcare facilities. Researchers tested isolates for six common AR threat pathogens. The resulting data, reported from more than 5,500 acute care, long-term care, and inpatient rehabilitation facilities in 2014, identified CRE as the leading cause of healthcare-associated infections.

In a Cepheid press release, Paul Schreckenberger, PhD, Director of Microbiology at Loyola University Medical Center in Maywood, Illinois, discussed the benefits molecular diagnostics offer laboratories, healthcare providers, and patients in combating AR threats. “The availability,” he stated, “of a rapid and accurate molecular test for the most prevalent mechanisms of carbapenem resistance represents an important addition to the limited tools the laboratory has available to fight the emergence of multidrug resistant organisms, like CPOs [carbapenemase-producing organisms].”

Paul Schreckenberger, PhD (above), is Director of Microbiology at Loyola University Medical Center in Maywood, Illinois. In the Cepheid press release, Dr. Schreckenberger stated that “Knowing which carbapenemase gene is present in a resistant isolate helps the hospital identify and manage outbreaks, and can also be valuable for monitoring the spread of multi-resistant bacteria among hospital populations considered most at risk." (Photo copyright: Cap Today.)

Paul Schreckenberger, PhD (above), is Director of Microbiology at Loyola University Medical Center in Maywood, Illinois. In the Cepheid press release, Dr. Schreckenberger stated that “Knowing which carbapenemase gene is present in a resistant isolate helps the hospital identify and manage outbreaks, and can also be valuable for monitoring the spread of multi-resistant bacteria among hospital populations considered most at risk.” (Photo copyright: Cap Today.)

The 2015 National Action Plan for Combating Antibiotic-Resistant Bacteria (CARB) also emphasizes the role innovations and new technologies will play in improving the outcome of future AR infection cases. In Goal 3 of the action plan, authors note the importance of point-of-need diagnostics and sequencing technologies capable of determining the antibiotic-resistance profiles of potential threats.

Future Precision Medicine Challenges for Clinical Laboratories

Market clearance for the Cepheid assay is one more step toward widespread use of the technologies that the action plan authors believe will drive the future of healthcare. Programs such as the FDA’s precisionFDA web platform, and President Obama’s Precision Medicine Initiative, are helping to draw attention to and build the foundation for personalized medicine.

However, pathology groups and medical laboratories still must convince payers of the value of these new—and sometimes expensive—tests and procedures. (See Dark Daily, “Failure to Pay for New Molecular CPT Codes Created Money Crisis for Clinical Laboratories and Pathology Groups,” April 30, 2013.)

Nevertheless, earlier this year, oncology test providers made significant progress in earning the approval of private insurers. (See Dark Daily, “Genetic Tests and Precision Medicine Start to Win Acceptance by Some Payers; Pathologists and Clinical Laboratories Have Opportunity as Advisors,” March, 14, 2016.)

Despite these gains, it remains essential for clinical laboratories and IVD companies to work with payers to define evidence requirements. Another important task is to educate physicians on how to identify patients who would benefit from such lab testing.

—Jon Stone

Related Information:

FDA Approves Xpert Carba-R Assay for Detection of Carbapenem Resistance Genes

FDA Supports Expanded Claims for Xpert Carba-R Test for ‘Superbugs’

FDA Clears First Test to Detect Specific Genetic Markers for Certain Antibiotic-Resistant Bacteria Directly from Clinical Specimens

Xpert Carba-R Assay for the Detection of Carbapenemase-Producing Organisms in Intensive Care Unit Patients of a Korean Tertiary Care Hospital

Vital Signs: Preventing Antibiotic-Resistant Infections in Hospitals—United States, 2014

National Action Plan for Combating Antibiotic-Resistant Bacteria

FDA Clears Test for Genetic Markers of Antibiotic Resistance

FDA Clears First Genetic Marker Test for Antibiotic-Resistant Bacteria

Xpert Carba-R Brochure

Genetic Tests and Precision Medicine Start to Win Acceptance by Some Payers;
Pathologists and Clinical Laboratories Have Opportunity as Advisors 

Failure to Pay for New Molecular CPT Codes Created Money Crisis for Clinical Laboratories and Pathology Groups