May 2008
Feature Story

Karen Lusky

Fast forward to the future and you may see consumers screening themselves for superbug MRSA by using their iPhones, says Paul Schreckenberger, PhD, director of the clinical microbiology laboratory and associate director for diagnostic molecular pathology at Loyola University Health System, Maywood, Ill.

He’s kidding, of course, but he does foresee molecular technology progressing to the point that testing could be done in the home where parents, for example, could find out if their son or daughter who plays sports is colonized with MRSA.

As for now, he says, there are three choices for MRSA screening in health care settings: 1) culture methods, 2) two FDA-approved PCR rapid tests (BD’s GeneOhm assay and Cepheid’s Gene­Xpert), and 3) methods involving analyte-specific reagents.

“There are homebrew assays for PCR tests for MRSA surveillance,” says Andy Guhl, vice president of health-care–associated infections, BD, San Diego. “Roche [Diagnostics], for example provides an ASR [for MRSA testing], but the lab has to go through an extensive validation process to bring up the test.”

Traditional cultures produce results in about 24 to 48 hours. Some places use selective media that select for MRSA, but that testing still requires a minimum of 24 hours to grow the organism, Dr. Schreckenberger says.

The advantage of conventional cultures is that they are cheap—they can be done for about $5, Dr. Schreckenberger notes. The disadvantage is that culture takes a minimum of 24 hours and picks up only about 80 percent of MRSA whereas the BD GeneOhm assay and Cepheid GeneXpert pick up 100 percent.

Selective MRSA agars are, however, more sensitive. In April, Thermo Fisher Scientific, Wal­tham, Mass., announced it had received FDA clearance for its Spectra MRSA, which is manufactured, distributed, and sold under the Thermo Fisher specialty brand, Remel. The test, which produces results within 24 hours, can be used for screening patients for MRSA; Remel says it has a 98.1 percent positive predictive value.

As for the two FDA-approved rapid PCR methods, GeneOhm is classified by CLIA as high complexity, thus requiring performance by a medical technologist, and GeneXpert’s cartridge-based technology is moderately complex. It can be performed in a more continuous-flow fashion by a lab technician.

The GeneXpert costs about $42 a test and Gene­Ohm about $30 a test, if you do the BD test in a batch mode, Dr. Schreckenberger says. Six or more BD GeneOhm tests have to be done at a time to beat the price of a GeneXpert, he adds.

Hospitals can use a combination of MRSA screening methods, including cultures for patients admitted in the later afternoon, and GeneOhm and Gene­Xpert, which Dr. Schreckenberger predicts many will do in the future to maximize savings. For example, hospitals could use the batch method to accommodate times of the day with the highest test volumes, and then switch to GeneXpert on evening and night shifts when specimens tend to trickle in, he says.

BD reports that most of its customers are selecting a single method of MRSA testing for admissions to the hospital. However, some hospitals are starting to use the BD GeneOhm MRSA assay for admissions, followed by use of the BD BBL Chrom­Agar MRSA plate to test patients transferred to other wards or discharged from the hospital to see if patients who initially test negative for MRSA became colonized during their stay.

BD and Cepheid are stepping ahead with their next-generation Staph products, which include PCR testing that can differentiate MRSA from methicillin-sensitive S. aureus, or MSSA.

BD’s GeneOhm StaphSR assay received clearance recently from the Food and Drug Administration to test for both MRSA and MSSA in positive blood cultures.

BD has additional claims pending with the FDA for using the StaphSR assay on wound and nasal swabs. Nasal swabs could be used to screen patients, for example, coming in for orthopedic or cardiovascular surgical procedures, Guhl says. The other claim is for wounds. “Patients who develop a postsurgical infection could be quickly tested to see if it’s MRSA or MSSA,” Guhl says. The other potential wound application is for testing patients for community-acquired MRSA when they arrive at the hospital with a skin or soft-tissue infection.

Dr. Schreckenberger says there’s no reason to believe that MSSA isn’t just as big of a concern as MRSA. He predicts, in fact, that eventually hospitals will screen patients at admission for MSSA too. “The reason people started screening programs focused just on MRSA is that the treatment is so different for that versus MSSA. But hospitals need to know everyone who has MSSA or MRSA at admission, and the same for blood and wound cultures.”

The BD GeneOhm StaphSR test also provides an opportunity to rule out coagulase-negative staph (if the assay is positive for S. aureus or MRSA), a common contaminant that causes the blood culture instruments to report a positive result.

Cepheid is in the final stages of evaluating a cartridge-based blood culture detection product for MRSA and MSSA, as well as both types of Staphylococcus in wound infections.

The assay will also detect MRSA strains that have mutated further, losing the mec gene, which confers methicillin/ oxycillin resistance, reports David Persing, MD, PhD, executive vice president and chief medical and technology officer for Cepheid, Sunnyvale, Calif.

The problem is that MRSA, known as empty cassette variant, will pop up positive on the current GeneXpert and GeneOhm PCR tests for the nares and the GeneOhm StaphSR for the blood, he says. “We have seen evidence of increasing prevalence of these empty-cassette variants among nasal carriers of Staph. We want to be prepared to differentiate those strains in infections so that patients don’t get vancomycin ... when they could get a third-generation cephalo­sporin,” which kills the organism more quickly if it’s not methicillin resistant, Dr. Persing says.

Cepheid’s new test is designed to run on demand in the same timeframe as a blood culture registers positive. BD’s StaphSR, by contrast, is a batch-based test, he says.

Cepheid hopes to get FDA approval of the new applications for blood cultures and wounds later this year. “It’s expected,” Dr. Persing says, “that the blood culture bottle and wound tests will give results in about 50 minutes. We also have an evaluation underway to use the MRSA/MSSA cartridge for nasal screening.” With these potential products in the queue, he describes it as a “good thing” that Ce­pheid’s high-throughput Infinity 48 system will be available before year’s end.

Dr. Persing predicts PCR technology for MRSA screening will also get easier to use. In fact, Cepheid is pursuing a CLIA-waived version of GeneXpert, which has potential marketability within nursing homes and long-term care facilities, where, he says, “there is a real need for improved surveillance.”

HandyLab, Ann Arbor, Mich., has developed a real-time PCR-based MRSA test ready for clinical trials but is holding off until the company sees what the MRSA market is going to do. “We would like to see some clear guidance from the Centers for Disease Control and Prevention related to MRSA hospital screening,” says Mark Powelson, vice president of sales and marketing for the company.

The HandyLab MRSA assay, similar to the Cepheid GeneXpert test, if the company pursues it, would run on a real-time microfluidic platform, which HandyLab was planning, at press time, to release this month.

Also in the MRSA testing pipeline: Inverness Medical, Scarborough, Me., has a clinical trial starting soon that will test a 15-minute point-of-care test for blood cultures that turn positive. The test uses the same technology as rapid pregnancy tests, says Norman Moore, PhD, director of clinical affairs. “You don’t need PCR for ultra-sensitivity in this application since the bacteria have naturally amplified in the blood culture bottles,” he explains.

The testing has two parts: “The first test will determine if the sample is positive for S. aureus by looking for protein A,” Dr. Moore says. “The second test determines if it is methicillin-resistant [MRSA] by looking for the penicillin-binding protein.”

As for the prospects of a handheld MRSA screening device for the nares that works like a pregnancy test, don’t hold your breath. “Right now,” Dr. Moore says, DNA amplification is the only way to get the sensitivity to detect carriers of MRSA. In the future, other technologies may be available that don’t require amplification, but we aren’t there yet.”

Related Links

• Mitigating MRSA, steps ahead of the law