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They’re called health care-associated infections (HAI), and the most notorious of them—methicillin-resistant staphylococcus aureus (MRSA)—has been on the rise within the nation’s hospitals every year since 1970.
This year, nearly 2 million patients will contract an infection in a US hospital; about 90,000 of them will die from it. HAI diagnosis and treatment add about $5.7 billion to health care costs annually. While up to 30% of HAIs are considered preventable, the other 70%—MRSA and other bacterial “superbugs”—have proven resistant to at least one antibiotic.
Hospitals are fighting back by increasing frequency of testing, especially among high-risk groups, including the very young, the elderly, patients with compromised immune systems, and those suffering from cystic fibrosis and respiratory illnesses. Some facilities are now screening all admitted patients. The Veterans Administration (VA) has also mandated expanded testing of all patients for MRSA, a more treatable strain, and others.
The diagnostics industry is responding with a range of tests, depending on the extent and severity of the symptoms. Options include skin biopsy culture of the infected site, blood culture, sputum culture through coughing or a bronchoscopy, or a urine culture.
One-Hour MRSA Detection
Cepheid, Sunnyvale, Calif, recently received FDA clearance to market its Xpert MRSA test. Developed to run on the company’s GeneXpert System, the test offers detection of MRSA bacteria infections in approximately 1 hour, according to David Persing, MD, PhD, who is Cepheid’s executive vice president and chief medical and technology officer.
The Xpert MRSA test is a molecular test that uses polymerase chain reaction (PCR) genetic amplification technology. Rather than growing intact organisms, the Cepheid test uses DNA-copying enzymes that amplify an MRSA organism’s signature sequence. “The real advantage is speed,” Persing says. “Bugs take days to grow, but PCR takes only minutes to amplify and identify the signature.”
Persing says a turnaround time of 1 to 2 hours for the MRSA test is fast enough for preadmission testing and to use for screening admissions coming into an intensive care unit and from emergency rooms.
MRSA results are generated from a swab in 72 minutes. Tests can be performed on demand and around the clock. “Other PCR technologies are done in batches, usually one time a day and twice at most,” Persing says. “As a result, what is really a 2-hour analytical procedure ends up being more like a 20-hour turnaround time on weekdays, and 40 hours on weekends.”
Persing says that real-time PCR as a technique has not translated into real-time patient results.
Cepheid is now working with hospitals and VA facilities across the United States to make its rapid Xpert MRSA test available. The VA has mandated MRSA surveillance programs in all its hospitals for all patients.
Xpert tests are currently approved for other “need for speed” indications, Persing says. Xpert GBS is for rapid testing for Group B streptococcus, a bacterial infection that puts newborns at risk. Cepheid’s Xpert EV is the first molecular test approved for the management of meningitis, another condition for which treatment or management decisions hang in the balance.
“We are especially excited about making GeneXpert technology available for patients with hospital-acquired pneumonia and other serious infections where results are actionable and time-critical, Persing says. “Our test for detection of TB and rapid determination of drug resistance is starting alpha testing in a few months, as is a rapid test for influenza.”
While the rapid Xpert MRSA is an important step forward in how hospitals conduct screening and make real-time decisions about patient isolation and management, the ultimate value of the MRSA test and its coming methicillin-sensitive staphylococcus aureus (MSSA) test rides on their ability to rapidly determine which drug therapy to use, Persing says.
The planned influenza test, which will provide results from a nasal swab in 30 to 40 minutes, will indicate drug susceptibility of the particular influenza virus the patient is carrying, Persing says. “That way, a patient can leave the clinic with the right drug, which is more effective for them individually and for reducing transmission to others.”
In fighting MRSA and other HAIs, Persing says, most hospitals decide on one technology; a few will choose rapid testing and supplement it with broth-enriched culture—a process that can take 4 to 5 days and is recognized as the gold standard.
“We think the MRSA test is the right technology at the right time, and many hospitals appear to agree,” he says. “Interestingly, the Xpert MRSA may be the first molecular test that many hospitals perform, because it is very easy and does not require a specialized molecular diagnostics facility or staff.” Persing adds that even hospitals without molecular labs have infection-control issues that the GeneXpert platform can address.
3M Test Coming to United States Next Year
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- 3M BacLite system
It appears that FDA 510(k) submission and clearance is the only barrier 3M, St Paul, Minn, still needs to overcome before launching its 3M BacLite system for MRSA in the US market. That should come later this year or in early 2008.
The culture test, available now in Europe, is the most cost-effective of any MRSA tests delivering same-day results, the company says. Brian Anderson, global marketing operations manager for 3M Medical Diagnostics Clinical Lab Products, says the BacLite system can confirm a negative result within 5 hours and a positive result within 24 hours.
The system uses ultrasensitive AK Rapid technology to detect MRSA and other dangerous infections. “AK technology measures adenylate kinase activity,” Anderson says. “Adenylate kinase, an essential housekeeping enzyme found in all cells, is a highly sensitive cell marker. By supplying purified ADP in vitro, the amplified levels of ATP produced can be measured using bioluminescence.”
The BacLite system is the result of the company’s recent acquisition of Acolyte Biomedica Ltd, the UK-based company that developed the test. The rapid 3M MRSA test made its debut in the UK in 2006. It was launched this past March in Europe at the 17th European Congress of Clinical Microbiology and Infectious Diseases.
On another front, 3M is partnering with Gen-Probe, San Diego, to develop a separate platform to commercialize rapid, easy-to-use nucleic acid tests for identifying MRSA and other dangerous HAIs.
Nontraditional Approaches to MRSA
Beyond the United States, researchers are pushing ahead with a number of newfangled techniques for identifying risky bacteria such as MRSA and its possible spread.
The UK is a real hotbed of activity. At the University of Warwick’s Center for Cognitive and Neural Systems, Prof Julian Gardner and staff have studied how effectively their electronic nose, or e-nose, can sniff out MRSA and other bacteria. Dean of Warwick’s engineering school, Gardner has been developing the e-nose for more than 17 years.
The size of two desktop PCs, the system consists of a commercial 32-element conducting polymer electronic nose. It analyzes gas samples by passing the gas over an array of electrodes coated with different conducting polymers. Each electrode reacts to particular substances by changing its electrical resistance in a distinct, plottable way. Combining all the electrodes’ signals produces a “smell print” of the chemicals—a mixture the e-nose’s software can learn to recognize.
As impressive as the e-nose’s reported 96% success rate in screening patients for bacterial type infections are reports that the electronic sniffer could produce dependable test results in as little as 15 minutes.
In the United States, NASA developed an electronic nose to detect pollutants inside spacecraft to prevent the buildup of potentially lethal concentrations. The food and beverage industry has used electronic noses in quality-control applications for many years.
BD’s Rapid and Culture Test Options
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- BD GeneOhm MRSA
Becton Dickinson and Company (BD), Franklin Lakes, NJ, provides two FDA-cleared MRSA tests to aid in prevention and control of HAIs. The company’s simplified test, the BD GeneOhm MRSA assay, is a qualitative in vitro test for direct detection of nasal colonization by MRSA, according to Glen MacKenzie, director of marketing, GeneOhm.
Here’s how it works: With a specimen obtained directly from a patient’s nose, the assay uses PCR technology to amplify DNA and detect unique MRSA gene sequences. A simple and efficient bacterial lysis procedure is then followed by the real-time PCR to detect MRSA.
A PCR thermocycler, a commercially available instrument, is then used to amplify MRSA genetic material if present. “Dedicated software interprets the data into a definitive assay result, generating positive and negative results that are displayed on a computer screen,” MacKenzie says.
The BD GeneOhm assay offers a 2-hour turnaround for screening incoming patients as MRSA carriers, a faster and more sensitive method than 1- to 3-day traditional culture testing.
“Because of the speed, patients who test positive are identified quickly, and infection control procedures are implemented earlier,” MacKenzie says. Identifying MRSA when patients are admitted to a facility is critical to preventing its spread and to preventing MRSA infections in other patients. Customers using the BD GeneOhm MRSA assay report dramatic reductions in the number of MRSA blood stream infections, MacKenzie says. “Batching the specimens and running the assay a couple of times a day makes for efficient use of technologist time, and minimizes the number of unisolated patient days annually.”
The BD culture test for MRSA—the BBL CHROMagar MRSA Test—provides for the detection of MRSA using chromogenic substrates and a cephalosporin. MRSA strains will grow in the presence of antibiotics and produce mauve-colored colonies resulting from hydrolysis of the chromogenic substrates.
In clinical evaluations, BBL CHROMagar MRSA Test displayed 8% greater recovery of MRSA than traditional screening algorithms with the ability to identify MRSA earlier than most traditional algorithms, according to Mackenzie. “This technology requires less technologist time than traditional cultures and improves laboratory workflow compared to traditional culture,” he says. The BBL CHROMagar MRSA Test allows for the direct detection and identification of most MRSA within 24 hours, or 48 hours with a confirmatory test.
bioMérieux: Tests Suggest Treatments
bioMérieux’s BacT/Alert 3D |
bioMérieux’s Vitek 2 |
bioMérieux’s, Durham, NC, BacT/Alert 3D is an automated testing system that determines whether or not bacteria are present (positive or negative). The Vitek 2 is an instrument for the rapid identification and susceptibility testing of bacteria and yeasts. If the BacT/Alert 3D indicates bacteria are present, the Vitek 2 identifies the bacteria as MRSA, acinetobacter, or something else, and provides a listing of drugs to which the bacteria are resistant. While the Vitek 2 is a culture test, automated testing yields results in 6 to 10 hours—significantly sooner than manual approaches that can require up to 2 days.
bioMérieux also supplies a microbial genotyping system (DiversiLab) capable of tracking specific strains to give an early sign of a potential outbreak.
Killing Bacteria with Copper
A Birmingham, England, hospital changed its fittings from stainless steel to copper after university trials showed that copper proved a safer choice to prevent the spread of MRSA and other antibiotic-resistant bacteria. The trials showed the antimicrobial properties of copper and its alloys quickly suffocated superbugs.
Concerned that 80% of MRSA transmissions are via surface contacts, one UK facility is using copper for door handles, push plates, bath taps, toilet handles, and grab rails. Even the staff lockers will be copper alloy.
Lab studies found that while MRSA bacteria remained active for days on stainless steel, on brass they died in less than 5 hours, and pure copper surfaces suffocated the germs in 30 minutes.
Finally, researchers at Manchester University, UK, found that when they turned free-range larvae from maggots loose on diabetic patients with MRSA-infected foot ulcers, the insects cleared up the infections in 12 of 13 patients. Researchers suspect the maggots could prove valuable in treating MRSA infections in other body locations.
Nicholas Borgert is a contributing writer to CLP.