July | August 2006 | Hospital-acquired infections are a major contributor to patient morbidity and mortality and remain a serious problem for the healthcare industry. Accordingly, there is increasing demand for rapid and reliable tests for important pathogens, such as MRSA (methicillin-resistant Staphylococcus aureus), the most common antibiotic-resistant pathogen. MRSA is associated with increasing medical costs, hospital stays, and deaths.
Tests for pathogens increasingly rely on genomic methods that identify specific genetic signatures of bacteria or viruses. A good example is found in Cepheid’s GeneXpert system. GeneXpert combines automated sample preparation with real-time PCR (polymerase chain reaction) amplification and detection for automated nucleic acid analysis. The system purifies, concentrates, detects, and identifies targeted nucleic acid sequences in under an hour for selected assays. Cepheid’s IDI-MRSA test specifically detects MRSA directly from a single nasal swab specimen.
Rapid detection of other pathogens provides the potential for significant impact on the healthcare industry. Cepheid has recently announced the release in Europe of the Xpert EV (enterovirus) assay for clinical diagnostic use on the GeneXpert System. The Xpert EV assay is designed to facilitate the detection of EV-associated meningitis. Enteroviruses cause 90 percent of all viral meningitis cases. While viral meningitis typically self-resolves, bacterial meningitis is potentially fatal. Currently, patients who present with meningitis symptoms undergo treatment for bacterial meningitis until culture-based test results are available, generally in two to three days. Rapid molecular diagnosis of the viral disease could avoid unnecessary use of antibiotics and could be of benefit to both the patient and the community because of its impact on health economics and the problem of developing drug resistance to antibiotics. The Xpert EV assay detects EV RNA in cerebrospinal fluid by RT-PCR in less than three hours. Such rapid results may assist in determining antibiotic use and hospitalization decisions, and may help reduce the utilization of other more expensive diagnostic modalities such as MRIs, CTs, and X-rays.
Cepheid is collaborating with the Foundation for Innovative Diagnostics (FIND), a Geneva-based nonprofit organization, to develop a rapid molecular diagnostic test for bacterial tuberculosis (TB) that will also run on the GeneXpert system. Today’s standard culture method for TB detection takes several weeks to generate results and is frequently inaccurate. Funded by the Bill and Melinda Gates Foundation, FIND aims to facilitate the application of technological innovations to develop affordable diagnostic tests for diseases affecting developing countries. The text will detect TB mycobacteria in sputum and simultaneously determine whether the organisms are drug resistant. The spread of TB has been exacerbated by the large number of global travelers, worldwide rise of multidrug-resistant TB strains, and the global spread of HIV — which markedly increases susceptibility to tuberculosis and is also an increasing health issue for developed nations.
Rapid tests need not be based on genomic methods. Accelr8 Technology is a privately funded startup based in Denver that is developing rapid tests for bacterial pathogens based on imaging and microfluidic technology. Accelr8 has focused on proprietary surface technologies that allow them to capture and image the growth of individual bacterial colonies.
The BACcelr8r bacterial analyzer is designed to identify, count, and provide complete antibiotic susceptibility data on bacterial species within a few hours of sample injection without prior culturing. It is composed of a benchtop instrument and disposable microfluidic cartridges. The cartridges make use of Accelr8’s OptiChem surface chemistry. In the fluidic channels, the surface chemistry minimizes loss of bacteria prior to entry into the analysis chamber. In the chamber itself, the surface is activated to bind and immobilize the bacteria. The OptiChem surface chemistry provides low background and high signal strength, which is critical when analyzing complex biological fluid samples.
The BACcelr8r instrument makes use of automated microfluidics and digital microscopy and image analysis software. Model experiments have shown that the prototype system can provide results for bacterial species identification and viable counts in two hours or less, and antibiotypes in eight hours or less.
E-mail Robert M. Frederickson at email@example.com.