Rapid molecular diagnosis of urinary tract infection will soon enable individualized, evidence-based selection of antibiotics "right at the point of care," according to Dr. Joseph C. Liao. "Currently we rely on urine culture, which takes 2-3 days at a central microbiology laboratory," he said. "What if in the future [you] could obtain molecular diagnosis in less than 1 hour right there in your office? And what if we could tailor the choice of antibiotics for the patient sitting in your office [rather than start broad-spectrum antibiotics empirically]?"
Personalized, evidence-based selection of antibiotics has become an increasingly important goal – for both individual and public health – as the problem of antibiotic resistance has intensified, said Dr. Liao and other speakers at the annual meeting of the American Urological Association.
Over the past several years, Dr. Liao and his colleagues in the urology department at Stanford (Calif.) University have used biosensor technology to develop an assay for rapid pathogen identification, as well as a biosensor-based antimicrobial susceptibility test for urinary tract infection (UTI). "We’ve been able to achieve pathogen identification within an hour, and antimicrobial susceptibility testing within 3 hours," Dr. Liao reported.
The biosensor (a molecular sensing device that generates a measurable signal in the presence of a target analyte) is already part of everyday clinical practice, he noted. The glucose sensor and the i-STAT portable clinical analyzer, for example, are commonly used biosensor-based devices. The biosensor being utilized in the "next generation" of UTI diagnostic tools is comprised of a chip about the size of a microscope slide with 16 individual sensors. "Like computer technology, it can be mass produced at a relatively low cost," said Dr. Liao, who is also chief urologist at the Veterans Affairs Palo Alto (Calif.) Health Care System.
The overall strategy for pathogen identification involves lysis of the bacteria present in a urine sample, followed by a hybridization process that enables the sensor to detect bacterial 16S rRNA, a kind of "bacterial molecular fingerprint." This results in a signal output. "Essentially, we’re converting a molecular hybridization event into an electrical signal," Dr. Liao explained. "And the higher the bacterial concentration, the higher the signal."
Bacterial 16S rRNA is also a marker of bacterial growth, a property that Dr. Liao’s research group has exploited to develop a biosensor-based antimicrobial susceptibility test (AST). By incubating a urine sample in the presence or absence of commonly used antibiotics, and quantifying the 16S rRNA level, "we can follow the differential growth and derive the AST," he said. Dr. Liao and his colleagues recently completed a clinical validation study in which they compared results from their biosensor platform with results from standard microbiological analysis in more than 200 urine samples collected from patients at the Spinal Cord Injury Service at the Veterans Affairs Palo Alto system. Pathogen detection sensitivity and specificity were 92% and 97%, respectively, and "in corresponding AST, we found an overall agreement of 94%," said Dr. Liao, whose study was published early this year (J. Urol. 2011;185:148-53).
In the future, Dr. Liao hopes to use biosensor technology to also detect biomarkers that are shown to be indicative of infection in the presence of pathogens, he said. Such an integrated assay would detect both biomarkers and pathogens, and thus address the host immunity response as well as identify the pathogen. This could further improve the now-challenging task of differentiating colonization, simple UTI, and early complicated UTI, "and [could] help us better differentiate and stratify the severity of infection," he said.