MONTEREY, CALIF. — Clinically useful tests are on the horizon to detect changes in DNA that can alter health outcomes for patients with infectious diseases, Dr. Michael F. Murray said.
Speaking at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology, he described helpful applications of recent technology that should be available within the next 5 years or so, and some genetic testing that's being marketed now but is not clinically useful. Dr. Murray has no relationships with the companies that make the products he discussed.
An example of the type of technology that will change how clinicians diagnose, treat, and prevent infectious diseases is the AmpliChip CYP450 assay, which employs polymerase chain reaction (PCR) tests followed by microarray analysis to detect 31 genetic polymorphisms in cytochrome P450 (particularly in two genes—CYP2D6 and CYP2C19).
CYP450 is involved in the metabolism of many drugs. The AmpliChip gives clinicians a report that predicts a patient's phenotype as a poor, intermediate, extensive, or ultrarapid metabolizer for CYP2D6 and a poor or extensive metabolizer for CYP2C19. This type of technology can be put to other uses as well, explained Dr. Murray, clinical chief of the division of genetics at Brigham and Women's Hospital, Boston. “This is one of many competing platforms to use technology to rapidly understand the patient's genetics and then to make a clinical decision based on it.”
The technology is capable of delivering the report to a clinician within 8 hours of taking the blood sample, though no one currently has the system set up to deliver results that quickly, he added. Clinicians could then use that information to make clinical decisions without having to know a lot about genetics.
He described a case in which genomic medicine might have made a difference in management of pneumonia. A young woman treated in the emergency department with ceftriaxone for right upper lobe pneumonia was considered to be a low risk and sent home on an oral fluoroquinolone antibiotic. After a day without fever, she worsened over the next few days before calling 911, febrile and confused. She was intubated in the field, developed acute respiratory distress syndrome, and died in the ICU 10 days later.
Theoretically, if a DNA analysis had been done on the patient the first time she came to the emergency department with pneumonia, it might have shown quickly that she had Streptococcus pneumoniae serotype 3 bacteremia, which is associated with a poor prognosis. PCR tests of the organism could have detected genotypic susceptibility to ceftriaxone and resistance to all quinolones.
DNA tests could also establish the patient's “host susceptibility profile,” Dr. Murray said. There are a lot of candidate genes for this profile, such as surfactant B. A polymorphism in surfactant B is associated with an increased need for mechanical ventilation in adults who present with community-acquired pneumonia.
If these tests had been done, the patient might not have been sent home from the emergency department. She could have been admitted, treated with IV antibiotics and aggressive respiratory therapy, and discharged 6 days later on an oral cephalosporin.
These applications of existing genetic technology aren't up and running yet, but “it's reasonable to think that at least in 10 years, probably more like 5, maybe less,” these tools will be available clinically, Dr. Murray said.
One currently available genetic test—the Otodx aminoglycoside hypersensitivity test—offers clinicians a means of detecting a common mutation associated with aminoglycoside-induced hearing loss. Results take 2 weeks, and the test costs about $250.
The marketing company suggests that all patients being considered for aminoglycoside therapy get tested, but a 2-week wait is not clinically helpful, Dr. Murray said. Plus, the genetic epidemiology is not well understood in these cases. It's not clear whether the mutation occurs more frequently in some populations, particularly Asians, or if it's underrecognized in some populations.
“Until we know that, it's hard to recommend this test in everybody that you're going to give aminoglycosides,” Dr. Murray explained.