The announcement by the US
Department of Health and Human Services of a $20 million prize for innovative
point-of-care rapid diagnostics has overshadowed the fact that there are
already over 100 FDA-cleared molecular diagnostic tests available in the United
States. Many of these tests are characterized as “moderately complex”, which
means that they can be performed, not just by medical technologists, but by
laboratory technicians, STAT laboratory personnel, and even nurses who have
received appropriate training and competency testing. A few for influenza
testing are CLIA waived. It now is possible to identify 17 viruses and three
bacterial species directly in respiratory samples in approximately 1 hour,
detect five species of Candida
directly from a blood sample without prior culture, or identify Mycobacterium tuberculosis and
simultaneously determine if the strain is rifampin-resistant directly from
sputum samples in less than 2 hours. Molecular diagnostics are widely used to
differentiate methicillin-susceptible from methicillin-resistant Staphylococcus aureus strains directly
from blood culture vials in approximately 1 hour. Molecular assays can also determine if a
woman in labor is colonized with Group B streptococci in approximately 45
minutes directly from a vaginal/rectal swab to guide decisions on prophylaxis
to prevent neonatal sepsis. In Europe, a
novel assay can detect 91 different carbapenem-resistance genes representing five
families of beta-lactamases (KPC, VIM, NDM, OXA-48, and IMP-1) directly from a
rectal swab sample in 48 minutes to aid infection control decisions.
The question of how to justify the
increased cost of rapid diagnostic tests compared to traditional culture
methods often arises. In response, health econometric studies have been
undertaken and show that rapid detection of MRSA from blood cultures, Clostridium difficile from stool
samples, and M. tuberculosis from
sputum samples are all highly cost-effective even in low prevalence settings. Perhaps one of the greatest examples of how
rapid diagnostics can be cost effective and have a positive impact on
antimicrobial usage is from a sexual transmitted infection clinic in London
that welcomes both male and female patients but is heavily frequented by men
who have sex with men. The clinic offers molecular testing for Chlamydia trachomatis and Neisseria gonorrhoeae using a PCR-based
method that detects the organism in urine, throat, and rectal samples from men;
and urine, throat, rectal, and vaginal swabs from women. All the specimens are self-collected and
processed on site, with results often available within 2 hours from time of
collection. Instructions for collecting
specimens are provided via short videos in specimen collection rooms. Patients enter their health information via
iPads, are instructed on which types of specimens to collect, are screened for
HIV, and receive a text message on their phone when their results are ready.
Testing volumes over the last 2 years have soared from 10,000 specimens per
annum to over 100,000, and it is estimated that they have reduced unnecessary
prescriptions for antibiotics by almost 100,000 doses, while effective therapy
has likely reduced transmission in this community.
Rapid molecular tests are also
being used in several clinical trials of novel antimicrobial agents to aid
enrollment of subjects by rapidly identifying patients with MRSA/MSSA
infections, C. difficile infections,
or in the near future, patients infected with carbapenem-resistant
Enterobacteriaceae through testing of respiratory and urine samples. In each case, the test results are available
in approximately one hour and the goal is to identify and enroll a patient in a
trial before they receive the second dose of a non-protocol antimicrobial
agent.
One challenge that remains in
many medical centers is to insure that results generated rapidly are
communicated and acted upon with equal speed by physicians. This has been a larger problem than one would
imagine. If a result is entered into the
patient’s medical record after the physician has seen the patient that day, he
or she may not look for the result until later in the day or maybe not until the
following day before rounding. To
optimize the use of rapid blood culture results, many hospitals rely on their
antibiotic stewardship program, infectious disease-trained pharmacists, or
infectious disease fellows to make sure that the result obtained influences
therapy quickly, This may mean changing vancomycin to a semisynthetic penicillin
for staphylococcal infections shown to be MSSA, or discontinuing antibiotics
for viral respiratory infections.
Given the breadth of molecular
testing options available, why is uptake of the new technologies rather slow? Many
laboratories issue newsletters letting physicians know that new rapid
technologies are being brought on line, but more than a few physicians are
reluctant to trust the new results, preferring instead to wait for traditional
test results. Ironically, the “gold
standard” susceptibility testing methods being replaced, besides being 24-48
hours slower, are often less sensitive due to outdated breakpoints. As the Infectious Diseases Society of America
indicated in its paper “Better tests, better care”, there is a considerable
educational process that is still required to bring physicians on board with
the new reality of rapid results. The
positive impact on patient management and improved outcomes of molecular
results are just beginning to be realized.
Vice President, Cepheid
904 Caribbean Drive
Sunnyvale, CA 94040
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