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MICROBIOLOGY Clinical Microbiology
Point-Counterpoint: A Nucleic Acid Amplification Test for
Streptococcus pyogenes Should Replace Antigen Detection and Culture
for Detection of Bacterial Pharyngitis
Bobbi S. Pritt, Robin Patel, Thomas J. Kirn, Richard B. Thomson, Jr.C.d
Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA, Departments of Pathology & Laboratory
Medicine and Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA, Department of Pathology & Laboratory Medicine, North Shore
University Health System, Evanston, Illinois, USAS; The University of Chicago Pritzker School of Medicine, Chicago, Illinois, USA
Nucleic acid amplification tests (NAATs) have frequently been the standard diagnostic approach when specific infectious agents
are sought in a clinic specimen. They can be applied for specific agents such as S. pyogenes, or commercial multiplex NAATs for
detection of a variety of pathogens in gastrointestinal, bloodstream, and respiratory infections may be used. NAATs are both
rapid and sensitive. For many years, S. pyogenes testing algorithms used a rapid and specific group A streptococcal antigen test
to screen throat specimens, followed, in some clinical settings, by a throat culture for S. pyogenes to increase the sensitivity of its
detection. Now S. pyogenes NAATs are being used with increasing frequency. Given their accuracy, rapidity, and ease of use,
should they replace antigen detection and culture for the detection of bacterial pharyngitis? Bobbi Pritt and Robin Patel of the
Mayo Clinic, where S. pyogenes NAATs have been used for well over a decade with great success, will explain the advantages of
this approach, while Richard (Tom) Thomson and Tom Kirn of the NorthShore University HealthSystem will discuss their con-
cerns about this approach to diagnosing bacterial pharyngitis.
A Charyngitis cig
. Whicorunarepe
, snobiet or the prediction Galles
POINT
clinicians to apply various clinical prediction rules, such as the
cute pharyngitis is one of the most common diagnoses made Centor criteria, which attempt to differentiate viral from GAS
for the majority of cases, Streptococcus pyogenes (beta-hemolytic have demonstrated acceptable sensitivity for justifying the elimi-
group A streptococci (GAS]) and, less commonly, other bacteria nation of laboratory testing (5, 8, 9). Methods for laboratory de-
are estimated to cause 25% of the cases in adults and nearly 40% of tection of S. pyogenes include rapid antigen detection tests
the cases in children (2–4). Most cas of GAS haryngitis are (RADTS), bacterial culture, and nucleic acid amplification tests
mild and self-limited, although potential complications in- (NAATS). RADTs are commercially available and widely used for
clude peritonsillar abscesses, otitis media, mastoiditis, cervical detection of S. pyogenes in point-of-care settings because of their
lymphadenitis, pneumonia, rheumatic fever, and poststrepto- ease of use, low cost, and ability to produce results rapidly. They
coccal glomerulonephritis. Antimicrobial therapy may prevent generally exhibit high specificity for detection of S. pyogenes, and
these complications and may also shorten the duration of illness thus, positive results do not need to be routinely confirmed by
and potentially minimize the spread of infection to others; for another method. However, RADTs have relatively low sensitivity,
these reasons, antibiotics are frequently administered, particularly with most reported levels ranging from 70 to 90% (10, 11). Fur-
to children and to adults with severe GAS pharyngitis (5,6). ther, test sensitivity is dependent on the severity of disease, with
We acknowledge that implicit in any diagnostic strategy is an poorer sensitivity (47 to 65%) in patients with lower modified
assumption that results will be actionable, which, in the case of Centor scores (12). For these reasons, it is common practice to
GAS pharyngitis, means that treatment would be administered. confirm negative RADT results with bacterial culture. National
We realize that GAS pharyngitis, especially when it is nonsevere, is and European guidelines provide guidance for performing confir-
not universally treated and that there are geographic practice dif- matory testing but differ in their recommendations (13). The In-
ferences. There are a number of reasons for this, including that fectious Diseases Society of America and the American Heart As-
antibiotics have a relatively small effect in reducing symptoms and
symptom duration, that rheumatic fever and poststreptococcal
glomerulonephritis are rare in certain populations, that antibiot- Accepted manuscript posted online 20 July 2016
ics risk disturbing the microbiome (and consequently increasing Citation Pritt BS, Patel R. Kirn TJ, Thomson RB, Jr. 2016. Point-Counterpoint: A
the risk of conditions such as thrush and Clostridium difficile-
nucleic acid amplification test for Streptococcus pyogenes should replace antigen
detection and culture for detection of bacterial pharyngitis. J Clin Microbiol
associated diarrhea), that antimicrobial use may result in allergies
542413-2419. doi:10.1128/JCM.01472-16.
and other adverse drug effects, and also because of the associated
Editor: P.H.Gilligan, UNC Health Care System
cost and logistics of testing and treatment. Despite these contro-
Address correspondence to Robin Patel, patel.robin@mayo.edu, or
versies, which we will subsequently propose justify an outcome- Richard B. Thomson, Jr., RThomson@northshore.org.
based, cost-effectiveness study using modern diagnostics, we as-
Copyright © 2016, American Society for Microbiology. All Rights Reserved.
sume herein that making a diagnosis of GAS is generally desired
The views expressed in this feature do not necessarily represent the views of the journal
and that therefore the ideal way to do so should be used.
or of ASM.
A seemingly straightforward way to guide antibiotic use is for
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October 2016 Volume 54 Number 10
Journal of Clinical Microbiology
jem.asm.org 2413
S. pyogenes NAAT for Bacterial Pharyngitis Detection
LOUTPATIENT
B
sociation recommend performing bacterial cultures for children
and adolescents with negative RADT results but do not recom-
mend reflex cultures for adults with negative RADT results, given
the lower incidence of S. pyogenes pharyngitis and rheumatic fever
in this population (5, 14). However, new evidence suggests that
reflexive culture may be indicated for adults, as well as children
and adolescents, since RADTs fail to detect GAS pharyngitis in a
significant number of adults (13). Some groups, such as the Amer-
ican College of Physicians and the American Society of Internal
Medicine, use clinical (Centor) criteria rather than patient age to
guide testing (15, 16). Given the conflicting information, many
clinical microbiology laboratories opt to perform culture on all
patients with negative RADTs. Culture confirmation of negative
results is also required by the United States Food and Drug Ad-
ministration for some RADTS.
Beyond culture being considered the gold standard for the di-
agnosis of GAS pharyngitis, it can be used to detect other causes of
Downloaded from
Point-Counterpoint
yngitis should be routinely pursued is an open question. For ex- clinical practice. Finally, future tests for GAS pharyngitis may
ample, a study of the effect of antibiotic treatment on the outcome need to assess macrolide susceptibility, given that not all GAS
of pharyngitis associated with detection of F. necrophorum in an strains are macrolide susceptible and that macrolides may be
associated throat swab could be considered (19, 20).
prescribed to penicillin-allergic patients with GAS pharyngitis.
What is new for S. pyogenes NAATs? The advent of Clinical
Bobbi S. Pritt and Robin Patel
Laboratory Improvement Amendments (CLIA)-waived rapid
NAATs for S. pyogenes detection, such as the Roche Cobas Liat and ACKNOWLEDGMENTS
the i Strep A (Alere, Waltham, MA) (21, 22), provides new oppor-
tunities for the rapid diagnosis of GAS pharyngitis. These NAATS
R.P. reports grants from BioFire, Check-Points, Curetis, 3M, Merck,
Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, Allergan,
as easily and quickly performed as RADTs. We recently com-
and The Medicines Company. R.P. is a consultant to Curetis, Roche,
pared the performance of the Cobas Liat Strep A assay with our
Qvella, and Diaxonhit; monies are paid to the Mayo Clinic. In addition,
PCR assay by using residual material from 200 throat swabs that
R.P. has a patent on a Bordetella pertussis/B. para pertussis PCR assay is-
were submitted for S. pyogenes testing and showed the two assays sued, a patent on a device/method for sonication, with royalties paid by
to have equivalent performance characteristics (21). Of the 200 Samsung to the Mayo Clinic, and a patent on an antibiofilm substance
specimens tested, 114 were negative and 84 were positive by both issued. R.P. serves on an Actelion data monitoring board, receives travel
assays. The remaining two specimens were positive only with the reimbursement and an editor's stipend from ASM and IDSA, and receives
Liat assay but had originally tested positive by our PCR assay.
honoraria from the USMLE, Up-to-Date, and the Infectious Diseases
These assays take
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