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U.S. Department of Health and Human Services

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Use of Backup Testing for Negative Rapid Group A Strep Tests

Pharyngitis (sore throat) is caused by a number of different viruses or bacteria which set up shop in the throat and tonsil area. One of the most clinically significant bacterial organisms is group A beta-hemolytic streptococcus (GAS). Infection with GAS causes local pain and redness, bad breath, tonsillar or pharyngeal exudates and systemic symptoms like fever. Alternatively, patients may present with only mild throat pain and no fever. Anecdotal experience shows that some patients may only complain of bad breath and a history of GAS in a schoolmate or family member. [1] [2] [3]

Serious complications of GAS include rheumatic fever, rheumatic heart disease and death. Historically, treatment with intramuscular penicillin within the first several days of symptoms prevented the rheumatic complications. Because intramuscular injection of penicillin is painful this has evolved into treatment with oral penicillins. [1] [2]

While the local throat infection may clear on its own in many patients, these untreated patients are still thought to be at increased risk of rheumatic complications. Unfortunately, the literature is clear that physical examination is insufficient to accurately distinguish GAS from other causes of pharyngitis which do not present any risk of rheumatic complications. Therefore, if a patient presents with appropriate signs and symptoms a throat test for strep is performed.

The historic test of choice was throat culture. A variety of very useful non-culture based methods are available which offer quick results. These rapid tests are invaluable when they are positive for strep, but caution is required when they are negative for a variety of reasons. Pediatric practice guidelines recommend all negative rapid tests in the face of overt clinical symptoms need to be supported with follow up testing. [1] [4] [5] This is conventionally viewed as throat culture on media which is designed to augment growth of GAS, though newer methodologies may change this recommendation.[6] Notwithstanding, there is at least one study supporting clinical superiority of a rapid method compared to culture method.[7]

The situation in adults is more complex. While 15%-30% of children who present with pharyngitis have GAS, the percentage in adults may be as low as 5%-10%. [2] [3] Also, it has been reported that adults who get GAS are at a lower risk for rheumatic complications. This has been offered as a rational supporting the lack of need for confirmatory testing in adults with a negative rapid test.[8] However, there are studies suggesting that the rate of rheumatic complications in adults who present with local suppurative disease is equal to the rate in children.[3] Further, some sources quote that up to 20% of first attacks occur in middle to later life.[2]

Since no rapid test has been cleared, approved, or waived through the regulatory process as a stand alone test in the face of locally suppurative disease, lack of a backup method for a negative rapid GAS test result constitutes off label use.

While the practice of medicine is not the province of FDA regulation, regulatory medicine, like clinical medicine, is always in the process of change and FDA welcomes information from academia or industry which may contribute to the evolution of this opinion.

Bibliography:

[1]Committee on Infectious Diseases, Red Book: 2003 Report of the Committee on Infectious Diseases, 26’th Edition, Elk Grove Village IL, American Academy of Pediatrics, 2003, p 573-584.

[2]Cotran RS, Kumar V, Collins T. Robbins Pathologic Basis of Disease, 6’th Edition, Philadelphia PA, WB Saunders Company, 1999, p 572.

[3]Mandell GL, Bennett JE, Dolin R. Mandell. Douglass and Bennet’s Principles and Practice of Infectious Disease, 5’th Edition, Philadelphia PA, Churchill Livingstone, 2000, p 2119.

[4]Bisno AL, et al. Diagnosis and management of Group A Streptococcal pharyngitis: A practice guideline. Clinical Infectious Diseases. 1997; 25:574-583.

[5]Gieseker KE, et al. Comparison of two rapid Streptococcus pyogenes diagnostic tests with a rigorous culture standard. Pediatr Infect Dis J, 2002; 21:p 922-926.

[6]Gieseker KE, et al. Evaluating the American Academy of Pediatrics diagnostic standard for Streptococcus pyogenes pharyngitis: backup culture versus repeat rapid antigen testing. PEDIATRICS June 2003. 111(6): e666-e670.

[7]Uhl JR, et al. Comparison of LightCycler PCR, Rapid Antigen Immunoassay, and culture for detection of Group A Streptococci from throat swabs. J Clin Microbiol Jan 2003, 41(1): p 242-249.

[8]Bisno AL, et al. Practice guidelines for the diagnosis and management of Group A Streptococcal pharyngitis. CID 2002; 35: p 113-125.