Is A Throat Culture Necessary In The Setting Of A Negative Rapid Streptococcal Antigen Test?
Kevin B.
Spicer,
MD, PhD, MPH
Preeti
Jaggi,
MD
Pharyngitis, or sore throat, is a common presenting complaint for acute care visits in pediatrics. Although the majority of cases of acute pharyngitis are associated with viruses, a significant percentage are related to Streptococcus pyogenes (Group A streptococcus [GAS]). Data suggest that this percentage can be in the range of 30% to 40% for children who present with acute sore throat.1 Although strep pharyngitis is a self-limited illness, suppurative (eg, peritonsillar abscess, cervical lymphadenitis) and nonsuppurative complications (eg, acute glomerulonephritis, acute rheumatic fever) can occur. A concern for these complications has led to the emphasis on treatment of acute streptococcal pharyngitis.
Because most cases of pharyngitis are related to viruses and do not require antibiotic therapy, timely and appropriate treatment of GAS pharyngitis necessitates timely and accurate diagnosis. Consequently, one of the most crucial decisions to make in evaluating a patient with pharyngitis is whether to perform a diagnostic test (eg, rapid antigen test and/or bacterial culture). The clinician needs to consider 2 principles: (1) a desire to limit the potential adverse effects to the individual associated with antibiotic treatment, and (2) a desire to limit population exposure to unnecessary antibiotics and thereby decrease the impact of antibiotic overuse as a driving force of antimicrobial resistance.
The best way to limit false-positive errors is to more appropriately test those who present with a complaint of pharyngitis. Clinical and epidemiologic characteristics can be helpful in increasing (or decreasing) the presumed likelihood of streptococcal infection, but history and examination are not sufficient for accurate diagnosis. Pharyngitis that is accompanied by rhinitis, stridor, hoarseness, conjunctivitis, cough, and/or diarrhea is highly likely to have a viral etiology; it is generally unnecessary to perform diagnostic testing for GAS when these symptoms are present. Symptoms such as an abrupt onset of fever, throat pain, headache, abdominal pain, and dysphagia, and signs such as exudative pharyngitis, palatal petechiae, uvulitis, and tender anterior cervical nodes are suggestive of GAS pharyngitis. In addition, in this context, the absence of rhinitis, hoarseness, conjunctivitis, and cough are more suggestive of GAS pharyngitis. Patients who have symptoms persisting longer than 4 to 5 days at the time of presentation are unlikely to have GAS pharyngitis, as it is a self-limited illness that usually lasts 3 to 5 days.
The traditional criterion standard for diagnosis is the throat culture (ie, culture of throat swab on sheep blood agar plate [BAP]).2 Proper collection of the throat swab specimen is of utmost importance and requires swabbing of the tonsillar tissue and the posterior pharynx. This can be problematic with the uncooperative child. The primary disadvantage of the throat culture is that it requires 24 to 48 hours and is not particularly useful for mak- ing treatment decisions during the office visit. Treatment can be withheld while awaiting culture results without increasing the risk for nonsuppurative complications, as evidence suggests that the risk for acute rheumatic fever is markedly reduced as long as treatment is initiated within 9 days of symptom onset.3 However, this may delay clinical resolution and allow for ongoing spread of disease. Consequently, rapid antigen detection tests (RADT) have been developed to more quickly identify the organism and allow prompt initiation of therapy. These rapid tests involve detection of the group-specific carbohydrate antigen from the GAS cell wall using a variety of immunologic techniques. RADTs generally have high specificity but variable sensitivity4 (Table 23-1). Sensitivity and specificity vary depending upon the population of interest, the experience and technical proficiency of the individuals obtaining the throat swabs and performing the tests, and the specifics of the gold standard throat culture (eg, office based versus laboratory based). Molecular tests for more direct detection of the organism from throat specimens have also been developed and may provide a more sensitive and specific alternative to throat culture when only the presence of GAS is of concern.5 These tests include the GASDirect Test (GenProbe, Inc, San Diego, CA), which utilizes a chemiluminescent DNA probe to detect GAS-specific rRNA sequences, and the LightCycler Strep-A assay (Roche Applied Science, Indianapolis, IN), which utilizes a real-time polymerase chain reaction (PCR) method to detect GAS-specific genetic material. These tests can provide more rapid results than culture but are not office- based assays.
Current recommendations for pediatric patients indicate that negative results on a rapid antigen test for GAS should be followed up by throat culture.2,6 Whether this is cost-effective and necessary is at least partially dependent upon the baseline rate of GAS and its complications within the population of interest. An individual or practice should evaluate the performance of their rapid test within their population to determine if this recommendation seems warranted. That is, direct comparison of the office-based RADT with culture following standard office practice (ie, office-based culture, hospital-based culture, reference laboratory–based culture) should be performed to determine the perfor- mance characteristics of the test within the typical practice of the particular clinical setting. In our own institution, a DNA probe assay (GASDirect Test) has replaced routine culture as the back-up method of GAS detection. The false-negative rate for rapid antigen testing (OSOM Strep A Test—genzyme Diagnostics, Framingham, MA) is 6% to 7% relative to the DNA probe assay (unpublished data). Because no currently available rapid test is perfect (ie, 100% sensitivity, 100% specificity) and the risk of nonsuppurative complications is higher in pediatric patients than in adults, follow-up testing of point-of-care rapid test negative specimens continues to be recommended.
Serologic testing for GAS-relevant antibodies (eg, streptolysin O, deoxyribonuclease B, hyaluronidase, and streptokinase) is not useful in acute infection because antibodies do not increase until weeks after the infection. Such testing, however, is useful in confirming recent infection, which is important in diagnosing GAS sequelae such as acute rheumatic fever and poststreptococcal glomerulonephritis.
References
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2. Bisno AL, Gerber MA, Gwaltney JM, Kaplan EL, Schwartz RH. Practice guidelines for the diagnosis and manage- ment of group A streptococcal pharyngitis. Clin Infect Dis. 2002;35(3):113-125.
3. Gerber MA, Baltimore RS, Eaton CB, et al. Prevention of rheumatic fever and diagnosis and treatment of acute streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research. Circulation. 2009;119(11):1541-1551.
4. Gerber MA, Shulman ST. Rapid diagnosis of pharyngitis caused by group A streptococci. Clin Microbiol Rev. 2004;17(3):571-580.
5. Chapin KC, Blake P, Wilson CD. Performance characteristics and utilization of rapid antigen test, DNA probe, and culture for detection of Group A streptococci in an acute care clinic. J Clin Microbiol. 2002;40(11):4207-4210.
6. American Academy of Pediatrics. Group A streptococcal infections. In: Pickering LK, ed. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:616-628. http://aapredbook.aappublications.org/cgi/content/full/2009/1/3.125. Accessed August 12, 2010.