Reflexive Culture in Adolescents and Adults With Group A Streptococcal Pharyngitis

MAJOR ARTICLE Reflexive Culture in Adolescents and Adults With Group A Streptococcal Pharyngitis Tanis C. Dingle,1 April N. Abbott,1 and Ferric C. Fang1,2,3 Departments of 1Laboratory Medicine, 2Microbiology, and 3Medicine, University of Washington, Seattle Background. Guidelines currently provide conflicting recommendations regarding the diagnosis of group A streptococcal (GAS) pharyngitis in adults. Clinical guidelines state that negative rapid antigen detection tests (RADTs) do not require confirmation by a backup method in adults, whereas laboratory-based guidelines mandate confirmation of a negative RADT in patients of all ages. The objective of this study was to assess the utility of reflexive culture following a negative RADT in adolescents and adults with suspected GAS pharyngitis. Methods. A retrospective analysis of 726 patients, aged ≥13 years, with negative RADTs and positive GAS throat cultures, was performed between 1 January 2000 and 31 December 2011 at 2 academic medical centers in Seattle, Washington. Complication rates, treatment, modified Centor score, and bacterial burden in patients with negative RADTs and positive GAS throat cultures were assessed. Results. Modified Centor scores ≥2 were observed in 55% of patients with a negative RADT and positive GAS culture. Of these, 77% of patients had a moderate or heavy bacterial burden (≥2+). RADTs failed to detect some patients who presented with serious complications of GAS pharyngitis: 29 (4.0%) had peritonsillar abscesses and 2 (0.28%) were diagnosed with acute rheumatic fever. Providers found culture results to be useful for initiating antibiotic therapy or confirming a clinical diagnosis. Antibiotic treatment was prescribed in 68.7% of patients, with culture-directed initiation of therapy documented in 43.5%. Conclusions. Reflexive GAS culture is clinically useful when RADTs are negative. RADTs fail to detect a substantial number of adult patients with clinically significant pharyngitis who can benefit from treatment. Keywords. group A streptococcus; pharyngitis; rapid antigen detection test; strep throat. Sore throat is one of the most common complaints encountered in the outpatient setting [1]. Bacteria are responsible for 5%–15% of acute pharyngitis, with group A streptococci (GAS; Streptococcus pyogenes) the most common etiology [2]. Not all patients with GAS pharyngitis require treatment. Mild GAS pharyngitis is generally self-limited, and significant nonsuppurative sequelae (eg, rheumatic fever and poststreptococcal glomerulonephritis) are rare in adults. In addition, some believe that treatment of pharyngitis contributes to Received 23 March 2014; accepted 17 May 2014; electronically published 27 May 2014. Correspondence: Ferric C. Fang, MD, Department of Laboratory Medicine, University of Washington School of Medicine, 1959 NE Pacific St, Box 357110, Seattle, WA 98195-7110 (). Clinical Infectious Diseases 2014;59(5):643–50 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: . DOI: 10.1093/cid/ciu400 the problem of antibiotic overuse [3]. However, studies indicate that antimicrobial therapy can prevent complications, decrease infectivity, and ameliorate symptoms, particularly in individuals with severe symptoms [4–6]. Thus, an accurate diagnosis of GAS pharyngitis in the appropriate clinical setting can identify patients in whom therapy is beneficial. GAS pharyngitis symptoms overlap with other respiratory infections, making clinical diagnosis unreliable. Four characteristics termed the Centor criteria aid clinicians in predicting the probability of GAS pharyngitis [7]: tender anterior cervical lymphadenopathy, history of fever (>38°C), tonsillar exudate, and absence of cough. These criteria, developed >30 years ago, have since been validated as a decision-making tool across a variety of settings and remain in use today [8, 9]. A modified version, the McIsaac score [10], adjusts the Centor score based on patient age and performs similarly to the Centor score [9]. The gold standard for Reflexive Culture in Streptococcal Pharyngitis • CID 2014:59 (1 September) • 643 the diagnosis of GAS in the clinical laboratory is throat swab culture, but performance is dependent on appropriate collection and culture techniques to achieve >90% sensitivity [11, 12]. Culture has the added advantage of identifying other causes of acute bacterial pharyngitis, such as group C and group G streptococci and Arcanobacterium haemolyticum, but requires a longer turnaround time (24–48 hours). GAS-specific RADTs provide rapid results but sensitivity is only 55%–85% [13, 14]. Several guidelines for the diagnosis and treatment of GAS pharyngitis in adults have been published. However, current diagnostic recommendations are conflicting [3, 15]. The Infectious Diseases Society of America (IDSA) guidelines recommend performing an RADT on adults clinically and epidemiologically suspected to have GAS pharyngitis, with negative results sufficient to exclude the diagnosis [11]. This recommendation is based on the lower prevalence of GAS pharyngitis in adults compared with children, and the rarity of rheumatic fever in industrialized countries [11]. The American College of Physicians–American Society of Internal Medicine (ACP-ASIM) guidelines use clinical criteria to identify patients for whom testing is indicated [16, 17]. No testing is recommended for patients with Centor scores of 0 or 1. For scores of 2 or 3, microbiologic confirmation is recommended. Patients with a positive result are treated with antibiotics, and those with a negative result receive conservative care. For patients with Centor scores of 4, antibiotics are recommended with or without laboratory confirmation [16, 17]. Reflexive culture in adults following negative RADT is not recommended by the ACP-ASIM. The latter guidelines have been endorsed by the Centers for Disease Control and Prevention (CDC), provided that the local RADT sensitivity is 80% [18]. The ACP-ASIM also endorses an alternative strategy of empiric treatment of individuals with Centor scores of 3 or 4, without laboratory testing in patients with lower Centor scores [16, 17]. Other US guidelines (American Heart Association, Institute for Clinical System Improvement) continue to recommend reflexive throat culture in adults with negative RADTs [15]. Despite the IDSA and ACP-ASIM recommendations, many clinical microbiology laboratories in the United States continue to perform throat cultures in patients with negative RADTs. Confirmation of a negative RADT with another method is required by the College of American Pathologists, Joint Commission [19] ( pending review of RADT sensitivity) and the US Food and Drug Administration (FDA) [20]. According to the FDA, performance of an RADT without a backup method constitutes off-label use [20]. The clear disagreement between US clinical and laboratory guidelin (...truncated)