Notes from the Field: Group A Streptococcal Pharyngitis Misdiagnoses at a Rural Urgent-Care Clinic — Wyoming, March 2015

Alexia Harrist, MD, PhD1,2; Clayton Van Houten, MS2; Stanford T. Shulman, MD3; Chris Van Beneden, MD4; Tracy Murphy, MD2

Group A Streptococcus (GAS) is the most common bacterial cause of pharyngitis, implicated in 20%–30% of pediatric and 5%–15% of adult health care visits for sore throat (1). Along with the sudden onset of throat pain, GAS pharyngitis symptoms include fever, headache, and bilateral tender cervical lymphadenopathy (1,2). Accurate diagnosis and management of GAS pharyngitis is critical for limiting antibiotic overuse and preventing rheumatic fever (2), but distinguishing between GAS and viral pharyngitis clinically is challenging (1). Guidelines for diagnosis and management of GAS pharyngitis have been published by the Infectious Diseases Society of America (IDSA)* (1). IDSA recommends that patients with sore throat be tested for GAS to distinguish between GAS and viral pharyngitis; however, IDSA emphasizes the use of selective testing based on clinical symptoms and signs to avoid identifying GAS carriers rather than acute GAS infections (1). Therefore, testing for GAS usually is not recommended for the following: patients with sore throat and accompanying symptoms (e.g., cough, rhinorrhea) that strongly suggest a viral etiology; children aged <3 years, because acute rheumatic fever is extremely rare in this age group; and asymptomatic household contacts of patients with GAS pharyngitis (1). IDSA recommends penicillin or amoxicillin as the treatment of choice based on effectiveness and narrow spectrum of activity. To date, penicillin-resistant GAS has never been documented (1).

In March 2015, a rural urgent-care clinic serving a population of 5,000–7,000 reported a substantial increase in GAS pharyngitis infections since November 2014, with some infections nonresponsive to penicillin and amoxicillin to the Wyoming Department of Health (WDH). By March 2015, the clinic reported diagnosing up to 90 cases of GAS pharyngitis per week. WDH started an investigation to verify this potential GAS pharyngitis outbreak, assess clinic testing and treatment practices, and implement control measures.

WDH reviewed a clinic-provided line list of 42 patients tested for GAS pharyngitis using rapid antigen detection tests (RADTs) during March 13–17 and two additional patients who had received diagnoses of GAS pharyngitis the previous week and returned with persistent symptoms. Patient characteristics stratified by age are provided (Table).

The line list revealed nonadherence to IDSA guidelines in testing and treatment procedures. Ten of 34 (29%) patients aged ≥3 years who were tested for GAS reported no sore throat, the symptom that should prompt evaluation for GAS pharyngitis in patients aged ≥3 years (1). Two of these 10 were asymptomatic adult contacts of patients with diagnosed GAS pharyngitis; both asymptomatic contacts had positive RADT results and were prescribed an antibiotic. Of the 24 tested patients aged ≥3 years with sore throat, 19 (79%) reported cough or rhinorrhea, symptoms that suggest a viral rather than bacterial etiology (1). Although diagnostic testing of patients aged <3 years is not routinely recommended, testing of symptomatic children who are household contacts of persons with laboratory-confirmed GAS pharyngitis can be considered (1). Among the seven patients aged <3 years who were tested for GAS pharyngitis, five (71%) had GAS-positive family members indicated by shared surname included in the line list; however, all seven (100%) had cough, and five (71%) had rhinorrhea.

Four of six patients with negative RADT results received an antibiotic. The clinic practice was to send throat swabs from patients with negative RADTs to a commercial laboratory for back-up culture, but it is unknown whether the clinic obtained any GAS-positive throat cultures from RADT-negative patients. All patients who were administered an antibiotic received a cephalosporin, clindamycin, or amoxicillin-clavulanate rather than penicillin or amoxicillin as the initial antibiotic therapy. Three patients were prescribed a second course of an antibiotic because of symptoms persisting >48 hours after the start of initial therapy; data provided did not indicate whether they were retested for GAS.

Because of the high positivity rate (38 of 44; 86%) among RADTs performed, including eight of 10 positive test results among patients aged ≥3 years without sore throat, WDH requested that the clinic perform oropharyngeal cultures on patients with positive RADTs. The clinic reported that four throat cultures collected from RADT-positive patients simultaneously with the RADT throat swab had no GAS isolated; the number of cultures submitted is unknown. Based on these results, WDH recommended that the clinic review testing procedures with the RADT manufacturer. The clinic subsequently reported to WDH that staff members were interpreting certain RADT results later than the recommended maximum incubation time of 5 minutes, a practice that can result in false-positives, according to the manufacturer.

WDH and CDC investigators reviewed IDSA guidelines for diagnosis and management of GAS pharyngitis with clinic practitioners. GAS cultured from throat swabs during subsequent weeks was confirmed to be uniformly sensitive to penicillin and amoxicillin. Subsequently, the number of RADT-positive GAS pharyngitis cases declined, and the clinic returned to using penicillin or amoxicillin as first-line therapy.

Based on the available information, investigators determined that the clinic performed RADTs on patients unlikely to have GAS pharyngitis (e.g., no sore throat, or sore throat coincident with cough or rhinorrhea), which is inconsistent with IDSA guidelines. Possible reasons for RADT-positive results among these patients are GAS carriage (1) or RADT incubation periods exceeding manufacturer recommendations. Although RADTs are highly specific (3) and allow clinicians to make treatment decisions at the time of the patient visit, incorrect technique at the point of care can result in false-positives. As a result of these errors, patients likely to have viral illness were treated with antibiotics. The patients' failure to improve led to the assumption of bacterial resistance, which prompted use of broad-spectrum antibiotics as first-line therapy in subsequent patients. The clinic practitioners' recognition of their unusually high GAS incidence, request for assistance, and compliance with suggested interventions were critical in identifying and amending problematic practices.

Sore throat is one of the most common symptoms reported by outpatients (4,5), with viral infections responsible for the majority of cases (1). Correct diagnosis and treatment of GAS pharyngitis prevents acute rheumatic fever, shortens illness duration, and reduces person-to-person spread (2); however, antibiotic overuse for sore throat is common among both children and adults (4,5). This can result in unnecessary side effects and promote development of antibiotic resistance. Clinics should take steps to ensure practitioner understanding of and adherence to published guidelines, and to promote the use of good laboratory practices, such as periodic evaluation of competency in testing procedures (6).

1Epidemic Intelligence Service, CDC; 2Public Health Sciences Section, Wyoming Department of Health; 3Division of Infectious Diseases, Ann & Robert H. Lurie Children's Hospital, Northwestern University School of Medicine, Chicago, Illinois; 4Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, CDC.

Corresponding author: Alexia Harrist, alexia.harrist@wyo.gov, 307-777-5532.

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