Abstract
Acute pharyngitis in adults is primarily a viral infection; only about 10% of cases are of bacterial etiology. Most cases of bacterial pharyngitis are caused by group A beta-hemolytic streptococci (GABHS). One laboratory method for the diagnosis of GABHS is rapid antigen diagnostic testing (RADT), which can be processed during an emergency department visit and which has become a popular alternative to throat swab cultures. We conducted a study to define the sensitivity and specificity of RADT, using throat culture results as the gold standard, in 100 emergency department patients who presented with symptoms consistent with streptococcal pharyngitis. We found that RADT had a sensitivity of 68.2% (15 of 22), a specificity of 89.7% (70 of 78), a positive predictive value of 65.2% (15 of 23), and a negative predictive value of 90.9% (70 of 77). We conclude that RADT is useful in the emergency department when the clinical suspicion is GABHS, but results should be confirmed with a throat culture in patients whose RADT results are negative.
Introduction
Acute pharyngitis accounts for 1 to 2% of all visits to primary care physicians. 1 In adults, its etiology is primarily viral; only about 10% of cases have a bacterial cause, most commonly group A beta-hemolytic streptococci (GABHS). 2 Among children and adolescents, GABHS affects between 15 and 30% of those with pharyngitis. 3
The Infectious Diseases Society of America, the American Heart Association, and the American Academy of Pediatrics recommend antibiotic treatment of acute pharyngitis only for those patients with positive GABHS cultures. 4 Therefore, when a clinician evaluates a patient with an acute sore throat, the most important clinical task is to decide whether the patient has “strep throat.” 2 In view of the variability in clinical presentations of GABHS pharyngitis and the large number of other infectious agents that are capable of producing similar signs and symptoms, a clinical diagnosis of GABHS pharyngitis is unreliable. 5 Physicians must use a laboratory test to ascertain the diagnosis. Recovery of GABHS from throat swab cultures has been regarded as the standard criterion for the diagnosis of GABHS pharyngitis, even though this technique does not distinguish between colonization and acute infection. Moreover, the results of throat swab cultures do not become available for 24 to 48 hours. Therefore, a more precise and rapid method of diagnosing GABHS pharyngitis is desirable.
We investigated one such option, rapid antigen diagnostic testing (RADT), which can be processed during an office or emergency department visit and which has become a popular alternative to throat swab cultures. 6 The goal of our study was to define the sensitivity and specificity of RADT, using culture results as the gold standard, in patients who presented with symptoms of acute streptococcal pharyngitis.
Patients and methods
Our study population was made up of 100 consecutively presenting patients—63 women and 37 men, aged 18 to 64 years (mean: 31.14 ± 7.93)—who had been diagnosed in our institution's Emergency Department with acute pharyngitis according to Centor criteria. 7 The Centor criteria were developed to estimate the probability of acute GABHS pharyngitis in newly presenting patients. This model takes into consideration four clinical features: (1) a history of fever, (2) an absence of cough, (3) the presence of pharyngeal or tonsillar exudates, and (4) the presence of tender anterior cervical lymphadenopathy. Emergency physicians obtained two swabs simultaneously from each patient—one from the tonsils and one from the posterior wall of the oropharynx.
RADT
For rapid antigen detection, we used the Quick-Vue+ Strep A Test (Quidel Corp.; San Diego). With this test, antigen is extracted from the swab specimen with reagents A and B. If the sample contains strep A antigen, a vertical pink line appears superimposed over a printed horizontal blue line to form a plus sign in the READ RESULT window, indicating a positive result. If strep A is not present in the sample, the READ RESULT window shows only the printed blue horizontal line, which represents a minus sign to indicate a negative result.
Culture and identification
For the throat cultures, we cultivated specimens in Bacit-A culture medium (Salubris; Cambridge, Mass.). Bacit-A comes as a ready-to-use medium in a two-section plate. One section contains sheep blood agar and the other section contains sheep blood agar with bacitracin. Throat samples are streaked onto both sections, first on the side without bacitracin and then on the side with it. The plate is incubated overnight at 37°C. The presence of beta-hemolytic colonies on the side without the bacitracin and their absence on the side with the bacitracin indicates the presence of GABHS. The throat culture results served as our gold standard, and we used them as the basis for evaluating the reliability of the RADT results.
Statistical analysis
Our primary study parameters were RADT's sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
Results
Culture was positive in 22% of patients and negative in 78%. RADT was positive in 23% and negative in 77%. Some 85% of our patients had the same result on both culture and RADT; among the others, 8% showed only antigen positivity and 7% showed only culture positivity. Therefore, the sensitivity of RADT was 68.2% (15 of 22), the specificity was 89.7% (70 of 78), the PPV was 65.2% (15 of 23), and the NPV was 90.9% (70 of 77).
Discussion
In a review of published studies, Gerber and Shulman reported that the sensitivity of RADT for GABHS when evaluated against standard throat culture ranged between 70 and 90%. 8 A lower figure was reported by Lieu et al, who studied 255 children who presented to a busy urban emergency department with acute pharyngitis and who were simultaneously tested with RADT and a throat culture. 9 They found RADT had a sensitivity of only 55% compared with throat culture. Needham et al performed an investigation to determine if the availability of RADT results in patients with acute GABHS pharyngitis improved their care (it did). 10 In that study, the sensitivity and specificity of RADT were 87 and 97%, respectively. We found the sensitivity and specificity RADT to be 68.2 and 89.7%, respectively.
The sensitivity of RADT may be related to the size of the GABHS inocula present on the throat swabs. Theoretically, several different mechanisms could lead to variations in throat swab inocula. The technique of the clinicians who obtain throat swabs must be adequate and uniform in pharyngitis patients. Otherwise, pharyngitis might be missed in those patients who have few colonies of GABHS in their pharynx. 6
In our study, the 90.9% NPV of RADT alerts us to the fact that 9% of patients with negative tests had positive cultures. As pointed out by Neuner and colleagues, the risk of preventable severe suppurative or nonsuppurative complications in adults with GABHS pharyngitis is small. 11 Since RADT has a high NPV, antibiotic use could be postponed. However, the Infectious Diseases Society of America, the American Heart Association, and the American Academy of Pediatrics recommend that all negative RADT results be confirmed by a throat culture. 4
In our study, the PPV of RADT was 65.2%. The PPV is important to know because it affects the decision to start antibiotic therapy. If a RADT result is positive, there is no need to wait for a culture result before starting antibiotic therapy.
In conclusion, the results of RADT in different clinical studies have been variable. These variations may be attributable to technical factors and/or nonspecific diagnostic criteria. A negative RADT result should be verified by a standard throat culture, and antibiotic therapy can be delayed until after the results of the culture are known. When a RADT result is positive, antibiotic therapy should be started, which may prevent the complications of GABHS disease. RADT is beneficial in the emergency department when the clinical suspicion is GABHS, provided that standard throat culture is available for patients whose RADT results are negative.