Use of a High-Sensitivity Rapid Strep Test Without Culture Confirmation of Negative Results

ICD-9 codes identified one patient with a principal diagnosis of poststreptococcal glomerulonephritis in period 2.

Discussion

Rapid accurate diagnosis of pharyngeal infections attributable to GABHS can be difficult. Diagnosis based on clinical signs and symptoms alone is often inaccurate. Although BAP throat culture is widely held as the gold standard of diagnosis, the sensitivity of this method varies from 75% to 98% when compared with a more rigorous gold standard, such as Todd-Hewitt broth culture.^17,18 Reasons for the variable performance of BAP cultures include the absence of a universally accepted procedure and variability in the number and type of collection swabs, the type of culture media used, the duration of incubation, the atmosphere of incubation, and the specific Lancefield grouping procedure used.²⁰ Also, because throat cultures require 24 to 48 hours to achieve a definitive result, their use may lead to incomplete follow-up, missed opportunity to treat those infected, increased morbidity, delayed return to normal activities for both child and caretaker, and increased spread of disease.¹⁸

During the 1980s a number of antigen detection tests for GABHS became available, with most of these tests relying on latex agglutination or membrane-based immunoassay techniques. The advantages of these tests were rapid diagnosis and initiation of therapy. The main disadvantage was their sensitivity, which has been demonstrated to be as low as 50% and 70% with the latex agglutination tests14 and 70% to 90% with the more recently developed immunoassay tests.^15-18 Because of their historically low sensitivity, the American Academy of Pediatrics (AAP) and the American Heart Association (AHA) have always recommended that a confirmatory culture should be obtained for antigen test–negative patients suspected of having GABHS pharyngitis.^12,13

Policies advocating routine culture confirmation have been challenged.^17,18 Although the AAP and AHA concerns are well-grounded in theory, there have been no outcomes studies that have examined pharyngitis complication rates in detail. Despite the widespread use of antigen tests without culture confirmation of negative results,²¹ we have not witnessed a rise in the all-time low rates of acute rheumatic fever currently being seen in this country.²² Although there have been several local epidemics of acute rheumatic fever reported in this country during the past 2 decades,^23,24 falsely negative antigen tests have not been mentioned as a contributing factor for any of them.

Limitations

This is the first clinical outcomes study in which complication rates following use of a high-sensitivity antigen test without culture confirmation of negative results was assessed. Our study has many limitations. Because it is a retrospective case series, we cannot definitively dismiss the possibility that there was a change in the virulence of the GABHS strains encountered during the 4 years studied, although there was no change in the rates of invasive GABHS seen in the clinical microbiology laboratory at the Lahey Clinic during each of the periods studied.

Although chart review revealed the ICD-9 and CPT codes used to be accurate, we also cannot dismiss the possibility that some codes other than those specified were used to document complications of pharyngitis, such that those cases could not be included in our analysis. In an effort to maximize patient inclusion before beginning this study, we reviewed all potential CPT and ICD-9 codes with coding personnel and subsequently used all those codes in our analysis. We also included all patients with either a primary or secondary diagnosis code matching one of the ICD-9 codes selected.

Despite these flaws, this study is important because it illustrates a number of important facts about the management of pharyngitis in the current era. First, acute rheumatic fever is a rare disease in this country. During the 4 years of this study, there were more than 2 million outpatient visits to the Lahey Clinic and more than 30,000 visits for pharyngitis. There were no new or recurrent cases of acute rheumatic fever seen at the clinic during the 4 years studied. Moreover, during the first 5 years of this decade there was only one case of acute rheumatic fever from the entire Commonwealth of Massachusetts reported to the Centers for Disease Control and Prevention.²² Because of its low incidence, the absence of acute rheumatic fever we found in our study may have been due to chance alone and not to a change in diagnostic strategy used. Although this may be the case, it does not seem to be logical or cost-effective to recommend routine culture confirmation of all negative antigen tests unless a local epidemic of acute rheumatic fever warrants such a strategy.

Second, although there was one case of poststreptococcal glomerulonephritis during period 2, antibiotics are of little or doubtful benefit in preventing this complication.^25,26 Because diagnosis and therapy have little, if any, impact on the development of this complication, culture confirmation of negative antigen tests in an effort to prevent this rare complication cannot be justified.