Background:The role of non-group A streptococci (non-GAS) as pathogens of acute pharyngitis is controversial. Data are limited and conflicting on whether these bacteria are true pathogens of pharyngitis and whether treatment is indicated in all cases or just select cases. However, non-GAS are well-documented as being pathogens of other diseases, including neonatal sepsis, pneumonia, endocarditis, and urinary tract infections. If non-GAS are pathogens of acute pharyngitis, treatment may speed recovery as well as prevent complications. The objective of this study was to determine whether, in cases of pharyngitis in which non-GAS is identified on culture, the clinical signs and symptoms resemble those of group A streptococcal pharyngitis thus implicating them as true pathogens or if they resemble culture-negative pharyngitis, suggesting these cases are viral in etiology.Method: This was a 3-group retrospective case-control study (N ‫؍‬ 915; mean age, 26 years). Cases included all patients with non-GAS identified on culture (n ‫؍‬ 180). The control group 1 consisted of all patients with GAS infection identified by a rapid strep test or culture (n ‫؍‬ 145); control group 2 included all patients with a negative rapid strep test and culture (presumed viral pharyngitis; n ‫؍‬ 584). Multivariate analysis was used to compare the prevalence of 5 clinical features among the groups.Results: The presence of headache and fever was significantly associated with streptococcal infection, with no difference between GAS and non-GAS infection. Exudates and lymphadenopathy were also significantly associated with both GAS and non-GAS infection compared with viral infection. When 2 criteria were present, the risk of any streptococcal infection rose to 55% (27% for non-GAS or GAS); when 3 or more criteria were present, the rate of any streptococcal infection rose to 81% (non-GAS infection, 34%; GAS infection, 47%).Conclusion: In this predominantly young, adult population with acute pharyngitis, non-GAS infection was as common as GAS infection and was associated with the same clinical features typically associated with GAS. Although the benefits of treating non-GAS pharyngitis in terms of either symptomatic relief or prevention of sequelae are unproven, clinicians may want to consider treating patients with proven or presumptive non-GAS pharyngitis who fail to respond to symptomatic therapy or who are at increased risk for sequelae of group B or group C streptococcal infections, such as those patients who are or have close contact with pregnant women, neonates, and elderly or immunocompromised persons. Further study is needed to determine whether patients with non-GAS pharyngitis benefit from targeted antibiotic treatment. (J Am Board Fam Med 2009;22:663-669.)