Sore throat is a common reason that patients consult with a physician. Most of these are viral infections related to upper respiratory infections, but about 20% are secondary to infection with Group A P-hemolytic streptococcus. The primary role of the physician is to differentiate streptococcal pharyngitis from viral illnesses. Despite the fact that most sore throats are due to viruses, often patients receive antibiotics for this condition even when streptococcal illness is not likely to be present (62). This leads to selection of resistant organisms as well as reinforcement of the desire for antibiotics on the part of the patient (63).
Because most patients with sore throats probably do not visit their doctor, it is difficult to state with any certainty how often sore throats occur in healthy populations. However, pharyngitis ranked fourth in the most common reasons for visits to family physicians in two different studies (64,65). Frequently antibiotics are prescribed for these conditions without evidence of a bacterial etiology.
Both viral and Group A streptococcal pharyngitis have peak occurrences in the winter and early spring. Streptococcal infection, in particular, can be recognized in epidemic patterns frequently affecting groups that spend considerable time together in close quarters, such as day cares, schools, and places of employment. Strep throat also is related to patient age. While infection in the very young (< 1 yr old) is uncommon, the peak occurrence for strep throat is between 3 yr and 10 yr of age with diminished risk over the age of 20.
The most common causes of pharyngitis are respiratory viruses. Adenovirus and the rhinoviruses account for approx 80% of cases of sore throat in children seen by physician (66,67). Coxsackievirus, herpesvirus, and Epstein-Barr virus can cause tonsillitis, but are less common than adenovirus (68). Adenovirus, coxackievirus, and Epstein-Barr can cause exudative pharyngitis that can mimic the appearance of strep-tococcal infection. Although exudative tonsillitis is thought to be a hallmark of group A streptococcal infection, this sign is actually present more often from adenovirus than from streptococcus.
Group A P-hemolytic streptococcus can cause an acute tonsillopharyngitis, but may colonize the oropharynx without symptoms. The asymptomatic carrier rate of Group A streptococcus ranges from approx 10% to 30% of healthy children, a rate that nearly matches the true infection rate (69,70). This means that in testing for group A streptococcus, positive tests are just as likely to occur from carriers of Group A streptococcus who have a concomitant virus as those actually infected with the organism. In contract to Group A streptococcal tonsillopharyngitis, treatment of the carrier state is not necessary and does not reduce symptoms or complications (71).
Another dilemma in identifying Group A streptococcus in patients with pharyngitis is the sensitivity of rapid group A antibody kits compared to a throat culture. Many studies have shown that a rapid test is less sensitive than the culture for identifying the presence of Group A streptococcus. Sensitivities for the rapid test compared to a standard blood agar culture vary considerably but are generally in the range of 60-70%. Studies also have demonstrated that in circumstances when the colony counts are low, rapid tests are more likely to miss the presence of Group A streptococcus. However, when the sero conversion of anti-streptolysin-O (ASO) titers is used as the gold standard for infection, rapid tests perform very well (72). It is likely that rapid tests miss patients who have a small number of organisms but who are likely to be colonized rather than infected. Thus, rapid testing may be more specific in identifying patients with actual streptococcus related disease than cultures that also identify those who are likely to be carriers. This suggests that follow-up throat cultures are not necessary and may actually confuse treatment decisions. Rapid streptococcus testing without culture also has been shown to be the most cost-effective approach to managing acute pharyngitis (73).
As indicated previously, reports regarding the role of Chlamydia and Mycoplasma indicate that these two organisms also may be associated with acute pharyngitis. However, there have been few treatment trials that demonstrate any benefit of treating non-Group A streptococcus with antibiotics that would treat either of these organisms. In a study using erythromycin to treat non-Group A streptococcal pharyngitis (74), patients who received placebo had the same speed of symptom resolution as those treated with active antibiotics.
Group A p-Hemolytic Streptococcal Tonsillopharyngitis
Differentiating Group A streptococcal pharyngitis from viral disease is the most vexing problem in the management of acute sore throat. The clinical impression of the treating physician has been shown to be fairly inaccurate at making this differentiation (72,75,76). Several clinical decision rules have been evaluated to assist physicians in selecting patients for testing or treatment. One simple system that relied on the presence of fever, lymphadenopathy, exudative tonsillitis, and the absence of a cough improved the positive predictive value of a rapid Group A test significantly (72). Another study using expanded clinical criteria noted that unnecessary antibiotic prescribing would have been reduced 48% had a decision rule that looked at a wide variety of predictors been used to guide therapy (75).
Once Group A streptococcus has been implicated in the infection, the choice of antibiotic is controversial. With only scant evidence that treatment reduces the symptomatic period and a low risk of complications from untreated Group A streptococcal pharyngitis, some investigators suggest that antibiotic treatment carries more risks than not treating and encourages future health seeking and antibiotic expectations for future sore throats (77). However, formal decision analyses suggest that in cases of moderate probability of strep throat (40-85%) with symptom duration of 2 d or less, rapid streptococcus testing and treatment is beneficial (78).
Selection of an appropriate antibiotic and duration of therapy are important considerations in treating streptococcal pharyngitis. Penicillin V resistance in Group A strep tococcus as well as erythromycin resistance (79) has led to investigations of other drugs for management of strep throat. Because streptococcal pharyngitis is a self-limited problem even without antibiotic therapy, much of this resistance has been based on positive throat cultures following the termination of treatment. This may be misleading, as colonized patients may continue to harbor streptococcus even after therapy.
When drug failure rates are examined with penicillin, cultures remain positive in 11-45% of treated patients (80,81). However, single-dose therapy with amoxicillin at 40 mg/kg/d for 10 d appears to be very successful, resulting in excellent clinical responses and low rates (5-10%) of posttreatment carrier rates (80,81). Treatment with other agents such as azithromycin and clarithromycin produces no better results than amoxicillin or penicillin V (82-84), but at much greater expense.
Attempts at "short-course" therapy have been studied with azithromycin (85). Both short-course treatment with azithromycin and 10 d of cefaclor have exactly the same clinical cure rates (86%) by d 3 of therapy. However, patients treated with cefaclor were less likely to become recolonized with Group A streptococcus over the next 45 d than those treated with the short course of azithromycin (20% vs. 55%). As the significance of rapid recolonization is still unclear, short-course therapy with azithromycin or other antibiotics still requires additional investigation.
While the carrier rate does not require treatment (71), some clinicians attempt to eradicate those colonized by Group A streptococcus to prevent spread to other family members and close contacts. A regimen of intramuscular penicillin V plus oral rifampin has been shown to reverse the carrier status in 93% of patients treated (86). There have been no studies performed more recently that have explored whether this regimen remains effective with increased Group A streptococcus resistance to penicillin.
Despite evidence that Chlamydia and Mycoplasma may be associated with acute pharyngitis, there have been no studies that have shown a benefit from treatment of patients with non-Group A streptococcal pharyngitis with antibiotics. Studies with penicillin (72), which would not be expected to cover these agents, and macrolides (74), which would, have not shown any significant improvement over placebo. Until specific tests that can rapidly identify these organisms are developed that would allow for targeted treatment and studies can demonstrate that treatment reduces symptoms and complications, indiscriminate antibiotic therapy for non-Group A streptococcal pharyngitis should be avoided.
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