Sore throat is a common complaint in the emergency department and outpatient clinic setting. “Strep throat” caused by Streptococcus pyogenes accounts for just 5%-15% of all adult pharyngitis and tonsillitis. Most cases are caused by viruses, yet more than 75% of adult patients receive antibiotics. Why do we prescribe antibiotics? The answers are many:¹

• It is clinically difficult to determine who actually has pharyngitis caused by S. pyogenes.
• Testing takes time and is expensive.
• If only culture is available, there can be no point-of-service answer.
• Explaining to uninformed patients why antibiotics are indicated only in certain situations is time-consuming and can be frustrating.
• Medical-legal concerns (rheumatic fever and suppurative complications, such as peritonsillar abscess) may be a factor.
• Patients expect and “demand” antibiotics (customer satisfaction concerns).

Overall, it may be easier to just write the prescription! Let’s pose some simple questions about “sore throats” and get some (hopefully) simple answers on effective diagnosis and management.

Which Patients Get “Strep Throat”?

Most cases (40%-60%) of pharyngitis are caused by viral infections, with the remainder caused by other bacterial infections, fungal infections, or irritants (pollutants or chemicals).² Group A beta-hemolytic streptococcus (GABHS) pharyngitis is more common in children and adolescents between 5 and 15 years old, especially during the late autumn, winter, and early spring months in temperate climates (20%-30%). Adults have a much lower prevalence of GABHS infection (5%-15%).

The most common bacterial etiology of pharyngitis is GABHS. Other less-frequent isolates include group C and G strep, Fusobacterium necrophorum,³ Neisseria gonorrhoea, Corynebacterium diphtheriae (diphtheria), Mycoplasma pneumoniae, and several chlamydial species.^4,5

Viral vs. Strep Pharyngitis

Can we reliably distinguish viral from GABHS pharyngitis by history and physical alone? The short (and perhaps unpopular) answer is no. Experienced physicians are about 50%-60% accurate in their clinical ability to diagnose GABHS pharyngitis. However, we can use some data to help raise or lower our suspicion for GABHS. Figure 1 shows the clinical and epidemiologic findings associated with GABHS and viral pharyngitis.⁶

The most widely accepted prediction rule to help clinically distinguish the presence of GABHS pharyngitis is the Centor criteria. For the Centor score, 1 point is assigned for each of these clinical characteristics: history of fever, anterior cervical lymphadenopathy, exudates on the tonsils, and absence of a cough.⁷

In a typical adult population of sore throat patients with a prevalence rate of “strep throat” infections of 5%-15%, a Centor score of 0-1 means a patient has a less than 5% likelihood of having a GABHS infection. A score of 2-3 means a 5%-30% likelihood, while a score of 4 means an approximately 30%-60% likelihood of GABHS infection.

The Centor criteria are most useful in “ruling out” the possibility of a GABHS infection if the score is 0-1.¹ Similarly, patients with “common cold” symptoms (runny or congested nose, mild cough) in addition to their sore throat symptoms have a very low likelihood of having a GABHS infection and do not require antibiotic therapy. From this estimation, we can see that a large number of patients with a Centor score of 2-3 or even 4 will receive unnecessary antibiotics.

Many societies have weighed in on this issue. There are three options recommended to help us make a diagnosis.⁸ Patients with a Centor score of 0 or 1 need no testing and should be treated symptomatically. For others:

• Do a rapid antigen test in patients with scores of 2, 3, or 4 and prescribe antibiotics only for those with positive results.
• Do a rapid antigen test for strep in patients with scores of 2 or 3. Patients with positive test results and those with a Centor score of 4 (no testing) get antibiotics.
• Do no testing and give antiobiotics to patients with Centor scores of 3 or 4.

Obviously, there are drawbacks to all of these approaches. Some patients not treated based simply on a Centor score of 2 risk undertreatment. On the other hand, children and adolescents aged 5-15 years have carriage rates as high as 25% during “strep throat season,” so treating all who have a positive rapid antigen test (or throat culture) will result in overtreatment of patients with viral pharyngitis and strep carriage. However, any approach that relies on the Centor score, rapid antigen testing, or a combination of the two is superior to, and more rational than, the approach of just giving all patients antibiotics.

Rapid Strep Test vs. Throat Culture

A throat culture is considered the “gold standard,” with sensitivity of approximately 95%. However, rapid strep testing has been recently advocated by many societies because:⁹

• Newer assays have adequate sensitivity (90%-95%) and specificity (90%-99%).⁸
• Reduces unnecessary short-term treatment while waiting for cultures.
• Potentially reduces need for callbacks.
• Allows timely initiation of antibiotics, reducing acute morbidity and contagion.
• Has high patient satisfaction despite wait times.

In contrast, the American Academy of Pediatrics (AAP) recommends routine rapid antigen testing and routine culture in all children with suspected strep pharyngitis because of a higher incidence of GABHS infection and the higher sensitivity of a throat culture. What is the “best practice” at this time for my patient? Overall, following a clinical decision rule and/or selective testing to help identify patients who are most likely to benefit from antibiotic treatment appears to be the best course of action.⁸

Antiobiotics for a GABHS Infection

One of the largest reviews on this subject is from the Cochrane database.¹⁰ The review included trials of antibiotic against control with either measures of the typical symptoms (throat soreness, headache, or fever) or suppurative or nonsuppurative complications. Suppurative complications include acute otitis media, acute sinusitis, and quinsy (peritonsillar abscess), while nonsuppurative complications include acute glomerulonephritis and acute rheumatic fever (ARF).

What did the reviewers find? Throat soreness and fever were reduced by antibiotics by about 50%, with the greatest difference seen at 3-4 days (which correlated to the time when symptoms of 50% of placebo patients had resolved). The overall number need to treat (NNT) to prevent one sore throat at day 3 was 5 (95% confidence interval [CI] 4.9-7.0); at 7 days it was 21 (95% CI 13.2-47.9). Additional subgroup analyses of symptom reduction found that antibiotics were more effective against symptoms at day 3, with a relative risk (RR) of 0.58 (95% CI 0.48-0.71) for GABHS-positive swabs vs. an RR of 0.78 (95% CI 0.63-0.97) if negative. At week 1, the RR with antibiotics was 0.29 (95% CI 0.12-0.70) vs. 0.73 with a control (95% CI 0.50-1.07). For suppurative complications, antibiotics reduced the incidence of acute otitis media (RR 0.30, 95% CI 0.15-0.58) with an NNT of 50, and of peritonsillar abscess (RR 0.15, 95% CI 0.05-0.47) with an NNT of 46.

A more recent national database study of more than 1 million sore throats found a much higher NNT of over 4,000.¹¹ For nonsuppurative complications, no conclusive evidence exists to support the belief that antibiotics protect against acute glomerulonephritis. Several studies found antibiotics reduced ARF by more than two-thirds (RR 0.22, 95% CI 0.02-2.08), with an NNT of 41.

However, a total of 10 of the 16 studies included for the outcome of ARF were conducted in the 1950s. The baseline risk was 0.036, or 1 in 28, with only one controlled study performed in military camps in the 1950s demonstrating possible reduction in ARF.¹² In studies published since 1990, there were no cases of rheumatic fever in 2,484 patients in both treatment and control groups.

If data analysis is restricted to the six studies done since 1975, the maximum risk is not more than 0.3%, or approximately 1 in 345.¹³ The systematic review data reveal that to prevent one case of ARF the NNT is 41, while post-1975 studies have an NNT of 494.¹³ Today, the estimated incidence of rheumatic fever in the United States is 1 in 1 million. Therefore, if we assume the risk is 1 in 1 million, the NNT would be 1,430,000 for ARF.¹³ If only one-third of patients with acute rheumatic fever develop cardiac complications, the NNT increases to more than 1 in 3 million to prevent one case of heart disease due to ARF.

Why does this matter? Disadvantages of treating patients with unnecessary antibiotics include additional expense, risks of therapy with limited benefit (drug allergy reactions and side effects), and concern for increased resistance to antibiotics (especially macrolides or fluoroquinolones). With use of similar estimates as presented, for every 1 million antibiotic prescriptions for “strep throat,” there could be as many as 500 severe (potentially fatal) allergic reactions and 100,000 cases of diarrhea and rash.

Overall, the authors of the Cochrane review concluded that:

• Antibiotics confer modest absolute benefits by shortening the duration of symptoms by only about 16 hours.
• Protecting sore throat sufferers against suppurative and nonsuppurative complications in modern Western society can be achieved only by treating many patients with antibiotics, most of whom will derive no benefit; in contrast, in emerging economies (where rates of acute rheumatic fever are high), the NNT may be much lower for antibiotics to be considered effective.
• Antibiotics reduce bacterial infections, but they can cause diarrhea, rash, and other adverse effects, and communities build resistance to certain antibiotics.

Is There a True “Bottom Line”?

Antibiotics are of limited use for most patients with sore throats. The two main benefits of early antibiotic therapy for GABHS pharyngitis are a modest earlier resolution of the patient’s symptoms and a diminished likelihood of spreading the infection to other people. However, recently updated American Heart Association (AHA) guidelines for the prevention of rheumatic fever (endorsed by the AAP) recommend routine testing of all patients with suspected GABHS pharyngitis (based on clinical and epidemiologic findings; see Figure 1) and antibiotic use only for documented GABHS infection.¹⁴ It will be interesting to see if any major shifts in the current standard recommendation for antibiotics for all suspected or documented GABHS infection will be proposed in an expected updated guideline (projected publication, spring 2011) from the Infectious Diseases Society of America on this controversial issue.

Certain populations require special consideration for antibiotic use. Any patient with a history of rheumatic fever or a family member with suspected or documented strep pharyngitis should receive prompt treatment with antibiotics.^9,15 A second category is the patient who has already started “leftover” antibiotics at home prior to diagnosis; as few as two doses of antibiotics may invalidate GABHS laboratory results.¹⁶ A third category is those with pharyngitis in the setting of a local outbreak of rheumatic fever. Finally, patients with strep pharyngitis that recurs at least 7 days but within 4 weeks of completing prior antibiotic therapy should be considered for an additional course of antibiotics. Patients may be a carrier of GABHS (10%-25% of the U.S. population).²

Alternatively, treatment failure may occur because of medication noncompliance, alternative pathogens, or rare cases with pharyngeal flora producing beta-lactamase. What are the options in these situations? Consider antibiotics if:

• Clinical or laboratory findings suggest GABHS.
• The patient is 5-15 years old and it is a higher-incidence season, such as winter or spring.
• The patient has had repeated, marked clinical response to antibiotic therapy.
• Throat cultures are negative between episodes of pharyngitis (less likely carrier state).¹

Appropriate Antibiotic Selection

Based on cost, narrow spectrum of activity, safety, and effectiveness, penicillin continues to be recommended as the first-line agent by the American Academy of Family Physicians (AAFP), AAP, AHA, IDSA, and the World Health Organization for the treatment of streptococcal pharyngitis.⁸ Oral therapy for 10 days is standard. Despite many years of use, penicillin resistance remains rare and allows for the option of a single-dose intramuscular injection of penicillin G benzathine (Bicillin L-A) or a premixed penicillin G benzathine/procaine injection (Bicillin C-R) to lessen injection-associated discomfort.

Why treat with an antibiotic other than penicillin? The main reason will be an allergy to penicillins. Erythromycin is a suitable alternative, and clindamycin is a recommended second-line agent in patients unable to tolerate erythromycin. In the pediatric population, support continues to grow for using amoxicillin, primarily because of its better taste and less-frequent dosing regimen. Amoxicillin once daily (750 mg for those weighing less than 30 kg, 1,000 mg for those weighing more) may be as effective as a regimen of two to three times per day. Small studies have demonstrated comparable symptom relief, including a recent study of children and adolescents 3-18 years old that showed once-daily dosing to be as effective as twice-daily dosing.^17,18 Although this regimen is being used by some practitioners, especially pediatricians, readers should be aware that once-daily therapy is not approved by the Food and Drug Administration.

Monospot Testing

In general, infectious mononucleosis caused by the Epstein-Barr virus (EBV) occurs most commonly in teenagers and young adults between the ages of 15 and 24 years. It can be very difficult to differentiate clinically presenting symptoms and signs from those of GABHS pharyngitis. A monospot blood test is often negative during the first 1-2 weeks of the illness, and a repeat test may be required if symptoms persist. EBV-specific antibodies to a number of viral antigens can be measured but may unavailable or require lengthy testing times, making them impractical in many clinic or emergency department settings. In general, serologic testing for evidence of mono­nucleosis is recommended in patients with splenomegaly, pharyngitis symptoms persisting for 5-7 days, or GABHS positive or suspected on initial visit treated with appropriate antibiotics and returning with persistent symptoms. ⁹

Making Patients With a “Sore Throat” Feel Better

The use of steroids to reduce symptoms in acute pharyngitis is controversial. Several studies have been performed regarding this issue; they are of mixed quality and were limited to immunocompetent patients.¹⁹ The key issue is that in all studies showing benefit, patients were also treated with antibiotics for documented or presumed GABHS infection. However, a single dose of dexamethasone, betamethasone, or prednisone appears to reduce symptom severity in undifferentiated acute pharyngitis in adults.²⁰ Data for children are less conclusive, with one study reporting modest early benefits in GABHS-positive patients. No significant differences in side effects or complications were found in meta-analyses.19 Onset to relief was at 6-9 hours with steroids vs. 12-18 hours for placebo, and for complete resolution within 24 hours the NNT was 4.²⁰ Studies in patients with infectious mononucleosis have shown benefit in symptom reduction in the first 12 hours, but this benefit appears to disappear at 2-4 days.²¹

For pain relief, effective short-term (less than 24 hours) alternative treatments include nonsteroidal anti-inflammatories and acetaminophen.²² One interesting and very practical finding is that nonmedication interventions—specifically, better doctor to patient communication—had an effect size compared with placebo as large as 93%. Increased courtesy, increase in consultation time from 6 to 10 minutes to discuss diagnosis and treatment plans, and offering a prognosis of when a patient should be feeling better were all cited.²² These may be especially important in patients not receiving antibiotics.

Finally, are there any other alternative treatments we can recommend to our patients? What about a good old-fashioned gargle with a warm salt solution? Many herbs and plant extracts have been promoted as beneficial for sore throats, but there is insufficient evidence to recommend any particular agent.²³

Summary

Sore throats can be a “pain in the neck” for both the patient and the clinician. However, based on available guidelines and treatment options, we can develop a rational game plan to treat the next patient we see with a “sore throat.” The absolute benefits of antibiotics are limited, and a lively discussion regarding their risks and benefits is sure to continue. Our main goals should be symptom relief and patient education.

References

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