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Guidelines

Acute Pharyngitis – Treatment

Antibiotics

It has been estimated that 60% of adults seen in a United States clinic in 2010 for a complaint of sore throat received an antibiotic prescription, with a trend toward prescribing a broad spectrum of antibiotics (Barnett, 2014). Overtreatment of acute pharyngitis is a major cause of inappropriate antibiotic use that can be avoided through appropriate evaluation and treatment.

Currently, based on the same evidence, there are conflicting recommendations regarding treatment for GAS. In reviewing 17 international guidelines, Van Brusselen (2014) found that nine were pro-treatment (including a medical society from the United States), five favored no treatment and two had special considerations (Van Brusselen, 2014). The ESCMID guideline recommends that antibiotics should not be used in patients with less severe presentation of sore throat, e.g., 0-2 Centor criteria to relieve symptoms. Modest benefits of antibiotics, which have been observed in patients with 3-4 Centor criteria, have to be weighed against side effects, the effect of antibiotics on microbiota, increased antibacterial resistance, medicalization and costs (Pelucchi, 2012). The IDSA still advises antimicrobial treatment for adults and all children with GAS pharyngitis, given possible complications, although rare (Shulman, 2012). The AAP recommends antibiotic therapy for children with pharyngitis confirmed to be caused by GAS (Hersh, 2013).

In reviewing primary literature on treatment of GAS, the work group found several limitations. Many of the studies are on patients with sore throats and suspected but not confirmed GAS. In addition, the randomized controlled trials were all conducted prior to 2000, and several were conducted in the 1950s and 1960s before concerns of bacterial resistance.

Overall, the literature mostly shows that compared to no antibiotics, use of antibiotics with confirmed or suspected GAS may decrease non-suppurative and suppurative complications (Little, 2014; Spinks, 2013; Kenealy, 2011; Robertson, 2005). Evidence is not conclusive but does suggest antibiotics may improve symptoms in adults by one to three days (Spinks, 2013; Kenealy, 2011; Zwart, 2000).

There are no conclusive studies on children. The ones that are available are underpowered. A 2003 small randomized control trial among 156 children ages 4-15 years old found that antibiotics (penicillin) had no beneficial effect on the average duration of sore throat symptoms. Treatable strep complications (i.e., peritonsillar abscess, scarlet fever and impetigo) occurred more often in the placebo group. Given these findings, the authors concluded more prudent antibiotic use should be considered, such as limiting antibiotics to those severely ill or at high risk (Zwart, 2003).

There is some evidence that delayed antibiotics is a possible option that may be provided to patients and/or caregivers. A prospective observational cohort study of 12,829 adults with sore throat found that immediate antibiotic prescription was as associated with fewer complications as delayed prescription of antibiotics. The risk of reconsultation was also reduced by either delayed or immediate antibiotic strategies (Little, 2014). A 2013 systematic review of four randomized controlled trials comparing no antibiotics, immediate antibiotics and delayed antibiotics found there was a small difference favoring immediate antibiotics for relieving fever and pain from sore throat (Spurling, 2013).

Available data show the incidence of acute rheumatic fever (ARF) in the Western countries to be < 1/100,000 children while higher in the developing countries at 50/100,000 on average (Van Brusselen, 2014). It is not clear from research how much of the drop in acute rheumatic fever incidence is due to the increased use of antibiotics in GAS, improved living conditions or a different strain of GAS (Van Brusselen, 2014; Shulman, 2006; Robertson, 2005; Bisno, 1991). However, because the decline in rheumatic fever began before the antibiotic era, it is unlikely that antibiotics alone are responsible for the decreasing incidence (Bisno, 1991).

Peritonsillar abscesses are potential rare complications of GAS. The annual incidence of peritonsillar abscess (PTA) in the United States is approximately 30 per 100,000 persons(Galioto, 2017). Although PTA is generally a polymicrobial infection, GAS is considered a predominant pathogen (Galioto, 2017; Klug, 2017).

Taking into consideration the primary literature, the benefits and harms of antibiotics, as well as the differing recommendations among organizations internationally, the work group recommends taking a shared decision-making approach to the testing and treatment of GAS.

In shared decision-making discussions with patients/caregivers, there are three options to present:

  1. Observation (no antibiotics prescribed)
  2. Immediate antibiotics prescribed
  3. Delayed antibiotics (prescribed with instructions to delay filling the prescription to see if symptoms improve)

If a strategy of delayed antibiotics is chosen, the clinician must give the patient detailed instructions on what symptoms warrant filling the prescription and what symptoms necessitate returning to clinic for re-evaluation. It is important to avoid the situation where a patient fills the prescription for worsening symptoms that are actually indicative of a complication (e.g., abscess).

The work group recommends reviewing the following points when deciding the appropriate treatment plan:

Benefits of antibiotic treatment

  • Improve duration of symptoms by one to three days
  • Decrease dangerous complications, including rheumatic fever

Harms of antibiotic treatment

  • Complications such as rheumatic fever are very rare.
  • Antibiotics have side effects including but not limited to gastrointestinal upset, Clostridium difficile infection and allergic reactions.
  • Repeated antibiotic use may lead to antibiotic resistance.

Antibiotic Considerations

If treating with an antibiotic, it is the consensus of the ICSI work group that penicillin (PCN) is the drug of choice for treatment of culture-positive cases of GAS pharyngitis. In children and patients unable to swallow pills, amoxicillin is an acceptable alternative due to the poor palatability of the penicillin suspension (Lennon, 2008).

In penicillin-allergic patients, options include cephalosprins (for some types of allergies), macrolides and clindamycin. Although macrolides may be an acceptable alternative, clinicians should check their local resistance patterns.

The IDSA (Shulman, 2012), AAP (Hersh, 2013) and ESCMID (Pelucchi, 2012) recommends penicillin or amoxicillin as first-line antibiotics in treatment of GAS. For alternatives for penicillin-allergic patients, the IDSA recommends first-generation cephalosporin, clindamycin or clarithromycin, and azithromycin; the AAP and ESCMID do not list their recommendations.

Although the work group still recommends penicillin as first-line treatment, there is some literature suggesting other classes of antibiotics to be as efficacious as or more efficacious than penicillin (van Driel, 2016; Altamimi, 2012; Sakata, 2008; Pichichero, 2007). Further research is needed.

Duration of Antibiotic Treatment and Follow-Up

It is important to emphasize to the patient that completion of the course of antibiotic is important to reduce risk of recurrence. After initiating a course of an appropriate antibiotic, improvement in symptoms related to GAS pharyngitis should be seen within three to four days.

The IDSA recommends 10 days if treating with penicillin/amoxicillin, first-generation cephalosporin, clindamycin or clarithromycin – five days if treating with azithromycin. The ESCMID recommends two to three times daily dose for 10 days if treating with penicillin. The AAP Clinical Report did not list AAP recommendations.

A 2008 meta-analysis of 11 randomized controlled trials involving patients of any age with GAS diagnosis compared short-course (≤ 7 days) vs. long-course (at least two days longer than short course) treatment with the same antibiotics. It found that in the penicillin group, microbiological eradication rates of GAS were significantly higher with 10 days of treatment vs. five to seven days and that the difference was statistically nonsignificant with cephalosporin treatment. In trials involving children and adolescents (ages < 18 years), microbiological eradication was less likely with short-course treatment. Clinical cure rates were also inferior with the short-course treatment. Adverse events rates did not significantly differ between compared groups (Falagas, 2008).

Return to School for Children

The two available studies on return to school had differing conclusions. A 1993 study of 47 children (ages 4 to 17) with pharyngitis and a positive throat culture for group A streptococci found that 17 (36.2%) of the 47 patients had a positive culture the morning after initiating antibiotic therapy. However, 39 (83%) of the patients became “culture negative” within the first 24 hours. The authors suggest that children with GAS should complete 24 hours of antibiotics before returning to day care or school (Snellman, 1993).

In a study of 111 children with confirmed GAS, 91% did not have detectable GAS on day two, regardless of whether they had received a second dose of amoxicillin that morning. The authors conclude that if treated by 5 p.m. on day one, it is reasonable for children with GAS to return to school on day two (Schwartz, 2015).

There is no evidence on children not treated with antibiotics.

The work group finds it reasonable for children with GAS pharyngitis to return to school 12-24 hours after first dose of antibiotic. If not treated with antibiotics, it is reasonable for children to return to school after they are 24 hours fever free without antipyretic treatment.

History of Rheumatic Fever

An individual with a previous history of rheumatic fever who develops GAS pharyngitis is at high risk for a recurrent attack of rheumatic fever. The infection does not need to be symptomatic to trigger a recurrence. Rheumatic fever recurrence can also occur when a symptomatic infection is optimally treated. Therefore, prevention of recurrent rheumatic fever requires continuous antimicrobial prophylaxis, and GAS infections in family members should be diagnosed and treated promptly (Dajani, 1995).

Symptomatic Care

Over-the-counter pain relievers such as acetaminophen or a non-steroidal anti-inflammatory agent (NSAID) may provide fast and effective relief of sore throat pain (Kenealy, 2011).

Additional treatments that may help with throat pain include lozenges, sipping warm or cold beverages, eating cold or frozen desserts and eating soft foods. Salt-water gargles are frequently used for throat pain. It is not clear that salt water works to relieve pain, but it is unlikely to be harmful.

ICSI

ICSI