Bacterial Pharyngitis

Background

Pharyngitis, or sore throat, is often caused by infection. Common respiratory viruses account for the vast majority of cases (see Viral Pharyngitis), and these are usually self-limited. Bacteria are also important etiologic agents, and, when identified properly, may be treated with antibacterials, resulting in decreased local symptoms and prevention of serious sequelae.

The most common and important bacterial cause of pharyngitis is Streptococcus pyogenes (group A Streptococcus [GAS]). When suspected, bacterial pharyngitis should be confirmed with routine diagnostic tests and treated with various antibiotics. Swabbing the throat and testing for GAS pharyngitis via rapid antigen detection test (RADT) and/or culture should be performed as clinical features alone cannot reliably distinguish GAS pharyngitis from viral pharyngitis. The exceptions to these is when patients present overt clinical features of viral infection including rhinorrhea, cough, oral ulcers, and/or hoarseness, in which case a positive test result might reflect a carriage state.^[1]

If left untreated, S pyogenes pharyngitis may lead to local and distant complications. To a lesser extent, bacteria other than S pyogenes are known to cause pharyngitis, and these are discussed in Causes.

• References

Pathophysiology

Beta-hemolytic streptococci have the ability to cause large zones of hemolysis on blood agar, aiding in microbiological identification.^[2] Lancefield antigens, carbohydrates in the cell wall, provide further differentiation of streptococci. S pyogenes, which contains group A antigens and displays beta-hemolysis, is the most common species referred to as a group A beta-hemolytic streptococci (GABHS). Streptococcus dysgalactiae subspecies equisimilis and some species from the Streptococcus anginosus group may share laboratory characteristics with S pyogenes but do not commonly cause human disease. See the image below.

View Image

Picture of Streptococcus pyogenes at 100 X magnification.

Perhaps the most important virulence factor of GABHS is the M protein. This protein, located peripherally on the cell wall, is required for invasive infection. T cells exposed to this M protein are postulated to cross-react with similar epitopes on human cardiac myosin and laminin, contributing to the pathogenesis of rheumatic heart disease.^[3] This protein provides a potential target for a GABHS vaccine, although successful widespread implementation of such a vaccine remains elusive.^[4] More than 100 M-protein serotypes have been described. Although individuals often develop lifelong immunity to one serotype, re-infection with a different serotype may cause disease.

GABHS contains a hyaluronic acid capsule, which also plays an important role in infection.^[5] Bacteria that produce large quantities of this capsule exhibit a characteristic mucoid appearance on blood agar and may be more virulent.

Certain GABHS exotoxins act as superantigens by up-regulating T cells.^[6] These superantigens can prompt a release of proinflammatory cytokines and may synergize with lipopolysaccharide. It has been speculated that these superantigens evade the pharyngeal immune response, resulting in proliferation of GABHS while permitting immune-mediated elimination of commensal organisms.

Adhesins enable GABHS attachment at sites such as the pharynx. This attachment allows for colonization and competition with normal host flora.

Some strains produce erythrogenic toxins, which cause the rash of scarlet fever in susceptible hosts.

GABHS is spread from person to person through large droplet nuclei.^[7] Consequently, close quarters (eg, barracks, daycares, dormitories) facilitate transmission. In temperate regions, the prevalence of GABHS infection increases in the colder months, presumably because of the tendency of people to congregate indoors. Spread within families is common. The risk of acquiring GABHS from an infected family member is 40%, and nearly one in four of infected individuals eventually exhibit symptoms. Twenty-four hours after appropriate antibiotics are initiated, the patient is no longer considered contagious.

Case reports and in vitro studies have speculated that toothbrushes, orthodontic appliances, and pets may carry and facilitate spread of GABHS,^{[8, 9]} although these claims have not been validated by rigorous in vivo investigation.^[10]

GABHS is also a common cause of erysipelas, cellulitis, and necrotizing fasciitis and has been reported as a cause of pneumonia, empyema, toxic shock syndrome, and lymphangitis. The vast majority of these manifestations do not occur in the setting of pharyngitis.

• References

Epidemiology

Frequency

United States

Acute pharyngitis accounts for approximately 12 million annual ambulatory care visits in the United States. It ranks within the top 20 most-common primary diagnosis groups.^[11]

In temperate climates, GAS pharyngitis occurs most commonly in the winter and early spring.^[1]

International

An estimated 616 million cases of GABHS pharyngitis occur annually worldwide.^[12] Rheumatic heart disease, which may be a consequence of GABHS pharyngitis, is estimated to cause about 6 million years of life lost annually. The burden of rheumatic heart disease disproportionately affects populations from developing countries. In terms of estimated global mortality, GABHS is one of the top 10 pathogens, behind HIV infection and malaria and ahead of tetanus and pertussis.

Mortality/Morbidity

Although GABHS pharyngitis is usually a self-limited entity, on average, a single episode in a child results in 1.9 days absence from school and a parent missing 1.8 days from work to care for the child.^[13] Children with GABHS pharyngitis experience symptoms for an average of 4.5 days.

In addition to symptoms localized to the oropharynx, GABHS pharyngitis may also cause suppurative and nonsuppurative complications. Invasion of nearby structures may cause suppurative complications such as otitis media, sinusitis, peritonsillar abscess, retropharyngeal abscess, and cervical adenitis. Nonsuppurative complications of bacterial pharyngitis include rheumatic heart disease and poststreptococcal glomerulonephritis. These entities are discussed in Complications.

Race

GABHS pharyngitis affects all races.

Sex

GABHS pharyngitis has no sexual predilection.

Age

GABHS pharyngitis is most common in individuals aged 5-15 years, although adults may also acquire the disease.^[14] Streptococcal pharyngitis is very uncommon in children younger than 3 years with the exception of children with risk factors such as an older close or household contact with GAS infection. Acute rheumatic fever is also rare in children younger than 3 years and in adults.

For more information on pharyngitis in children, see the Medscape Reference article Pediatric Pharyngitis.

• References

Prognosis

GABHS pharyngitis is usually a self-limited illness. Throat symptoms resolve within 3-4 days in untreated patients. Administration of penicillin shortly after disease onset may shorten symptoms by 1-2 days.^[15]

• References

Patient Education

Symptomatic relief may be provided by warm saline gargles, throat lozenges, and ibuprofen.

Acetaminophen or ibuprofen can be used for fever relief.

Patients with bacterial pharyngitis should be instructed to complete a full course of antibiotics, even if symptoms resolve.

• References

History

The signs and symptoms listed below may be seen with many non-GABHS etiologies. Furthermore, individuals with GABHS pharyngitis may have only a few or mild features listed. Conjunctivitis, cough, hoarseness, coryza, diarrhea, anterior stomatitis, discrete ulcerative lesions, and a viral exanthem are all more consistent with an etiology other than GABHS, particularly viral. Recent studies have also included rhinorrhea and conjunctival infection as viral features.^[16] Signs and symptoms include the following:

• Sore throat, usually with sudden onset
• Odynophagia
• Headache
• Nausea, vomiting, and abdominal pain

• References

Physical

Physical examination may reveal the following:

• Fever
• Tonsillopharyngeal erythema
• Exudates (patchy and discrete)
• Beefy red swollen uvula
• Lymphadenopathy (tender anterior cervical nodes)
• Petechiae on the palate
• Scarlatiniform rash (In susceptible hosts, this usually manifests within the first two days of symptoms and causes a finely papular, blanching, and erythematous rash. The neck is often first affected and then spreads along the trunk and limbs. Resolution, often at 3-4 days, occurs in roughly the same order of appearance and often results in desquamation of the involved areas.)

Predictive models have been developed to help determine the likelihood of GABHS pharyngitis based on the presence of fever, swollen tender anterior cervical lymph nodes, and tonsillar exudates and the absence of cough. Scores have been used to distinguish which patients merit further laboratory evaluation or treatment. The use of such clinical algorithms has been the source of much debate.^{[1, 17]} These score systems were originally developed prior to the availability of RADTs and might be helpful in determining which patients to test for GAS pharyngitis but lack sufficient specificity to decide which patients need antibiotic therapy and might result in unnecessary use of antibiotics.^[1]

• References

Causes

Viruses cause the vast majority of pharyngitis cases. Common agents include coronavirus, rhinovirus, adenovirus, parainfluenza, influenza, Epstein-Barr virus, cytomegalovirus, and HIV.

GABHS accounts for 15%-30% of pharyngitis cases in children and 5%-10% of cases in adults.^[1] Bacteria other than GABHS that may cause pharyngitis are discussed below.

Group C and G streptococci

Like GABHS, these pathogenic bacteria cause beta-hemolysis, form large colonies, and produce an M protein, yet neither is detected with RADTs, as they lack the group A antigen, which is the target of the test.

Pharyngitis caused by either of these non-GABHS streptococci have a clinical presentation similar to that of GABHS pharyngitis and should be considered in patients with worsening symptoms and an initial negative RADT result. They have been reported in epidemics, particularly in semi-closed populations such as military installations or schools^{[18, 19, 20]} and in sporadic pharyngitis in college students.^[21]

These bacteria are an uncommon cause of acute pharyngitis in pediatric patients.^{[22, 23]} They have not been associated with the development of acute rheumatic fever.^[24] Diagnosis can be achieved with a bacterial throat culture and identification based on Lancefield antigens.^[25]

The prevalence of group C Streptococcus infection among primary care patients presenting with sore throat was reported to be 6.1% (95% CI, 3.1%-9.2%).^[26]

Arcanobacterium haemolyticum

This gram-positive rod is an uncommon cause of pharyngitis and tonsillitis and accounts for 0.5% and 3% of cases.^[27] Clinical manifestations are similar to those of GABHS pharyngitis, although about half of patients with A haemolyticum pharyngitis develop a rash, which typically starts on the extensor surfaces; spares the palms, soles, and head; and moves centrally to involve the trunk with a maculopapular or scarlatiniform appearance.

A haemolyticum exhibits variable susceptibility to penicillin and is identified more easily on human or rabbit blood agar than on sheep agar, the media traditionally used to identify GABHS. It is more common in adolescents and young adults.^[28] Erythromycin is the treatment drug of choice.^[27]

Neisseria gonorrhoeae

Infection with this pathogen is associated with oral-genital contact and is often asymptomatic.^[29] N gonorrhoeae may be identified using chocolate or Thayer-Martin agar.^[30] Nucleic acid amplification tests from throat rinses appear to be a promising alternative.^[31] Because of increasing rates of fluoroquinolone resistance, ceftriaxone is now the only recommended option for treatment of pharyngeal gonorrhea.^[32] Treatment aimed at Chlamydia trachomatis is also recommended, since co-infection is common.

Mycoplasma pneumoniae

This atypical bacterium is increasingly being identified as an etiologic agent of pharyngitis.^[33] M pneumoniae pharyngitis may be associated with pulmonary findings.^[34]

Yersinia species

Both Yersinia enterocolitica and Yersinia pestis may cause disease. Pharyngeal plague has been linked to the consumption of camel meat.^[35]

Chlamydia trachomatis and Chlamydophila pneumoniae

Both of these organisms are rare causes of pharyngitis.^{[33, 31]}

Francisella tularensis (oropharyngeal tularemia)

The causative organism is a gram-negative pleomorphic coccobacillus that can be acquired by ingestion of contaminated water or inadequately cooked game meat. It is an uncommon cause of pharyngitis and tonsillitis in the United States and is usually accompanied by lymphadenitis and severe exudative stomatitis.^[36]

Corynebacterium diphtheriae

Toxigenic strains of this gram-positive bacillus are common causes of croup.^[37] Young patients with C diphtheriae pharyngitis often exhibit inspiratory stridor, sternal retraction, and a barking cough. In severe cases, a membrane formation may impair breathing. The incidence of C diphtheriae pharyngitis in developed countries is low because of high immunization rates.

Fusobacterium necrophorum

This is an anaerobic gram-negative bacillus that can be isolated from the oropharynx of healthy individuals but that has been associated with sore throat.^[38] It can also cause life-threatening disease, including Lemierre syndrome or postanginal sepsis (internal jugular vein thrombophlebitis, septic pulmonary emboli, and bacteremia.^[39] Some studies also suggest a role for this bacterium in recurrent or persistent sore throat.^{[40, 41]} However, it should always be considered if a patient presents with severe pharyngitis.^[42] It is more common in adolescents and young adults.

The prevalence of Fusobacterium necrophorum infection among primary care patients presenting with sore throat was reported to be 19.4% (95% CI, 14.7%-24.1%).^[26]

• References

Complications

GABHS infection may result in suppurative or nonsuppurative complications.

Local complications: These result from untreated infection that spreads to adjacent sites. Some of the more common of these suppurative infections include retropharyngeal abscess, peritonsillar abscess, sinusitis, cervical lymphadenitis, otitis media, and mastoiditis.

Acute rheumatic fever: This disorder usually occurs 2-4 weeks after an episode of pharyngitis. Administration of proper antibiotics up to 9 days after the onset of pharyngeal symptoms has been shown to prevent this manifestation.^[43]  Major manifestations of acute rheumatic fever include carditis, polyarthritis, chorea, erythema marginatum, and subcutaneous nodules. Minor criteria include fever, polyarthralgia, elevated leukocyte count, elevated erythrocyte sedimentation rate, and prolonged P-R interval. Current incidence of this complication after endemic infection is unknown but believed to be substantially less than 1%.^[44]

Rheumatic heart disease: This is the chronic valvular manifestation of acute rheumatic fever. The mitral valve is the site most often affected, and either regurgitation or stenosis may result.^[45]  In individuals with rheumatic heart disease, long-term secondary prophylaxis, often with benzathine penicillin, decreases the risk of subsequent episodes of acute rheumatic fever and further heart damage.

Poststreptococcal glomerulonephritis: This usually occurs 1-3 weeks following GABHS pharyngitis. Poststreptococcal glomerulonephritis, which may also follow a GABHS skin infection, has not been shown to be preventable with proper administration of antibiotics. Patients often present with hematuria, edema, and hypertension.

• References

Approach Considerations

The probability that beta-hemolytic streptococci is causing the tonsillopharyngitis can be estimated using a diagnostic scoring system.^[46]

The Centor score is a tool that was developed to help distinguish GAS pharyngitis from viral pharyngitis, so that antibiotics can be appropriately prescribed. It is calculated by assigning one point for each of the following:^{[46, 47]}

• Fever
• Absence of cough
• Presence of tonsillar exudates
• Swollen, tender anterior cervical nodes

The Centor score can range from 0 to 4.^{[46, 47]}

The McIsaac score modifies the Centor score by taking into account the differences in incidence of GAS infection in children versus older adults. The Centor score is used, but one point is added if the patient is younger than 15 years, while one point is subtracted if the patient is aged 45 years or older.^{[46, 47]}

A score of 2 or more should prompt the clinician to perform a pharyngeal swab for rapid testing or bacterial culture to evaluate for beta-hemolytic streptococci. If the score is 3 or more, it would be reasonable for the clinician to treat as GAS pharyngitis. Routine blood tests for acute tonsillopharyngitis are unnecessary. Antistreptolysin O (ASO) testing and other antistreptococcal antibody testing provide no additional help in acute tonsillopharyngitis and so should not be performed.^{[46, 47]}

The Centers for Disease Control and Prevention (CDC) and the American College of Physicians-American Society of Internal Medicine (ACP-ASIM) endorse the Centor score to determine the risk of GAS infection and to guide the management of acute pharyngitis in adults, as shown in Table 1.^[47]

Table 1. CDC/ACP Acute Pharyngitis GAS Testing and Treatment Recommendations Based on Centor Score^[47]

View Table

See Table

The American Academy of Family Physicians also recommend the Centor score, as well as the FeverPAIN score as another validated clinical decision tool. The FeverPAIN scale for pharyngitis is discussed in Table 2.^[48]

Table 2. FeverPAIN Scale for Pharyngitis^[48]

View Table

See Table

For a score of 0 or 1, no testing or treatment is recommended, although a backup throat bacterial culture can be considered if the patient is aged 3-15 years.

For a score of 2 or 3, a rapid antigen detection test is recommended.

For a score of 4 or 5, empiric antibiotic therapy is recommended.

• References

Laboratory Studies

The clinical features of GABHS pharyngitis overlap significantly with that caused by non-GABHS. Microbiological testing provides data to help determine who may benefit from GABHS-directed therapy. Laboratory evaluation of pharyngitis falls into two broad categories: rapid antigen detection tests (RADT) and throat culture.^[49] A throat culture is demonstrated in the video below.

View Video

Throat swab. Video courtesy of Therese Canares, MD; Marleny Franco, MD; and Jonathan Valente, MD (Rhode Island Hospital, Brown University).

RADTs offer the advantage of a speedy diagnosis, allowing for the proper administration, as well as proper withholding, of antibiotics. Drawbacks of RADTs include a higher cost and lower sensitivity compared with culture. While throat culture remains the gold standard for diagnosis of GABHS pharyngitis, it has a 24-48 hour turnaround time and entails more technical involvement. Both RADTs and throat culture cannot be used to differentiate between infection and colonization and, in some cases, may influence a physician to overuse antibiotics. For example, a child with coronavirus pharyngitis and GABHS colonization may be prescribed antibiotics based on a false–positive RADT result. No matter what type of test is used in the outpatient setting, judicious selection of patients to be screened is imperative in order to avoid a large number of false-positive results.^[50]

Samples for RADT or throat culture should be obtained from the posterior pharynx or tonsils. Samples from the oral cavity result in a greatly reduced sensitivity.

Test of cure is not usually indicated except in special situations,^[1] including the following:

• Patients with a history of rheumatic fever
• Patients who live in a community with an increased incidence of rheumatic fever or poststreptococcal glomerulonephritis
• Patients involved in outbreaks of GABHS pharyngitis in closed or semiclosed communities

Test of cure should also be considered in members of a family in whom "ping-pong" spread is presumed.

Antistreptococcal antibody tests have no role in the diagnosis of acute bacterial pharyngitis. However, they may be used to confirm a history of exposure to GABHS in patients with suspected poststreptococcal glomerulonephritis or acute rheumatic fever.

Rapid antigen detection tests ^[51]

See the image below.

View Image

Rapid antigen detection test for group A beta-hemolytic streptococci.

All RADTs yield high specificity, allowing for prompt treatment of GABHS pharyngitis without the concern of false-positive results.

Initial RADTs relied on latex agglutination to identify cell wall carbohydrates obtained after acid extraction, a method associated with low sensitivity.

Newer RADTs use optical immunoassay (OIA) technology to identify cell wall carbohydrates. These yield a sensitivity that may be similar to that of throat culture. Nevertheless, before removing confirmatory throat cultures from any given clinical practice, verification of increased sensitivity is recommended.

A newer generation of rapid tests uses nucleic acid identification to identify GABHS-specific sequences. Such assays yield a specificity of 95%-100% and sensitivity in the range of 86%-95%. Although these tests provide an answer in hours, they rely on equipment not available in most outpatient settings and often need to be performed at a location other than the office.

Recent evidence showed that, without RADT, antibacterials are prescribed inappropriately in 41.6% of cases. RADT decreases this number to 11%.^[52]

Throat culture

Considered the criterion standard of GABHS pharyngitis diagnosis, throat culture involves obtaining a sample from the posterior pharynx and tonsils and plating on sheep blood agar.

Bacitracin disks aid in differentiation of GABHS from other beta-hemolytic streptococci. A large zone of inhibition is found around GABHS but not around non–beta-hemolytic streptococci.

Cell wall carbohydrate detection assays, applied directly to the cultured bacteria, may also differentiate GABHS from other streptococci.

• References

Imaging Studies

Imaging studies have no role in the diagnosis of bacterial pharyngitis. Lateral neck films may help to confirm the diagnosis of acute epiglottitis. CT scanning may aid in the diagnosis of some of the suppurative complications of pharyngitis, including retropharyngeal or deep neck abscesses, lymphadenitis, and sinusitis.

• References

Approach Considerations

The following are the treatment goals for tonsillopharyngitis:^[46]

• Symptom relief
• Complication avoidance
• Decreasing the number of disease-related school or work absences
• Management expense reduction
• Quality of life improvement

Conservative treatment is first-line, while surgical management should be performed only if a patient meets recommended indications (see below).^[46]

• References

Medical Care

Overzealous prescription of antibiotics for pharyngitis has been estimated to cost health payers $1.2 billion annually.^[53] Therefore, treatment of GABHS pharyngitis should be initiated only after confirmation with a RADT or throat culture.^[1] Alternatively, treatment in high-risk patients may be started before throat culture results are available, but antibiotics should be stopped if the culture returns negative results. Even though most cases of GABHS pharyngitis resolve after 3-4 days without treatment, antibiotics decrease the likelihood of local suppurative complications and acute rheumatic fever. Oral antibiotics should be administered for 10 days, although many recent studies show similar efficacy with shorter courses.^{[54, 55]} Antibiotic therapy does not decrease the likelihood of poststreptococcal glomerulonephritis.

Oral penicillin V remains the preferred antibiotic to treat GABHS pharyngitis.^[1] Amoxicillin is often prescribed and is an acceptable first-line agent because of its narrow spectrum, the ease of once-daily dosing, and improved palatability, especially for children. Both antibiotics are equally efficacious.^{[56, 57, 58]}

In vitro, no isolate of GABHS has ever been resistant to penicillin. Advantages of oral penicillin include its narrow spectrum, low cost, infrequent adverse effects, and proven track record.

A recent Cochrane meta-analysis evaluating patient outcomes on different antibiotics for group A streptococcal pharyngitis concluded that there is insufficient data to show clinically meaningful differences between antibiotics for GABHS tonsillopharyngitis and that, considering the low cost and absence of resistance, penicillin can still be recommended as first choice.^[59] Nevertheless, GABHS is sensitive to many other antibiotics, which can be considered as alternative choices based on numerous factors.

The ACP, American Academy of Pediatrics (AAP), and Infectious Diseases Society of America (IDSA) all agree that the antibiotics of choice for acute pharyngitis are oral penicillin V (for 10 days), intramuscular penicillin G benzathine (single dose), and oral amoxicillin (10 days), which is as efficacious as penicillin but more palatable, especially in children.^[48]

Circumstances dictating that a choice other than penicillin V should be used

Compliance: Oral penicillin requires multiple daily doses and a 10-day course. In patients unlikely to adhere to this regimen, one dose of intramuscular benzathine penicillin provides a depot that releases medication over the course. Recent reports have supported the use of once-daily amoxicillin and verified its noninferiority to twice-daily penicillin^[56] or twice-daily amoxicillin.^[57] Azithromycin, cefdinir, and cefpodoxime may all be given in 5-day courses, although none of these medications should be considered a first-line agent given their extended spectrum and risk for promoting antibiotic resistance.^{[1, 60, 61]} Furthermore, although no differences in treatment outcomes have been found between macrolides and penicillin, children experienced more adverse events with macrolides.^[59]

Palatability: Some young children find oral penicillin unpalatable. Taste tests and many doctors’ experiences have shown amoxicillin to be much better tolerated.^[62] Amoxicillin’s similar spectrum and low cost make it a reasonable substitute.

Allergy: In patients with an immunoglobulin E (IgE)–mediated penicillin allergy, antibiotics that contain a beta-lactam ring (cephalosporins, amoxicillin) should be used with caution. Although cross-reactivity between penicillin and cephalosporins is probably less than 10%, the risk of anaphylaxis justifies the consideration of other viable agents.^[63] In patients with nonanaphylactic reactions to penicillin a first generation cephalosporin (Cephalexin, Cefadroxil) is a treatment alternative. In patients with history of severe or anaphylactic reactions to penicillin, macrolides such as azithromycin, clarithromycin, and erythromycin may be used, although resistance has been reported in the United States^[64] and internationally.^[65] Clindamycin is also a reasonable alternative in penicillin-allergic patients, as resistance rates remain less than 1% in the United States.^[66]

The ACP, AAP, and IDSA all agree that a first-generation cephalosporin (for 10 days) should be prescribed to patients with type IV hypersensitivity to penicillin, while clindamycin (for 10 days), clarithromycin (for 10 days), or azithromycin (for 5 days) should be prescribed to patients with type I hypersensitivity to penicillin.^[48] If the patient is allergic or has some form of incompatibility to penicillin, the European Archives of Otorhinolaryngology clinical practice guidelines also suggest cephalosporins or macrolides as alternatives.^[46]

Recurrence: Test of cure is not indicated when pharyngitis symptoms have resolved following treatment. In patients with recurrent symptoms, retreatment with an initial first-line agent (oral penicillin, benzathine penicillin, or a first-generation cephalosporin) is reasonable. Worth noting is the difficulty in differentiating between viral pharyngitis with GABHS carriage and actual GABHS pharyngitis. This becomes even more of an issue in patients with multiple recurrences. Between 5% and 15% of children are asymptomatic carriers during seasons when GABHS pharyngitis is most prevalent.^[67] A positive test result during a time of wellness may indicate GABHS carriage. When multiple recurrences are believed to be due to GABHS infection, clindamycin or amoxicillin/clavulanic acid is indicated.^[1] A 2018 systematic review supports this recommendation because of the superiority of the two drugs to penicillin in terms of eradicating streptococci and nonstreptococci. However, the level of evidence was deemed of moderate quality owing to the risk of bias from two included randomized controlled trials.^[68]

The European Archives of Otorhinolaryngology clinical practice guidelines also recommend oral penicillin as first-line therapy for beta-hemolytic streptococci. Oral cephalosporins (eg, cefadroxil, cephalexin) are the recommended alternatives that can be used for penicillin failure, frequent recurrences, or whenever a more reliable eradication of beta-hemolytic streptococci is needed.^[46]

Pharyngeal carriage

Antimicrobial therapy is not indicated for most pharyngeal GAS carriers. Eradication for carriage may be indicated in the following situations:

• Local outbreak of acute rheumatic fever (ARF) or poststreptococcal glomerulonephritis
• Outbreak of GAS pharyngitis in a closed or semi-closed community
• Family history of ARF
• Multiple ("ping-pong") episodes of documented symptomatic GAS pharyngitis occurring within a family for many weeks despite appropriate therapy

Antimicrobial treatment options that have been shown to be more effective than penicillin monotherapy include clindamycin, cephalosporins, amoxicillin/clavulanic acid, azithromycin, or a combination that includes either penicillin V or G with rifampin for the last 4 days of treatment.^[69]

Delayed antibiotic prescribing

When a patient presents with signs and symptoms that cannot be initially confirmed as viral or bacterial by a healthcare provider, one strategy is to provide a delayed antibiotic prescription. The delayed prescription can be filled by the patient "just in case" the sore throat does not follow the course of viral pharyngitis, instead progressing as bacterial pharyngitis. Symptom control was similar between immediate and delayed antibiotic prescription, with the latter having the potential to decrease antibiotic usage.^[70]

Corticosteroids

A double-blind, placebo-controlled randomized trial conducted in 42 family practices in South and West England enrolled 576 patients who presented with acute sore throat that was deemed to not require immediate antibiotic therapy. Administration of a single 10-mg dose of oral dexamethasone significantly increased the proportion of patients with resolution of symptoms at 48 hours compared with placebo, although not at 24 hours.^[71]

Nonetheless, the authors stressed that the results did not suggest that all patients presenting with sore throat should receive a corticosteroid. In fact, the question was raised: "Is it worth using corticosteroids to treat a relatively harmless disorder?" particularly since a cohort study of more than 1.5 million patients showed that the risks for fractures, venous thromboembolism, and sepsis were significantly higher in those given steroids within 30 days and despite low doses prescribed.^{[72, 73]}

• References

Surgical Care

In rare cases, pharyngitis spreads to adjacent structures and forms abscesses. In these cases, a drainage procedure performed by an interventional radiologist or otolaryngologist should be considered.

Tonsillectomy is one of the most frequently performed procedures in the United States^[68] and United Kingdom.^[74] However, the IDSA does not recommend tonsillectomy if it will be performed solely to reduce the frequency of GAS pharyngitis.^[1] A systematic review showed that tonsillectomy may reduce sore throat frequency in children and adults compared with no surgery but is associated with more morbidity.^[74]

Clinical practice guidelines published in the European Archives of Otorhinolaryngology state that surgical options can be either intracapsular or extracapsular tonsil surgery and can be used for the following:^[75]

• Recurrent acute tonsillitis
• Peritonsillar abscess
• Infectious mononucleosis

Of course, conservative treatment should be first-line. However, the recommendation to use of tonsillectomy for recurrent tonsillitis in children is based on moderate quality of evidence, while the evidence in adults is of low quality. Tonsillectomy in children modestly affects the number of sore throat episodes per year. Data in adults were found to be heterogenous, explaining why tonsillectomy cannot be considered effective yet in these patients. In fact, additional research is still needed to show if tonsillectomy has significant benefit over the nonsurgical treatment of tonsillitis or tonsillopharyngitis.^[75]

In general, tonsillectomy positively affects quality of life, although additional research may better establish this. Conversely, tonsillotomy and similar procedures are associated with much less postoperative pain and bleeding and similar outcomes in the children and young adults. However, the Brodsky scale should be used to evaluate the patient’s tonsil volume; a grade of more than 1 indicates eligibility for tonsillotomy.^[75]

The number of tonsillitis episodes in the preceding 12 months determines the indication to perform tonsillectomy or tonsillotomy. Surgery is not recommended in patients with less than 3 episodes, which means watchful waiting for 6 months is reasonable. However, a patient who has had 6 or more episodes of tonsillitis in the preceding 12 months is considered a candidate for tonsil surgery.^[75]

In patients with peritonsillar abscess, the following are effective treatment methods:^[75]

• Needle aspiration
• Incision and drainage
• Abscess tonsillectomy

Before deciding which surgical method is to be performed, patient compliance and ability to cooperate must be considered. It is also recommended to prescribe antibiotic therapy simultaneously, although additional research on this subject is still being conducted.^[75]

Tonsillectomy of the contralateral side should be performed only in patients who meet criteria for elective tonsillectomy or if the peritonsillar abscess is bilateral.^[75]

Needle aspiration or incision and drainage is preferred if the patient has comorbidities, increased surgical risk, or a coagulation disorder.^[75]

Patients with infectious mononucleosis (viral rather than bacterial pharyngitis) should not undergo routine tonsillectomy for symptom control. Tonsillectomy becomes indicated if clinically significant upper airway obstruction results from inflammatory tonsillar hyperplasia. If the patient has no signs of a concomitant bacterial infection, antibiotics should not be prescribed. In contrast, a steroid may be prescribed to relieve symptoms in patients with infectious mononucleosis.

• References

Consultations

An otolaryngologist should be consulted for local suppurative complications such as peritonsillar abscess and mastoiditis. Tonsillectomy may be considered in recurrent GABHS infection.^{[76, 77]}

An infectious diseases expert may be consulted for patients with immunocompromising conditions or when an agent other than GABHS (eg, HIV) is suspected or confirmed.

• References

Diet

Allow a regular diet as tolerated in patients with bacterial pharyngitis. Warm liquids may provide symptomatic relief.

• References

Activity

Encourage rest during the acute illness.

• References

Prevention

Patients with bacterial pharyngitis should be kept out of daycare, school, or work until 24 hours after the initiation of antibiotics.

Vaccination

Despite the massive disease burden caused by S pyogenes (GAS) infection, no licensed vaccine is available to prevent GAS infection and its complications, particularly rheumatic fever and rheumatic heart disease.^{[78, 79, 80]}

GAS vaccines can be classified into two groups: M-protein–based and non–M-protein–based vaccines. The vaccines undergoing clinical investigation are the N-terminal M-protein–based 26- and 30-valent vaccines and the conserved M-protein vaccines, J8 and StreptInCor vaccines.^{[78, 79]}

GAS vaccines are considered "impeded vaccines" for multiple reasons, including the following:^{[78, 79]}

• Safety reasons (the vaccine antigens may contain autoimmune epitopes that could increase the risk of rheumatic fever in recipients)
• The complexity of the epidemiology of S pyogenes infection (numerous emm types, anatomic location of disease, geographic differences)
• Insufficient return of investment by vaccine manufacturers, as most serious GAS diseases occur in low- and middle-income countries

• References

Further Inpatient Care

Droplet precautions should be observed until 24 hours after the initiation of antibiotics.

• References

Medication Summary

The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications.

• References

Penicillin G benzathine (Bicillin L-A, Permapen)

• Dosing, Interactions, etc.

Clinical Context:  Interferes with synthesis of cell wall by binding to penicillin-binding proteins. Penicillin is the drug of choice to treat GABHS pharyngitis, as recommended by expert committees of the American Heart Association, American Academy of Pediatrics, and the Infectious Disease Society of America, because of proven efficacy, safety, narrow spectrum, and low cost. Preferred for patients unlikely to complete a full 10-d PO course. S pyogenes remains universally sensitive to penicillin.

• References

Penicillin VK (Beepen VK)

• Dosing, Interactions, etc.

Clinical Context:  Treatment of choice for GAS pharyngitis, as recommended by expert committees of the American Heart Association, American Academy of Pediatrics, and the Infectious Disease Society of America, because of its proven efficacy, safety, narrow spectrum, and low cost. Inhibits biosynthesis of cell wall by binding to penicillin-binding proteins. Bactericidal against sensitive organisms when adequate concentrations are reached and most effective during stage of active multiplication. Inadequate concentrations may be ineffective. GABHS remains uniformly susceptible in vitro.

• References

Amoxicillin (Amoxil, Biomox, Trimox)

• Dosing, Interactions, etc.

Clinical Context:  Interferes with synthesis of cell wall mucopeptides by binding to penicillin-binding proteins. Often used in place of oral penicillin VK in young children. Efficacy equal to penicillin, and often chosen because of the unpalatability of the penicillin susp.

• References

Azithromycin (Zithromax)

• Dosing, Interactions, etc.

Clinical Context:  Inhibits RNA-dependent protein synthesis at the 50s ribosome. Can be given as a single daily dose, is better tolerated than erythromycin in patients who are allergic to penicillin, and is effective in a 5-d course. However, much more expensive and should be avoided as first-line therapy in patients with streptococcal pharyngitis. Sporadic resistance has been reported.

• References

Clindamycin (Cleocin)

Clinical Context:  Belongs to the lincosamide class of antibiotics. Binds to the 50s ribosome and prevents bacterial protein synthesis. Is an option for symptomatic patients with multiple, recurrent episodes of pharyngitis proven by culture or rapid antigen testing.

• References

Erythromycin (E.E.S., E-Mycin, Ery-Tab, Erythrocin)

• Dosing, Interactions, etc.

Clinical Context:  Inhibits RNA-dependent protein synthesis at the 50s ribosome. An option in those with severe allergic reactions to beta-lactam antibiotics. Sporadic resistance has been reported.

• References

Cephalexin (Keflex)

• Dosing, Interactions, etc.

Clinical Context:  First-generation cephalosporin that arrests bacterial growth by inhibiting bacterial cell wall synthesis. Bactericidal activity against rapidly growing organisms. Oral cephalosporins are highly effective for streptococcal pharyngitis, and several studies have found them to have slightly higher eradication rates than those of penicillin. Second-line agents in the treatment of patients with GABHS pharyngitis.

• References

Clarithromycin (Biaxin, Biaxin XL)

• Dosing, Interactions, etc.

Clinical Context:  Semisynthetic macrolide antibiotic that reversibly binds to P site of 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl t-RNA from ribosomes, causing bacterial growth inhibition.

Similar susceptibility profile to erythromycin but has fewer adverse effects.

• References

Cefadroxil (Duricef, Ultracef)

• Dosing, Interactions, etc.

Clinical Context:  First generation semi-synthetic cephalosporin, that arrests bacterial growth by inhibiting bacterial cell wall synthesis. Bactericidal activity against rapidly growing organisms.

• References

Class Summary

Oral penicillin is currently the drug of choice for GABHS pharyngitis.^[1] Amoxicillin remains a reliable alternative and offers advantages in terms of easier dosing and increased palatability.

Tetracyclines and trimethoprim/sulfamethoxazole should not be used to treat GABHS pharyngitis owing to higher rates of resistance.

Macrolides have poor anaerobic in vitro activity  so should be avoided if an anaerobe (eg, Fusobacterium) is the suspected pathogen.^[42]

• References