Bacterial Pharyngitis

Etiology

Acute pharyngitis is quite common in children and adults. Common noninfectious causes are allergic rhinitis or sinusitis, gastroesophageal reflux disease, smoking or exposure to second-hand smoke, and exposure to dry air. In addition, Kawasaki disease, Behçet syndrome, chemotherapy agents, and angiotensin-converting enzyme inhibitors also produce symptoms of pharyngitis.[2]

GABS are gram-positive cocci arranged in chains or pairs and are the most common bacterial etiology of pharyngitis, producing what is commonly referred to as "strep throat."[3] Transmitted via airborne transmission or ingestion, the only known reservoirs of GABS are human skin and mucous membranes. Infection generally peaks in winter and early spring and is most common in school-age children. Additional causes of bacterial pharyngitis include the following:

• Group C and G Streptococcus: These organisms present identically to GABS, most frequently affect college students and young adults, and are associated with community and foodborne outbreaks.
• Neisseria gonorrhea: A gram-negative coccus generally acquired by oral sexual exposure. Pharyngitis associated with N gonorrhea occurs most commonly in men who have sex with men.[4]
• Chlamydia trachomatis: This gram-negative rod does not typically cause pharyngitis, but the pharynx can be a reservoir for infection.
• Treponema pallidum: A spirochete bacterium transmitted sexually. Pharyngitis is a common presenting symptom in patients with secondary syphilis.
• Arcanobacterium haemolyticum (formerly Corynebacterium haemolyticum): This uncommon cause of pharyngitis is an anaerobic gram-positive bacillus spreading through infected respiratory droplets, especially in adolescents and young adults.
• Fusobacterium necrophorum: A gram-negative rod that often colonizes the oropharynx and is likely a secondary invader rather than a causative pathogen.
• Mycoplasma pneumoniae and Chlamydia pneumoniae: Both spread via respiratory droplets. M. pneumoniae is a short rod with no cell wall and is not visible on gram stain. C pneumoniae is a gram-negative bacteria. Pharyngitis is most common in children and young adults and often occurs with a lower respiratory tract infection.
• Corynebacterium diphtheria: A gram-positive club-shaped bacillus transmitted via infected respiratory droplets. Diphtheria is rare in the United States and other places with high immunization rates.[5][6][7]
• Francisella tularensis: This organism is a gram-negative coccobacillus that causes pharyngeal tularemia. Infection occurs via the skin when handling infected animal tissue or inhaling contaminated dust or aerosols.
• Yersinia pestis: This organism is a gram-negative coccobacillus, transmitted by fleas, that causes the plague. 

Pharyngitis has a broad differential, encompassing both infectious and noninfectious etiologies, thus requiring careful evaluation of symptoms and risk factors. Identifying the underlying cause is essential for appropriate management and prevention of complications.

Epidemiology

Pharyngitis is a widespread complaint in healthcare professionals' offices, emergency departments, and urgent care centers, accounting for approximately 12 million annual visits in the United States.[8] This figure represents 1% to 2% of all outpatient visits. Nearly 50% of these visits occur in children, with the remaining adult cases peaking by age 40.[9][10]

Viral causes account for 70% to 90% of acute cases, primarily driven by rhinovirus, the cause of the common cold. GABS infection constitutes 5% to 15% of cases of acute pharyngitis in developed countries and is more common in school-age children. Group C and G streptococci comprise 5% to 10%, while A haemolyticum accounts for 1% to 2.5% of cases.[11][12]

The exact prevalence of M pneumoniae and C pneumoniae is unknown. Unvaccinated populations or regions of the world where the disease remains endemic confine cases of diphtheria. Most pharyngeal infections with N gonorrhea are asymptomatic. Studies reveal the prevalence of pharyngeal gonorrhea in men who have sex with men is approximately 15%.[13] Antibiotic prescriptions are given to 49% to 57% of children and 64% of adults with pharyngitis, often exceeding the prevalence of bacterial infection warranting treatment.[14]  

Pathophysiology

Bacteria invade the mucosal tissues of the pharynx directly. The remaining details of the pathogenesis of bacterial pharyngitis vary based on the underlying pathogen.

Group A β-Hemolytic Streptococcus

GABS has a number of virulence factors that subvert the host's natural immune response. Cell surface proteins, hemolytic toxins, pyrogenic exotoxins, and bacterial structural components all contribute to its virulence. M and M-like proteins help the organism evade phagocytosis and complement deposition.[15] Toxins like streptolysin O further exacerbate tissue damage by affecting platelets and endothelial cells, leading to ischemic injury.[16] Streptolysin S lyses red blood cells. Hyaluronidase aids in infection spread along fascial planes by breaking down hyaluronic acid in connective tissue.

All GABS strains secrete streptokinase and have plasminogen binding sites on the surface. When plasminogen binds, streptokinase converts plasminogen to plasmin and interrupts the coagulation cascade, aiding the spread of infection to deep tissues.[17] Streptokinase is also involved in the development of poststreptococcal glomerulonephritis. Some strains secrete Streptococcus pyogenes nicotinamide-adenine dinucleotidase, which is translocated into the host cells to deplete nicotinamide adenine dinucleotide stores. See StatPearls' companion reference, "Poststreptococcal Glomerulonephritis," for additional information regarding the pathophysiology of poststreptococcal glomerulonephritis. 

Streptococcal pyrogenic exotoxins elicit lymphocyte blastogenesis, exacerbate endotoxin-induced shock, cause fever, dampen antibody synthesis, and function as superantigens. The toxins contribute to fever and shock by reducing the threshold for endotoxin effects, prompting human mononuclear cells to produce tumor necrosis factor-α, interleukin-1, and interleukin-6.

Streptococcal pyrogenic exotoxins also contribute to scarlet fever and toxic shock syndrome by acting as superantigens and stimulating T-cell responses.[18] Binding occurs at both the class II major histocompatibility complex of antigen-presenting cells and the V β region of the T-cell receptor, prompting T cells to synthesize interleukin-1, tumor necrosis factor-α, tumor necrosis factor-β, interleukin-6, and interferon-γ. See StatPearls' companion references, "Toxic Shock Syndrome" and "Scarlet Fever," for more detailed information regarding the pathogenesis of these complications related to GABS infection. 

Other Bacterial Causes

Less common bacterial agents that cause acute pharyngitis include C diphtheria, N gonorrhea, T pallidum, and M pneumoniae. Each of these pathogens presents distinct pathophysiological mechanisms, influencing both diagnosis and treatment approaches.

Corynebacterium diphtheria

Diphtheria symptoms result from local respiratory tract inflammation and the effects of exotoxin both locally and systemically. The toxin binds to cell membrane receptors and disrupts protein synthesis by inactivating elongation factor 2, leading to cell death.

Neisseria gonorrhea

N gonorrhea attaches to the host urethral, cervical, or other epithelial cells via type IV pili and other surface proteins. The pili and surface proteins undergo antigenic variation and various other complex processes to avoid detection by the host immune system.[19] Once bound to the host cells, the organism becomes internalized, multiplies, and divides intracellularly, protecting itself from the immune system and the local environment. Gonococcal infection dampens the host's immune response, preventing the formation of protective immunity against future infections.

Treponema pallidum

T pallidum causes infection wherever inoculation occurs. Primary syphilis presents as a painless chancre at the site of inoculation after an incubation period of 3 to 6 weeks. The chancre initially contains polymorphonuclear leukocytes, which are quickly replaced by T lymphocytes. Concurrently, the host develops a humoral immune response, leading to the development of antibodies detected early in the disease course. While the immune response eliminates the chancre, it does not control the dissemination of the spirochete throughout the body in untreated patients. 

Mycoplasma pneumoniae

The underlying pathophysiology of M. pneumoniae pharyngitis is not fully understood. M pneumoniae has a selective affinity for the respiratory epithelium. Once bound, M pneumoniae secretes hydrogen peroxide and superoxide, which damages the epithelial cells and their cilia. Some remain on the cell surface, and some can invade the host cells, protected from the host's immune response.[20] Extrapulmonary manifestations like hemolysis and encephalitis may be due to antibodies produced against the glycolipid antigens of M pneumoniae that cross-react with human red cells and brain cells and act as autoantibodies. See StatPearls' companion references, "Plague" and " Tularemia," for specific details regarding the pathophysiology of Y. pestis- and F tularensis-induced disease.

Recognizing the diverse bacterial causes of acute pharyngitis is essential for effective treatment. Each pathogen's unique infectious mechanisms require tailored approaches to ensure proper management and reduce the risk of complications.

History and Physical

The initial history and physical examination help clinicians exclude potentially life-threatening conditions and identify treatable causes of pharyngitis. Key historical features for diagnosing pharyngitis include the rapidity of onset and the presence or absence of symptoms such as respiratory distress, fever, and fatigue. Additional relevant factors are recent exposure to sick contacts, history of immunocompromised conditions, vaccination and travel history, sexual history, and previous episodes of pharyngitis. Fever suggests an infectious cause, and respiratory distress indicates an obstructive process like epiglottitis or retropharyngeal or peritonsillar abscess. Pharyngitis, fever, and severe fatigue may indicate infectious mononucleosis. 

Group A β-hemolytic Streptococcus 

Pharyngitis caused by GABS in children 3 years or older typically has an abrupt onset accompanied by fever, headache, and abdominal pain, occasionally associated with nausea and vomiting. Children younger than 3 often do not have a clearly defined case of pharyngitis. These patients may also have accompanying nasal congestion and discharge. Infants younger than 1 year often present with fussiness, decreased appetite, and low-grade fever. These patients often have a family member or daycare contact with GABS. Adults tend to present with an acute-onset sore throat and fever.

Classic physical examination findings are exudative tonsillopharyngitis, enlarged tender anterior cervical lymph nodes, petechiae on the palate, and a strawberry tongue. Additionally, some patients may have a fine papular rash that begins in the groin and axilla, followed by spread to the trunk and extremities. The affected areas eventually undergo desquamation.[21] 

Treponema pallidum

Primary syphilis presents as a chancre, or painless ulceration, at the site of inoculation. Approximately 25% of patients develop secondary syphilis, a systemic illness marked by rash, fever, headache, myalgias, pharyngitis, and gastrointestinal symptoms. Most patients also have posterior cervical, axillary, inguinal, and femoral lymphadenopathy. Epitrochlear nodes highly suggest the diagnosis. The rash, the most characteristic feature, is macular or papular and symmetric, involving the entire trunk and extremities, including the palms and soles.[22] 

Mycoplasma pneumoniae 

M pneumoniae presents in an atypical fashion for bacterial pharyngitis. Patients may experience symptoms similar to a viral upper respiratory infection, like a nonexudative sore throat, coryza, headache, ear pain, and a prolonged cough.[23] Physical examination findings may include pharyngeal edema, wheezing, otitis media, and other symptoms consistent with an upper respiratory infection. Others may have pharyngitis associated with pneumonia. Pneumonia associated with M. pneumoniae typically has a gradual onset, and the lung examination may be normal initially, with rales and wheezing developing later in the course. 

Chlamydia Pneumoniae 

C pneumoniae can cause various infections, including pharyngitis, laryngitis, otitis media, and bronchitis. In conjunction with pneumonia, upper respiratory symptoms like pharyngitis, laryngitis, or sinusitis may signify a C pneumoniae infection.

Corynebacterium diphtheria

Like GABS, diphtheria presents with a sore throat, malaise, cervical lymphadenopathy, and fever. Though the onset of diphtheria is gradual, additional symptoms may be hoarseness, cough, and purulent nasal discharge. The formation of a pseudomembrane can progress, causing respiratory stridor and death. Initially, patients exhibit mild pharyngeal edema and erythema followed by isolated gray and white exudate spots—approximately 33% progress to form a coalescing, tightly adherent pseudomembrane that bleeds with scraping.

Francisella tularensis

Pharyngeal tularemia presents with fever, severe sore throat, and swelling in the neck. Physical examination findings are exudative pharyngitis and tonsillitis with cervical lymph node enlargement. Distinguishing features are pharyngeal or tonsillar ulcers and a pharyngeal membrane mimicking diphtheria.[24]

Yersinia pestis

Y pestis most commonly presents as acute febrile lymphadenitis or bubonic plague. Rarely, if the patient has ingested Y pestis, the plague can manifest as pharyngitis and tonsillitis associated with anterior cervical lymphadenitis.[25]

Evaluation

General Evaluation

Most of the evaluation for acute pharyngitis encompasses a comprehensive history and physical examination with testing in select patients. Clinicians begin with assessing vital signs for fever and evidence of clinical instability. A thorough otolaryngological examination evaluates the ears, conjunctiva, and nares for associated findings or referred symptoms mimicking pharyngitis.

Evaluation of the oropharynx and neck should assess for tonsilar and pharyngeal erythema, swelling, and exudates along with lymphadenopathy. Exudates or a pseudomembrane favors a bacterial etiology, as do swollen and tender anterior cervical lymph nodes. Conjunctivitis, swelling of the nasal turbinates, oral ulcers, and postnasal drip favor nonbacterial etiologies.[26] A skin examination revealing a red rash that feels like sandpaper indicates scarlet fever and GABS infection. Other rashes may suggest viral respiratory infections or syphilis.

When evaluating patients with acute pharyngitis, the initial step is to exclude life-threatening conditions like diphtheria or an abscess in the peritonsillar, submandibular, or retropharyngeal spaces requiring immediate intervention. These patients will be toxic-appearing, with fever and rigors. Additional findings may include the following:

• A muffled voice, often referred to as a "hot potato" voice
• Hoarseness
• Drooling
• Stridor
• Sitting in a "tripod" position
• Tachypnea, dyspnea, or retractions
• Bulging of pharyngeal wall, soft palate, or floor of the oropharynx
• Crepitus
• Trismus
• Stiff neck

Clinicians establish the diagnosis of viral pharyngitis based on the presence of cough, nasal congestion, conjunctivitis, coryza, oral ulcers, and viral exanthems. The associated complications and treatments differ for respiratory viral and bacterial pharyngitis. Thus, distinguishing between these conditions is essential.

Group A β-hemolytic Streptococcus Testing

Evaluating acute pharyngitis involves identifying specific symptoms and risk factors to determine the appropriate diagnostic tests. Testing decisions are guided by clinical criteria that help assess the likelihood of GABS infection and other causes.

Who to test

Adults with symptoms consistent with GABS pharyngitis like acute symptom onset, fever, tonsillopharyngeal or uvular edema, anterior cervical lymphadenitis, patchy tonsillar exudates, scarlatiniform skin rash, strawberry tongue, or a known exposure to GABS without typical respiratory virus symptoms should undergo microbiological testing for GABS. The Centor criteria help clinicians determine which adults to test if the decision is unclear. The Centor criteria include the following:

• Tonsillar exudates
• Tender anterior cervical lymphadenopathy
• Fever
• Absence of cough

Patients receive 1 point for each criterion they meet. Individuals who meet 3 or more criteria warrant testing for GABS.[27][28] Patients with fewer than 3 of these manifestations are less likely to have GABS pharyngitis, making further testing unnecessary. Clinicians should remember that the Centor criteria have low sensitivity, and they should not bypass their clinical impressions to determine the need for antibiotic therapy. The McIsaac criteria derive from the original Centor criteria but account for age differences by adding a point for patients aged 3 to 14 and subtracting a point for patients aged 45 or older.[29]

The FeverPAIN criteria include fever, tonsillar exudates, severe inflammation, onset within 3 days, and the absence of cough or coryza. Again, patients meeting fewer criteria (0 to 1) are unlikely to have strep infections, while those meeting more criteria (4 or more) are more likely to be infected.[30] Clinical scoring systems for GABS are insufficiently sensitive or specific to eliminate the need for microbiologic testing in children and adolescents with suspected GABS.[31] The following list describes the parameters for testing in children and adolescents: 

• Children 3 years or older and adolescents with pharyngeal erythema, edema, and exudates or a scarlatiniform rash on physical examination
• Children younger than age 3 with prolonged nasal discharge, tender anterior cervical adenopathy, and a low-grade fever of 101 °F (38.3 °C) or less, especially if they have a known GABS exposure
• Children with suspected acute rheumatic fever or poststreptococcal glomerulonephritis
• Any child with a history of acute rheumatic fever and a household member with a GABS infection

Patients who warrant testing for GABS can undergo either a sensitive RADT or a NAAT. Clinicians should collect specimens before beginning antimicrobial treatment and vigorously swab both tonsils or tonsillar fossae in patients without tonsils and the posterior pharynx. Accurate results are highly dependent on the collection of an adequate inoculum. Adults and older adolescents have a lower incidence of GABS pharyngitis than children and younger adolescents and an extremely low risk of developing acute rheumatic fever. Consequently, a follow-up throat culture for confirmation is unnecessary if either test returns a negative result. A confirmatory throat culture is necessary in children if the result of the GABS rapid test is negative.[32] 

Given NAAT's high sensitivity and specificity, clinicians can also use it for confirmation. RADTs have a sensitivity of 77% to 92% and a specificity of 88% to 99%. However, solely using this test results in some false negative results unless clinicians follow with a confirmatory throat culture.[33] For this reason, adults who are at higher risk for severe infection or complications from GABS pharyngitis, closely interact with others at risk for complications, live in college dorms where acute rheumatic fever is endemic, or potentially have GABS despite a negative RADT result should undergo a throat culture or NAAT testing. Clinicians do not typically treat empirically while awaiting throat culture results.

Testing for other bacterial causes

Part of evaluating acute pharyngitis includes gathering historical information about sexual activity, potential blood-borne pathogen exposure, and recent intravenous drug use to assess the risk of HIV or other sexually transmitted infections. HIV and N gonorrhea are the 2 most frequent causes of sexually transmitted pharyngitis.

Symptoms of acute HIV infection include fever, pharyngitis, adenopathy in the cervical, axillary, and inguinal regions, headaches, myalgias, rash, and mucocutaneous ulcerations. Testing for suspected early HIV infection requires both a combination antigen/antibody test and an HIV viral load assessment. Clinicians should repeat testing in 1 to 2 weeks if initial tests are negative, but suspicion remains high. A negative antigen/antibody test with a positive HIV viral load suggests acute infection. A viral load of less than 100 copies/mL may indicate a false positive, necessitating repeat testing. A second positive viral load confirms infection.

Pharyngeal gonorrhea and chlamydia are often asymptomatic. Consequently, NAAT swab testing is recommended for patients at increased risk or when acute pharyngitis does not respond to standard treatment.[34] Culture serves as an alternative. Increased risk for syphilis infection is seen in men who have sex with men and patients with HIV. Syphilis screening traditionally starts with a nontreponemal test, such as the rapid plasma reagin (RPR) test, with confirmation using a treponemal test, like the fluorescent treponemal antibody absorption (FTA-ABS). More recent protocols reverse this order, beginning with a treponemal test, followed by a nontreponemal test for confirmation. This reverse method enhances the detection of early syphilis, cases previously treated, and late or late latent syphilis, where the nontreponemal test may become nonreactive over time.

Patients who do not respond to appropriate therapy may require a routine aerobic pharyngeal culture to test for group C or G streptococci, A haemolyticum, and F necrophorum. For suspected diphtheria, a culture should be obtained from both the membrane and beneath it. A presumptive diagnosis is supported by the appearance of gram-positive rods in a "Chinese character" distribution on gram stain, black colonies with halos on Tinsdale media, and metachromatic granules on Löffler media. Biochemical testing confirms the diagnosis, and additional testing for toxin production is necessary to differentiate toxigenic from nontoxigenic strains of C. diphtheriae. In cases of suspected tularemia, serology should be performed and repeated in 2 to 4 weeks.

Imaging

Imaging should be considered when clinical instability, difficulty swallowing, or restricted neck movement is observed. For epiglottitis, a plain radiograph typically shows an abnormal epiglottis. A retropharyngeal abscess may show some changes on plain radiographs, but computed tomography or magnetic resonance imaging is preferred for a more detailed evaluation. Radiographic findings often include increased thickness of the prevertebral soft tissue, swelling, and gas collections in the retropharyngeal space, leading to anterior displacement of the larynx and trachea.[35] Typically, the pharynx or upper airway is displaced anteriorly by more than half the width of the 4th cervical vertebral body.

Treatment / Management

The goals of treating bacterial pharyngitis are to relieve symptoms and prevent complications. Healthcare professionals do not treat the infection empirically but use the appropriate antibiotics after confirming the infection. Patients should also get adequate rest and fluids and eat a soft diet, taking nonsteroidal anti-inflammatory drugs (NSAIDs) for fever and pain relief. Studies reveal that NSAIDs are more effective than acetaminophen for symptom control.[36]

Group A β-hemolytic Streptococcus

The first-line treatment for children and adults with GABS is oral penicillin V. Amoxicillin is an acceptable alternative, and children may prefer it due to its taste. Penicillin is the only studied antibiotic shown to reduce the rates of acute rheumatic fever, and no documented cases of penicillin resistance exist. Patients with a history of acute rheumatic fever who are not on antibiotic prophylaxis receive oral penicillin V, amoxicillin, or a single dose of intramuscular penicillin G benzathine.[37] The recommended doses are stated below.

• Adults: Oral penicillin V 500 mg 2 to 3 times/d for 10 days, oral amoxicillin 500 mg twice/d for 10 days, or intramuscular (IM) penicillin G benzathine 1.2 million U once
• Children:
  • Oral penicillin V 250 mg 2 to 3 times/d for 10 days in patients weighing 27 kg or less
  • Oral penicillin V 500 mg 2 to 3 times/d for 10 days in patients weighing more than 27 kg
  • Oral amoxicillin 50 mg/kg/d to a maximum of 1000 mg/d for 10 days given daily or in 2 divided doses
  • Penicillin G benzathine 600,000 units IM as a single dose in patients weighing 27 kg or less
  • Penicillin G benzathine 1.2 million units IM as a single dose in patients weighing more than 27 kg

Despite symptom improvement within a few days, eradication from the oropharynx is more effective with a 10-day treatment compared to 5 to 7 days of use. Alternatives for patients who are allergic or unable to tolerate penicillin include cephalosporins, clindamycin, and macrolides. Cephalosporins are suitable in cases of mild penicillin allergy not mediated by immunoglobulin E or penicillin unavailability. Using a narrow-spectrum cephalosporin, such as cephalexin, helps avoid resistance. Azithromycin or clarithromycin is recommended in cases of severe penicillin allergy. The recommended doses are stated below.

• Adults:
  • Oral azithromycin 500 mg/d for 3 days 
  • Oral clarithromycin 250 mg twice/d for 10 days 
  • Oral clindamycin 300 mg 3 times/d for 10 days
  • Oral cephalexin 500 mg twice/d for 10 days
  • Oral cefuroxime 250 mg twice/d for 10 days
• Children:
  • Oral azithromycin 12 mg/kg/d maximum 500 mg/d for 3 days 
  • Oral clarithromycin 7.5 mg/kg/dose twice/d to a maximum of 250 mg per dose for 10 days
  • Oral clindamycin 7 mg/kg/dose 3 times/d to a maximum of 300 mg per dose for 10 days
  • Oral cephalexin 40 mg/kg/d divided twice daily for 10 days to a maximum of 500 mg/dose
  • Oral cefuroxime 10 mg/kg/dose twice/d to a maximum of 250 mg/dose for 10 days 

The macrolides azithromycin and clarithromycin have an increasing resistance rate and are associated with gastrointestinal symptoms and prolongation of the corrected QT interval, which may lead to torsades de pointes. Clindamycin also exhibits increasing resistance rates, and patients taking this medication often experience gastrointestinal adverse effects. The cephalosporins encompass a broader spectrum than penicillin and pose a more significant potential to create antibiotic resistance. Patients can return to work, school, or daycare 24 hours after starting antibiotics.

Other Bacterial Infections

Clinicians should treat pharyngeal gonorrhea or chlamydia infections the same way as a genital infection, with consideration for gonorrhea and chlamydia cotreatment. Gonorrhea therapeutic guidelines from the United States Centers for Disease Control and Prevention (CDC) include the following:

• For individuals who weigh less than 150 kg, ceftriaxone 500 mg IM in a single dose
• For individuals weighing 150 kg or more, ceftriaxone 1 g IM in a single dose [38]

If concurrent NAAT testing for chlamydia is not performed, nonpregnant individuals should be treated with doxycycline 100 mg twice daily for 7 days. Azithromycin 1 g orally as a single dose or oral levofloxacin 500 mg/d may serve as an alternative to doxycycline for the treatment of chlamydia.  

Clinicians should report documented cases of diphtheria to the CDC. Treatment involves airway protection and management with a low threshold for intubation by a clinician experienced in obtaining and maintaining a challenging airway. Erythromycin or penicillin is the first-line antibiotic treatment. Antitoxin, obtained from the CDC, can reduce mortality from 7% to less than 1%.[39] Patients should be placed on respiratory droplet and contact isolation until therapy is complete, and 2 consecutive cultures taken from the nose and throat 24 hours apart both yield negative results.[40](B3)

Local infectious complications of acute pharyngitis, such as a peritonsillar abscess, should be managed in a hospital setting, where clinicians can intervene with appropriate surgical and specialist support. Patients with a peritonsillar abscess warrant antimicrobials, surgical drainage, and supportive care. More studies are needed before clinicians determine glucocorticoids' benefits in managing a peritonsillar abscess. Individuals with cellulitis can receive antimicrobials and supportive care alone. Patients with necrotizing fasciitis require immediate surgical exploration, debridement, and antimicrobials. In addition, individuals who develop toxic shock syndrome, marked by shock and multiorgan failure, should receive intravenous immune globulin along with surgical debridement and appropriate antimicrobial therapy.[41][42](A1)

Differential Diagnosis

As noted, most cases of acute pharyngitis are either noninfectious or viral. When evaluating the possibility of bacterial pharyngitis, healthcare professionals should also consider the following diagnoses:

• Seasonal allergies
• Irritant pharyngitis due to gastroesophageal reflux disease or smoking
• Traumatic pharyngitis due to excessive shouting, snoring, or recent endotracheal intubation
• Aphthous ulcers
• Viral pharyngitis due to common viral respiratory pathogens like adenovirus, rhinovirus, or coronavirus
• Viral pharyngitis due to more serious pathogens like infectious mononucleosis or HIV
• Fungal infections such as esophageal candidiasis
• Lymphangitis
• Peritonsillar or retropharyngeal abscess
• Behçet syndrome
• Stevens-Johnson syndrome
• Kawasaki disease
• Foreign bodies lodged in the mucosal folds of the tonsils or pharynx
• Referred pain from otitis media, dental abscess, and cervical adenitis 
• Lemierre syndrome
• Herpetic stomatitis
• Periodic fever with aphthous stomatitis, pharyngitis, and adenitis (PFAPA syndrome)
• Chemical exposure

Careful clinical evaluation and diagnostic testing can guide treatment and improve outcomes.

Prognosis

Most cases of acute bacterial pharyngitis resolve spontaneously within 3 to 5 days without treatment. The exception is untreated pharyngeal gonorrhea, which takes approximately 16 weeks to resolve without treatment.[43] Successful treatment of confirmed GABS pharyngitis with the appropriate antibiotics generally leads to a favorable prognosis, with rare instances of associated complications.[44]

Some patients may experience recurrent infections within a month postantibiotic treatment, often due to nonadherence to treatment or repeated exposure. In such cases, alternative antibiotics, often with broader coverage, such as amoxicillin-clavulanic acid, clindamycin, or intramuscular penicillin G, may be prescribed. Escalation to a 3rd-generation cephalosporin may be necessary if initial treatment involves a 1st-generation cephalosporin. Emphasizing the importance of adherence to treatment and minimizing risks is crucial in managing recurrent infections.

Sexually transmitted pharyngeal infections are easily treated and most commonly asymptomatic. The rare infections of diphtheria, tularemia, and plague are treatable when basic medical resources are available. However, these infections may have a poor prognosis since most cases develop in highly underresourced settings.[45] Diphtheria can have mortality rates in endemic regions, ranging from 3% to 20%, often due to resultant myocarditis or severely inadequate access to care.[46] Similarly, the mortality associated with Y. pestis ranges from less than 15% when treated to 60% to 100% when left untreated.[47]

Complications

Complications of bacterial pharyngitis generally include the following:

• Peritonsillar abscess
• Sinusitis
• Necrotizing fasciitis
• Submandibular abscesss
• Retropharyngeal abscess
• Parapharyngeal space infection
• Suppurative jugular thrombophlebitis or Lemiere syndrome due to bacterial invasion and clot formation of the jugular vein
• Epiglottitis
• Meningitis
• Mastoiditis
• Sepsis
• Pyomyositis
• Clostridioides difficile colitis [48][49]

Physical examination findings of systemic toxicity, midline or unilateral swelling, or bulging of the posterior pharyngeal wall associated with sore throat, difficulty swallowing, and difficulty breathing may signify a retropharyngeal abscess. Trismus, induration, swelling below the mandibular angle, medial pharyngeal wall bulging, and systemic toxicity indicate a parapharyngeal space infection. Patients may also experience facial and cervical swelling and erythema, parotid gland swelling and displacement, and purulent oral discharge since dental abscesses are the most common underlying cause. A peritonsillar abscess manifests as a high fever, odynophagia, unilateral sore throat, and otalgia. Classic signs include a muffled voice, trismus, unilateral deviation of the uvula toward the unaffected side, and soft palate fullness or edema.

Patients with necrotizing fasciitis typically present with pain disproportionate to the examination findings, poorly defined erythema, edema extending beyond the area of erythema, fever, and the presence of skin bullae, necrosis, or ecchymosis. A characteristic finding is a diminished sensation of pain in the affected area. 

As noted above, GABS pharyngitis can lead to suppurative complications, which encompass the extension of infection beyond the oropharynx, as well as nonsuppurative complications. Nonsuppurative complications are immune phenomena and include the following:

• Acute rheumatic fever
• Poststreptococcal reactive arthritis
• Scarlet fever
• Acute glomerulonephritis
• Pediatric autoimmune neuropsychiatric disorder associated with group A streptococci (PANDAS)
• Toxic shock syndrome

The onset of acute rheumatic fever occurs 2 to 4 weeks following GABS infection, and patients may experience arthritis, carditis, chorea, subcutaneous nodules, and erythema marginatum. Most patients present with an acute febrile illness with joint manifestations and, often, carditis. The diagnosis is clinical, based on the presence of major and minor criteria. See StatPearls' companion reference, "Acute Rheumatic Fever," for additional information. The most common long-term outcome is rheumatic heart disease, occurring 10 to 20 years later. See StatPearls' companion reference, "Rheumatic Heart Disease," for additional information regarding the presentation and long-term sequelae of rheumatic heart disease.

Scarlet fever, caused by a delayed-type skin reactivity to an exotoxin produced by the organism, requires previous exposure and presents with 1- to 2-mm papular eruptions with a sandpaper-like feel. See StatPearls' companion reference, "Scarlet Fever," for additional information. PANDAS occurs in a subset of children whose symptoms of obsessive-compulsive disorder, tic disorders, or other neuropsychiatric symptoms like anxiety are exacerbated by GABS infection. PANDAS is a subset of pediatric acute-onset neuropsychiatric syndrome (PANS) thought sometimes to be brought on by various pathogens, including GABS.[50] See StatPearls' additional companion references, "Toxic Shock Syndrome and Poststreptococcal Glomerulonephritis," for further information regarding these nonsuppurative complications of GABS pharyngitis.

Pharyngeal sexually transmitted infections, such as gonorrhea and chlamydia, rarely cause complications, with 0.5% to 3% of all patients infected with N. gonorrhea in any location developing disseminated gonorrhea. Pharyngeal infections are contagious, increasing the risk of infection for sexual partners who can develop symptoms and cause complications like pelvic inflammatory disease, orchitis, and prostatitis.[51]

Patients with diphtheria may experience respiratory compromise through swelling of the upper airway, cardiovascular compromise through toxin-induced myocarditis, renal failure, and local or systemic paralysis due to neurologic toxicity.[52]

Potential complications associated with tularemia are sepsis, renal failure, rhabdomyolysis, and hepatitis. Rarely, F. tularensis infection may cause otitis media and mastoiditis, endocarditis, pericarditis, myocarditis, meningitis, osteomyelitis, peritonitis, granulomatous hepatitis, spontaneous splenic rupture, and aortitis.[53][54] 

Pharyngitis due to Y. pestis hints at a potential site of inoculation and may not represent a typical initial presentation of plague. Patients who do not develop the typical bubos are challenging to diagnose and may develop meningitis, multiorgan failure, and death.[55][56]