Bacterial Pharyngitis

Etiology

Acute pharyngitis is quite common in both children and adults, usually arising from non-infectious (i.e., seasonal allergies and acid reflux) or non-bacterial (i.e., viral) causes.[1] However, when the cause is bacterial, pharyngitis is most often caused by group A beta-hemolytic Streptococcus (GABHS), commonly referred to as strep throat.[3] GABHS is transmitted via airborne transmission or ingestion and is associated with acute and delayed complications, which will be described later in the article.

Other bacteria may also cause pharyngitis, including streptococcus groups C and G, but due to the difficulty of distinguishing colonization from infection, it is difficult to quantify the relative rates of these bacterial causes.[4] Sexually transmitted infections, such as Neisseria gonorrhea and Chlamydia trachomatis, should be considered if risk factors are present, though they are typically asymptomatic.[5] Rarer infections, such as Yersinia pestis and Corynebacterium diphtheriae, could be considered if recent exposure to endemic areas is suspected.[6][7]

Epidemiology

Sore throat is an extremely common presenting complaint in providers' offices, emergency departments, and urgent care centers.[8] The complaint is particularly common among pediatric patients, who account for around half of all cases. Among adults, bacterial pharyngitis is less common with age, with most cases occurring in patients less than 40 years old.[9][10] Bacterial causes are dominated by Group A strep infections, again more commonly among children, who are also more likely to suffer from acute and delayed complications of strep infections.[4][11]

The other bacterial causes of sore throat are rarer but are highly associated with risk factors. While gonorrhea and chlamydia are frequently asymptomatic, a pharyngeal STI is present in nearly 10% of those with some risk factors.[5] Further, cases of diphtheria are confined to unvaccinated populations or to regions of the world where the disease remains endemic.[7]

Pathophysiology

In bacterial pharyngitis, bacteria invade the mucosal tissues of the pharynx directly. Extracellular factors such as proteases facilitate the tissue invasion and cause the inflammation that elicits swelling, exudates, fever, and pain with swallowing.[12][13] As it is experienced more broadly, the inflammation may also contribute to symptoms of otitis and sinusitis, even when those areas have not been infected with the same bacteria.

Streptococcus specifically expresses a hyaluronic acid capsule that matches host tissue and prevents the typical immune response, making treatment particularly dependent on antibiotics.[14] While untreated bacterial infections can penetrate more deeply, leading to more serious infections like cellulitis, abscess, or bacteremia, this is much less likely than prior to common antibacterial treatment.

Some bacteria produce exotoxins, which can intensify the local tissue destruction or cause severe systemic symptoms. A local exotoxin can cause diphtheria’s pathognomonic pseudomembrane, and systemic toxins can cause scarlet fever and the rare toxic shock syndrome associated with streptococcus.[15][16]

Likely due to molecular similarities between streptococcus and host tissues, there is an additional risk for noninfectious complications of this pharyngitis. Rheumatic fever and glomerulonephritis can follow a streptococcal infection, likely resulting from molecular mimicry and multi-factorial autoimmune reactions, respectively.[15]

History and Physical

As with most medical conditions, the diagnosis and management of bacterial pharyngitis depend on collecting an effective history and performing a directed physical exam. Bacterial pharyngitis is most commonly acute in onset with a relatively isolated severe sore throat, potentially with associated symptoms like the scarlatiniform rash or abdominal pain.[3][4] Providers should collect information about associated symptoms, time course, previous history, and risk factors. Additional upper respiratory symptoms, such as congestion, cough, and eye irritation, suggest viral infections or seasonal allergies as more likely etiologies.[2] Seasonally recurrent or persistent symptoms with no fever favor allergic etiologies. History of acid reflux, positional exacerbation, and association with recent irritant foods, caffeine, or alcohol favors gastroesophageal reflux disease. Risk factors like high-risk sexual behavior or close family with strep throat may lower the bar for potential testing.

An appropriate physical exam would include assessing vital signs for fever and evidence of clinical instability, evaluating the ears, conjunctiva, and nares for evidence of the symptoms described or alternative explanations for a potential fever. Evaluation of the oropharynx and neck should assess for swelling and exudates of the tonsils and pharynx and lymphadenopathy. Exudates or a pseudomembrane favors a bacterial etiology, as do swollen and tender lymph nodes. More diffuse swelling of the conjunctiva, nasal turbinates, and pharynx, especially associated with post-nasal drip, favor non-bacterial etiologies.[17] Especially in children, a skin exam is appropriate to look for the red, sandpapery rash of scarlet fever or evidence of other exanthems that might indicate an alternative infection.

Evaluation

Diagnosis of bacterial pharyngitis should not be made based solely on clinical exam findings but rather on a combination of an objective clinical exam leading to appropriate laboratory testing.[2][17] Several tools are available to help remove subjectivity from the clinical exam, and a variety of point-of-care and laboratory tests have been developed to confirm clinical indications.

The first developed of the clinal tools was the Centor criteria, the purpose of which is to evaluate the likelihood of a streptococcal infection. Those criteria include tonsillar exudates, fever of more than 100.4 F (38 C), tender anterior cervical lymphadenopathy, and the absence of a cough. Patients with limited Centor criteria (0-1) are unlikely to have a streptococcal infection, and testing is unnecessary. Patients with many of the criteria (3-4) are more likely to have the infection and warrant point-of-care or laboratory testing.[18] The McIsaac criteria modify the original Center criteria to account for age differences by adding a point for patients ages 3 to 14 and subtracting a point for patients 45 and over.[18] The FeverPAIN criteria include fever, tonsillar exudates, severe inflammation, onset within three days, and the absence of cough or coryza. Again, patients with limited criteria (0-1) are unlikely to have strep infections, and those with many criteria (4 or more) are more likely.[19]

A rapid antigen detection test (RADT) is a point of care test used to check for streptococcus in those patients whose infections cannot confidently be attributed to other causes. Its specificity is around 95%, so a positive RADT result requires no further testing. However, it has a sensitivity ranging from 70 to 90%, so, in patients with many indications of bacterial infection, a negative RADT should be confirmed with a traditional throat culture.[20]

A bacterial throat culture is a gold standard for diagnosing a streptococcal infection. Unfortunately, the results are not available for up to a day or two. This is especially problematic in patients for whom follow up is more difficult, such as emergency department patients or those with unstable contact information.

A Nucleic acid amplification test (NAAT) for Neisseria gonorrhea and Chlamydia trachomatis can be used to test for pharyngeal infections. Though it is not FDA-approved, the CDC endorses its use for appropriate screening or diagnosis as it is more sensitive than traditional cultures. While pharyngeal gonorrhea and chlamydia are unlikely to cause symptoms, NAAT swab testing would be appropriate in patients with high-risk or in cases where the sore throat does not respond appropriately to standard treatment.[21]

Blood tests such as leukocyte count and C-reactive protein may also be performed to evaluate a patient's clinical stability or the risk of systemic illness. Anti-streptococcal antibody testing will not help to diagnose acute infections since they are not immediately present and are not reliably persistent.[22]

Imaging is appropriate only in circumstances where the patient demonstrates instability consistent with an abscess or other severe etiology of sore throat, in which case the patient should be transferred to an emergency or inpatient setting.[23]

Even those meeting all criteria for the clinical evaluation tools have only a 50 to 65% chance of having a streptococcal infection. Because of this, the Infectious Disease Society of America recommends not relying on clinical evaluation alone to determine treatment. While past recommendations endorsed the use of empiric antibiotics for patients with high scores, the most recent recommendations, noting the increased prevalence and accuracy of point-of-care testing and potentially limited morbidity of untreated infections, recommend confirming infections before treatment.[2] This recommendation is not universally accepted but can serve to temper the aggressive use of antibiotics without testing.

Treatment / Management

Bacterial pharyngitis should be treated with appropriate antibiotics once the infection has been confirmed. The symptoms for any pharyngitis should be additionally treated with nonsteroidal anti-inflammatory drugs or acetaminophen for antipyresis and analgesia.

For GABHS, the first-line antibiotic treatments are penicillins because they are inexpensive and effective, and no significant antibiotic resistance has been discovered. Penicillin V and amoxicillin are typical. Cephalosporins are also appropriate for patients with a mild penicillin allergy or when penicillin is not available. Treatment with the narrowest possible spectrum cephalosporin is recommended to avoid developing resistance. In patients with a more severe allergy to penicillin, treatment with azithromycin can be appropriate, but macrolide resistance has been increasing. Finally, when resistance to azithromycin is known, clindamycin can be used to treat those with severe penicillin allergies, though it too faces resistance and has higher rates of intolerance due to taste, intestinal side effects and possible opportunistic bacterial infections such as with clostridium difficile.[2][3](A1)

Cases of pharyngeal gonorrhea or chlamydia should be treated as would be genital infections, typically co-treating for both gonorrhea and chlamydia with 250 mg of ceftriaxone intramuscularly and 1000 mg of azithromycin per orally.[21]

Cases of diphtheria should be reported to the CDC and are best treated with antibiotics (erythromycin or penicillin) and antitoxin (available through the CDC). Patients should be placed on respiratory droplets and contact isolation until two consecutive cultures taken 24 hours apart are both negative.[24](B3)

Cases of Yersinia pestis should be treated with appropriate antibiotics (aminoglycosides or tetracyclines, primarily), and patients should be placed on respiratory droplet precautions until cultures are negative and antibiotics have been given for at least 48 hours.[25](B3)

Local infectious complications of acute pharyngitides, such as a peritonsillar abscess, should be managed in a hospital setting, where interventions can be made with appropriate surgical and specialist support, such as availability of rapid intubation if a patient's airway becomes compromised.[23]

Differential Diagnosis

As noted, the majority of cases of acute bacterial pharyngitis are either noninfectious or nonbacterial. When considering the possibility of bacterial pharyngitis, providers should also consider:

• Allergic reaction to environmental factors like pollen, indoor or outdoor pollutants or medications
• Irritant pharyngitis due to gastroesophageal reflux or smoking
• Traumatic pharyngitis due to excessive shouting, snoring, or recent tracheal intubation
• Aphthous ulcers
• Viral pharyngitis due to common viral upper respiratory pathogens like adeno-, rhino-, or coronavirus
• Viral pharyngitis due to more serious pathogens like infectious mononucleosis, pandemic coronavirus or HIV
• Fungal infections such as esophageal candidiasis
• Bacterial complications such as lymphangitis or peritonsillar or retropharyngeal abscess

Prognosis

Most cases of acute bacterial pharyngitis are self-limiting. If GABHS infection is confirmed and treated with an appropriate antibiotic, the prognosis is good. Rarely, a patient may develop one of the complications.[26]Some patients may experience a repeat infection within one month of antibiotic treatment. This is often due to non-compliance with antibiotic medication, though it may result from repeat exposure. If it occurs, the patient can be treated with an alternative antibiotic, often with broader coverage, and the importance of adherence to treatment and avoidance of risks can be emphasized. The most commonly used antibiotics are amoxicillin-clavulanic acid, clindamycin, intramuscular penicillin G. If a first-generation cephalosporin had been used initially, antibiotics are typically escalated to a third-generation cephalosporin.[2]

Sexually transmitted pharyngeal infections are easily treated and most commonly asymptomatic.[21]

The rare infections of diphtheria and Yersinia pestis are quite treatable when basic medical resources are available, though they may be associated with poor prognosis since most cases would develop in highly under-resourced settings.[24][25] In the regions where it occurs, diphtheria could have mortality ranging from 3-20%, often related to resultant myocarditis or severely inadequate access to care.[27] Similarly, the mortality associated with Yersinia pestis ranges from less than 15%, when treated, to 60 to 100% when left untreated.[28]

Complications

Different complications may develop from bacterial pharyngitis, depending on the specific bacterial cause. Generally, a bacterial infection can spread, leading to abscess, cellulitis, lymphadenitis, meningitis, and bacteremia. It will also cause local swelling, which can lead to inflammation due to occlusions, such as sinusitis and otitis media.[12][13]

While streptococcal infections are typically self-limited, it is important to diagnose and treat them with antibiotics since GABHS infections may lead to serious complications. Exotoxins produced by GABHS can produce scarlet fever or toxic shock syndrome. An autoimmune response triggered by a GABHS infection can lead to acute rheumatic fever.[15][16] Though post-streptococcal glomerulonephritis also results from dysfunctional immune response, it is not prevented by appropriate antibiotic treatment.[2]

Pharyngeal sexually transmitted infections, such as gonorrhea and chlamydia, are often asymptomatic and do not typically lead to complications for the host but are contagious, leading to infections for partners that can be symptomatic and can lead to complications such as pelvic inflammatory disease, orchitis, and prostatitis.[29]

Diphtheria's primary pathology arises from toxin production. The toxin produces necrosis and inflammation, can lead to respiratory compromise through swelling of the upper airway, cardiovascular compromise through toxin-induced myocarditis, and local or systemic paralysis through neurologic toxicity.[24][25]

Pharyngitis due to Yersinia pestis represents a potential site of inoculation rather than a typical initial presentation. Plague typically progresses to severe lymphadenitis, followed by potential dissemination.[30]