AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Background

Pharyngitis is defined as an infection or irritation of the pharynx and/or tonsils. The etiology is usually infectious, with 40-60% of cases being of viral origin and 5-40% of cases being of bacterial origin. Other causes include allergy, trauma, toxins, and neoplasia.

The main ED concerns with pharyngitis are to rule out more serious conditions, such as epiglottitis or peritonsillar abscess, and to diagnose group A beta-hemolytic streptococcal (GABHS) infections. GABHS infections can have serious sequelae and represent approximately 15% of all ED pharyngitis visits.

Pathophysiology

With infectious pharyngitis, bacteria or viruses may directly invade the pharyngeal mucosa, causing a local inflammatory response. Other viruses, such as rhinovirus, can cause irritation of pharyngeal mucosa secondary to nasal secretion.

Streptococcal infections are characterized by local invasion and release of extracellular toxins and proteases. In addition, M protein fragments of certain serotypes of GABHS are similar to myocardial sarcolemma antigens and are linked to rheumatic fever and subsequent heart valve damage. Acute glomerulonephritis may result from antibody-antigen complex deposition in glomeruli.

Frequency

United States

Children experience more than 5 upper respiratory infections (URIs) per year and an average of one streptococcal infection every 4 years. The occurrence in adults is about one half that rate. The most significant bacterial agent causing pharyngitis in both adults and children is GABHS infection (Streptococcus pyogenes), and the most common viruses are rhinovirus and adenovirus. GABHS is most prevalent in late fall through early spring.

International

The incidence of pharyngitis is higher internationally. Antibiotic resistance may be more prevalent in some countries because of overprescription of antibiotics. It should be noted, however, that there has never been a documented case of GABHS resistant to penicillin anywhere in the world.

Mortality/Morbidity

• One in 400 cases of untreated GABHS infections can be expected to result in acute rheumatic fever. This rate is higher in less developed countries and might actually be lower in the Western world.
• Other sequelae of streptococcal pharyngitis include acute glomerulonephritis, peritonsillar abscess, and toxic shock syndrome.
• Mortality from pharyngitis is rare but may result from one of its complications. For the ED physician, airway obstruction is a concern.

Age

Pharyngitis occurs with much greater frequency in the pediatric population. GABHS is also more common in school-aged children. GABHS causes less than 15% of all adult cases of pharyngitis and about 15-30% of pediatric cases. 

• The peak incidence of bacterial and viral pharyngitis occurs in the school-aged child aged 4-7 years.
• Pharyngitis, especially GABHS infection, is rare in children younger than 3 years.
• Mycoplasma pneumoniae, Chlamydia pneumoniae, and Arcanobacterium haemolyticus peak as causative agents in people in the teen years through the young adulthood years.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

History

A clinical diagnosis of GABHS infection results in an overestimation of incidence by as much as 80%. Many bacterial and viral cases of pharyngitis can be indistinguishable on clinical grounds. However, the classic presentations are described below.

• GABHS infection is most common in children aged 4-7 year.
• Sudden onset is consistent with a GABHS pharyngitis. Pharyngitis following several days of coughing or rhinorrhea is more consistent with a viral etiology.
• Person has been in contact with others diagnosed with GABHS or rheumatic fever.
• Headache is consistent with GABHS or Mycoplasma infection.
• Cough is not usually associated with GABHS infection.
• Vomiting is associated with GABHS infection but may be present in other types of pharyngitis.
• A history of recent orogenital contact suggests the possibility of gonococcal pharyngitis.
• A history of rheumatic fever is important when considering treatment.

Physical

• Airway patency must be assessed and addressed first.
• Temperature
• • Fever is usually absent or low-grade in viral pharyngitis, but fever is not reliable to differentiate viral or bacterial etiologies.
  • Temperature can be as high as 106°F with coxsackievirus A, coxsackievirus B, herpes simplex, GABHS infection, human immunodeficiency virus 1 (HIV-1), infectious mononucleosis, and cytomegalovirus (CMV).
• Hydration status: Oral intake usually is compromised because of odynophagia; therefore, various degrees of dehydration result.
• Head, ears, eyes, nose, and throat (HEENT)
• • Conjunctivitis may be seen in association with adenovirus.
  • Scleral icterus may be seen with infectious mononucleosis.
  • Rhinorrhea usually is associated with a viral cause.
  • Tonsillopharyngeal/palatal petechiae are seen in GABHS infections and infectious mononucleosis.
  • A tonsillopharyngeal exudate may be seen in streptococcal infectious mononucleosis and occasionally in M pneumoniae, C pneumoniae, A haemolyticus, adenovirus, and herpesvirus infections. Therefore, exudate does not differentiate viral and bacterial causes.
  • Oropharyngeal vesicular lesions are seen in coxsackievirus and herpesvirus. Concomitant vesicles on the hands and feet are associated with coxsackievirus (hand-foot-and-mouth disease).
• Lymphadenopathy: Tender anterior cervical nodes are consistent with streptococcal infection, while generalized adenopathy is consistent with infectious mononucleosis or the acute lymphoglandular syndrome of HIV infection.
• Cardiovascular: Murmurs should be documented in an acute episode of pharyngitis to monitor for potential rheumatic fever.
• Pulmonary: Pharyngitis and lower respiratory tract infections are more consistent with M pneumoniae or C pneumoniae, particularly when a persistent nonproductive cough is present.
• Abdomen: Hepatosplenomegaly can be found in infectious mononucleosis infection.
• Skin
• • A sandpapery scarlatiniform rash is seen in GABHS infection (see Scarlet Fever).
  • Maculopapular rashes are seen with various viral infections and with infectious mononucleosis empirically treated with penicillin.

Causes

• Bacterial pharyngitis
• • Group A beta-hemolytic streptococci (15% of all pharyngitis)
  • • The classic clinical picture includes a fever, temperature of greater than 101.5°F, tonsillopharyngeal erythema and exudate, swollen tender anterior cervical adenopathy, headache, emesis in children, palatal petechiae, midwinter to early spring season, and absent cough or rhinorrhea.
    • A scarlatiniform rash also is associated with GABHS infection (scarlet fever), ie, a sandpaperlike erythematous rash over the trunk and extremities with circumoral pallor and a strawberry tongue.
  • Group C, G, and F streptococci (10%) may be indistinguishable clinically from GABHS infection. Acute glomerulonephritis is an extremely unusual complication of group C streptococcal pharyngitis, but a relationship between group G streptococcal pharyngitis and acute glomerulonephritis has not be established. Acute rheumatic fever has not been described as a complication of either. They may be associated with food-borne outbreaks. Group C streptococci have been reported to cause meningitis, endocarditis, and subdural empyemas.
  • Arcanobacterium (Corynebacterium) haemolyticus (5%) is more common in young adults and is very similar to GABHS infection, including a similar scarlatiniform rash. Patients often have a cough. Occasional outbreaks have been reported.
  • M pneumoniae in young adults presents with headache, pharyngitis, and lower respiratory symptoms. Approximately 75% of patients have a cough, which is distinctive from GABHS infection.
  • C pneumoniae (5%) has a clinical picture similar to that of M pneumoniae. Pharyngitis usually precedes the pulmonary infection by about 1-3 weeks.
  • Neisseria gonorrhoeae is a rare cause of pharyngitis. A careful history is important since infection usually follows orogenital contact. It may be associated with severe systemic infection.
  • Corynebacterium diphtheriae is rare in the United States. A foul smelling gray-white pharyngeal membrane may result in airway obstruction.
  • Unusual bacteria that could present with pharyngitis include Borrelia species, Francisella tularensis, Yersinia species, and Corynebacterium ulcerans.
• Viral pharyngitis
• • Adenovirus (5%): The distinguishing feature of an adenovirus infection is conjunctivitis associated with pharyngitis (pharyngoconjunctival fever). It is the most common etiology in children younger than 3 years.
  • Herpes simplex (5%): Vesicular lesions (herpangina), especially in young children, are the hallmark. In older patients, pharyngitis may be indistinguishable from GABHS infection.
  • Coxsackieviruses A and B (5%): These infections present similarly to herpes simplex, and vesicles may be present. If vesicles are whitish and nodular, it is known as lymphonodular pharyngitis. Coxsackievirus A16 may cause hand-foot-and-mouth disease, which presents with 4- to 8-mm oropharyngeal ulcers and vesicles on the hands and feet, and, occasionally, on the buttocks. The oropharyngeal ulcers and vesicles resolve within 1 week.
  • Epstein-Barr virus (EBV): Clinically known as infectious mononucleosis, it is extremely difficult to distinguish from GABHS infection. Exudative pharyngitis is prominent. Distinctive features include retrocervical or generalized adenopathy and hepatosplenomegaly. Atypical lymphocytes can be seen on peripheral blood smear. Viral cultures from washings are about 20% sensitive in adults.
  • CMV: Presentation of CMV is similar to the presentation of infectious mononucleosis. Patients tend to be older, are sexually active, and have higher fever and more malaise. Pharyngitis may not be a prominent complaint.
  • HIV-1: This is associated with pharyngeal edema and erythema, common aphthous ulcers, and a rarity of exudates. Fever, myalgia, and lymphadenopathy also are found.
• Other causes of pharyngitis
• • Oral thrush is due to candidal species, usually in patients who are immunocompromised. It may be common in young children and presents with whitish plaques in the oropharynx.
  • Other causes include dry air, allergy/postnasal drip, chemical injury, gastroesophageal reflux disease (GERD), smoking, neoplasia, and endotracheal intubation.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Other Problems to be Considered

Allergic rhinitis with postnasal drip
Airway obstruction
Head and neck neoplasias
Gastroesophageal reflux disease (GERD)
Peritonsillar cellulitis

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Lab Studies

• GABHS rapid antigen detection test
• • This is the preferred method for diagnosing GABHS infection in the emergency department because of difficulties with culture follow-up.
  • Since rapid antigen testing has become very sensitive, some practice not sending a throat culture for negative antigen tests.
  • Rapid antigen detection is not sensitive for group C and G streptococci or other bacterial pathogens.
• Throat culture
• • This is the criterion standard for diagnosis of GABHS infection (90-99% sensitive). Although less expensive than the rapid antigen detection test, it might not be the best test to use in the emergency department because of difficulty with follow-up. 
  • Positive cultures are clinically important only in patients with a related clinical illness less than 10 days old.
• Antistreptolysin-O (ASO) is a highly sensitive test, but it is not practical in the emergency department because of the need for acute and convalescent titers.
• Mono spot is up to 95% sensitive in children (less than 60% sensitivity in infants).
• Peripheral smear may show atypical lymphocytes in infectious mononucleosis.
• Perform gonococcal culture, as indicated by history.
• Routine laboratory tests usually are not available for A hemolyticus, M pneumoniae, or C pneumoniae.
• Fluorescent monoclonal antibody test exists for C pneumoniae.
• A complete blood count (CBC), erythrocyte sedimentation rate (ESR), and C-reactive protein have a low predictive value and usually are not indicated.

Imaging Studies

• Imaging studies generally are not indicated for uncomplicated viral or streptococcal pharyngitis.
• Lateral neck film should be taken in patients with suspected epiglottitis or airway compromise.
• Soft tissue neck CT should be used if concern for abscess or deep-space infection exists.
• A chest radiograph can elucidate pneumonia in M pneumoniae or C pneumoniae infection or in other clinically suspected lower respiratory infection.

Procedures

• The procedure for a throat swab is to vigorously rub a dry swab over the posterior pharynx and both tonsils, obtaining a sample of exudate. If any exudate is obtained, then transport it dry (not in a liquid medium).

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Prehospital Care

• Prehospital care usually is not necessary for uncomplicated pharyngitis unless airway compromise is an issue.
• Intubation should not be attempted unless the patient stops breathing spontaneously.

Emergency Department Care

• Assess and secure the airway, if necessary.
• Assess the patient for signs of toxicity, epiglottitis, or oropharyngeal abscess.
• Evaluate the hydration status because severe pharyngitis limits oral intake.
• Appropriate measures to rehydrate should be initiated, including intravenous hydration.
• Assess for GABHS infection if clinically suspected. A suggested algorithm as is follows.
• • In general, patients should not be treated without a positive culture or positive rapid antigen detection test result because of increasing antibiotic resistance. The Centers for Disease Control and Prevention (CDC), the American Academy of Family Physicians (AAFP), and the American College of Physicians—American Society of Internal Medicine (ACP-ASIM) recommend the use of a clinical algorithm without microbiologic confirmation to diagnose GABHS in adults only. Guidelines from the Infectious Diseases Society of America (IDSA), American Academy of Pediatrics (AAP), and the American Heart Association state that microbiologic confirmation (via a rapid antigen test or culture) is required for the diagnosis of GABHS.
  • Perform rapid antigen detection test if GABHS is clinically suspected based on history and physical examination. If positive, begin antibiotic therapy. Testing does not usually need to be performed on patients with acute pharyngitis whose clinical and epidemiologic features do not suggest GABHS as the etiology.
  • Household contacts of patients with GABHS infection or scarlet fever should be treated for a full 10 days, even without testing if they have symptoms consistent with GABHS.
  • If clinically doubtful or the above criteria are not met, it is best to await rapid streptococcal or culture results to initiate antibiotic therapy.

Consultations

With a few exceptions, uncomplicated cases of pharyngitis should not require a consultation. Infectious disease specialists should be consulted in the case of unusual presentation or in the case of a patient who is immunocompromised.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

GABHS pharyngitis is usually a self-limited disease, and most signs and symptoms resolve spontaneously in 3-4 days. If administered early, antibiotics can shorten the duration of the illness by up to 1 day, but the main reason they are given is for prevention of acute rheumatic fever. Steroids may be used for airway compromise and symptomatic relief. Antifungals and antivirals are used in certain cases.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Antibiotics are indicated for clinically suspected and culture-verified GABHS infection. They are effective in preventing rheumatic fever if given within 9 days of the onset of pharyngitis. Of note, some experts question the use of antibiotics for the treatment of GABHS infection in the Western world because of the low prevalence of rheumatic fever. Some studies suggest the risk of a serious adverse reaction to an antibiotic is close to the risk of acquiring rheumatic fever. For now, most experts still recommend treatment with antibiotics. Some support the use of cephalosporins instead of penicillin as first-line therapy for GABHS. They cite literature that shows greater eradication of the bacteria in the pharynx after treatment with a cephalosporin. No evidence suggests that this is clinically significant, and most experts still believe that penicillin is still the drug of choice for GABHS in the United States. There has never been a clinical isolate of GABHS documented to be resistant to penicillin anywhere in the world.

Drug Name	Penicillin VK (Beepen-VK)
Description	Inhibits the biosynthesis of cell wall mucopeptide. Bactericidal against sensitive organisms when adequate concentrations are reached. Most effective during the stage of active multiplication. Inadequate concentrations may produce only bacteriostatic effects. Poor patient compliance due to dosing frequency and duration plagues this drug regimen. However, tid dosing is shown in some studies to be as effective as qid dosing. For recurrent streptococcal infections, a combination of penicillin VK and rifampin may be used. Rifampicin, 20 mg/kg/d for 4 d, is added to the standard 10-d treatment with penicillin.
Adult Dose	500 mg PO bid for 10 d
Pediatric Dose	250 mg PO bid/tid for 10 d
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase effectiveness by decreasing clearance; tetracyclines are bacteriostatic, causing a decrease in the effectiveness of penicillins when administered concurrently
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Caution in renal impairment and seizure disorder

Drug Name	Amoxicillin (Amoxil, Biomox, Trimox)
Description	Interferes with synthesis of cell wall mucopeptides during active multiplication resulting in bactericidal activity against susceptible bacteria. Associated with higher incidence of rash. No advantage over oral penicillin, but sometimes more acceptable to children because of taste. Some studies suggest that once-daily dosing of amoxicillin is adequate therapy for GABHS, but further studies are needed to validate this treatment regimen.
Adult Dose	500 mg PO bid for 10 d
Pediatric Dose	50 mg/kg/d PO divided bid for 10 d
Contraindications	Documented hypersensitivity
Interactions	Reduces the efficacy of oral contraceptives
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Adjust dose in renal impairment

Drug Name	Erythromycin (EES, Erythrocin, Ery-Tab)
Description	Interferes with synthesis of cell wall mucopeptides during active multiplication resulting in bactericidal activity against susceptible bacteria (eg, M pneumoniae, C pneumoniae, A haemolyticus), which generally are not sensitive to penicillin. Indicated for patients allergic to penicillin. GABHS resistance is generally thought to be less than 5% in the United States, but more recent studies show resistance rates of up to 30%.
Adult Dose	500 mg PO qid for 10 d A haemolyticus: 250 mg PO qid for 10 d if resistant to penicillin
Pediatric Dose	40-50 mg/kg/d PO divided qid for 10 d; not to exceed 2 g/d
Contraindications	Documented hypersensitivity; hepatic impairment
Interactions	Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI side effects are common (give doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur

Drug Name	Azithromycin (Zithromax)
Description	This antibiotic has a higher cost but has a slightly higher effectiveness than erythromycin. Shorter course and one-a-day dosing make this a good alternative for patients who are sensitive to penicillin.
Adult Dose	500 mg PO qd for 5 d
Pediatric Dose	12 mg/kg/d PO qd for 5 d; not to exceed 500 mg per dose
Contraindications	Documented hypersensitivity; hepatic impairment; do not administer with pimozide
Interactions	May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Site reactions can occur with IV route; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in patients who are hospitalized or debilitated and in geriatric patients

Drug Name	Cephalexin (Keflex)
Description	First-generation cephalosporin arrests bacterial growth by inhibiting bacterial cell wall synthesis. Bactericidal activity against rapidly growing organisms. Primary activity against skin flora. Used for skin infections or prophylaxis in minor procedures. At least as effective as erythromycin in eradicating GABHS infection.
Adult Dose	250-500 mg PO q6h for 10 d
Pediatric Dose	50 mg/kg/d PO q6h for 10 d; not to exceed 3 g/d
Contraindications	Documented hypersensitivity
Interactions	Coadministration with aminoglycosides increases nephrotoxic potential
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Administer half dose if creatinine clearance is 10-30 mL/min and one fourth dose if <10 mL/min; fungal and microorganism overgrowth may occur with prolonged therapy

Drug Name	Ceftriaxone (Rocephin)
Description	Third-generation cephalosporin with broad-spectrum gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins. Indicated for cases of gonococcal pharyngitis. Dosing is different for neonatal gonorrhea.
Adult Dose	250 mg IM once
Pediatric Dose	25-50 mg/kg IM once, not to exceed 250 mg
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase ceftriaxone levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Adjust dose in renal impairment; caution in breastfeeding women and in patients allergic to penicillin

Drug Name	Clindamycin (Cleocin)
Description	Semisynthetic antibiotic produced by 7(S)-chloro-substitution of 7(R)-hydroxyl group of parent compound lincomycin. Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Widely distributes in the body without penetration of CNS. Protein bound and excreted by the liver and kidneys. Used for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). More effective than penicillin in eliminating chronic streptococcal carriage. Recommended for treatment of symptomatic people with multiple, recurrent episodes of GABHS pharyngitis confirmed by rapid antigen testing or culture.
Adult Dose	600 mg PO divided bid/qid for 10 d
Pediatric Dose	20-30 mg/kg PO divided tid for 10 d not to exceed 300 mg/dose
Contraindications	Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment; antibiotic-associated colitis
Interactions	Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects of clindamycin; antidiarrheals may delay absorption of clindamycin
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis by allowing overgrowth of Clostridium difficile

Drug Category: Corticosteroids

The role of steroids in acute pharyngitis remains controversial. Steroids are used in cases of airway obstruction. They have been shown in several studies to reduce clinical symptoms and to shorten the clinical course. Steroids are useful in thrombocytopenia or hemolytic anemia induced by EBV in infectious mononucleosis.

Drug Name	Prednisone (Deltasone, Orasone, Sterapred)
Description	May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Inactive and must be metabolized to the active metabolite prednisolone. The conversion may be impaired in patients with liver disease.
Adult Dose	5-60 mg/d PO qd or divided bid/qid; taper over 2 wk as symptoms resolve
Pediatric Dose	4-5 mg/m2/d PO; alternatively, 0.05-2 mg/kg PO divided bid/qid; taper over 2 wk as symptoms resolve
Contraindications	Documented hypersensitivity; viral, fungal, tubercular skin, and connective tissue infections; peptic ulcer disease; hepatic dysfunction; GI bleeding or ulceration
Interactions	Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Drug Category: Antifungals

These agents are indicated for cases of pharyngitis associated with oral thrush.

Drug Name	Fluconazole (Diflucan)
Description	Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal CYP-450 and sterol C-14 alpha-demethylation.
Adult Dose	200 mg PO once, then 100 mg qd for 14 d
Pediatric Dose	3-6 mg/kg PO qd for 14-28 d or 6-12 mg/kg qd, depending on severity of infection
Contraindications	Documented hypersensitivity
Interactions	Levels may increase with hydrochlorothiazide; fluconazole levels may decrease with chronic coadministration of rifampin; coadministration of fluconazole may decrease phenytoin concentrations; may increase concentrations of theophylline, tolbutamide, glyburide, and glipizide; effects of anticoagulants may increase with fluconazole coadministration; increases in cyclosporine concentrations may occur when administered concurrently
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Closely monitor if rashes develop, and discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death) when taken with underlying medical conditions (eg, AIDS, malignancy) and while taking multiple concomitant medications; not recommended for breastfeeding mothers

Drug Category: Antivirals

In general, these agents have not been shown to have clinical benefit in viral pharyngitis. However, in patients who are immunocompromised, a role does exist. In severe cases of herpes simplex pharyngitis and for immunocompromised patients, acyclovir, famciclovir, and valacyclovir are recommended. In CMV infections in immunocompromised patients, foscarnet or ganciclovir are recommended. Consultation with an infectious disease specialist is recommended before using one of these agents.

Drug Name	Famciclovir (Famvir)
Description	Prodrug that when biotransformed into active metabolite, penciclovir, may inhibit viral DNA synthesis/replication.
Adult Dose	Not established Suggested dosing: 500 mg PO q8h for 7 d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Coadministration of probenecid or cimetidine may increase toxicity; coadministration increases bioavailability of digoxin
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Caution in renal failure or coadministration of nephrotoxic drugs

Drug Name	Ganciclovir (Cytovene, Vitrasert)
Description	An acyclic nucleoside analog of 2'-deoxyguanosine that inhibits replication of herpes viruses both in vitro and in vivo. Levels of ganciclovir-triphosphate are as much as 100-fold greater in CMV-infected cells than in uninfected cells, possibly due to preferential phosphorylation of ganciclovir in virus-infected cells. For patients who experience progression of CMV retinitis while receiving a maintenance treatment with either dosage form of ganciclovir, the re-induction regimen should be administered.
Adult Dose	Not established Suggested dosing: Induction: 5 mg/kg IV over 1 h q12h for 14-21 d (do not use PO ganciclovir for induction treatment) Maintenance PO: 500 mg q4h or 1 g tid for life Maintenance IV: 5 mg/kg qd for 5-7 d/wk
Pediatric Dose	<3 months: Not established >3 months: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Concomitant administration with cytotoxic drugs, such as dapsone, vinblastine, doxorubicin (Adriamycin), pentamidine, flucytosine, vincristine, amphotericin B, trimethoprim/sulfamethoxazole combinations, or other nucleoside analogs, may result in additive toxicity in bone marrow, spermatogonia, and germinal layers of skin and GI mucosa (coadminister only if potential benefits outweigh risks); coadministration with imipenem-cilastatin may cause generalized seizures (use only if potential benefits outweigh risks); serum creatinine level may increase following concurrent use of ganciclovir with either cyclosporine or amphotericin B; in presence of probenecid, ganciclovir renal clearance is reduced; bioavailability may increase when didanosine is administered either 2 h before or simultaneously with ganciclovir; bioavailability of ganciclovir may decrease in presence of zidovudine, while bioavailability of zidovudine is increased in presence of ganciclovir
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Clinical toxicity of ganciclovir includes granulocytopenia, anemia, and thrombocytopenia; because oral ganciclovir is associated with higher rate of CMV retinitis progression compared with IV formulation, use only when benefits outweigh risks (advanced HIV disease); half-life and plasma/serum concentrations of ganciclovir may be increased as a result of reduced renal clearance; dosages >6 mg/kg IV may result in increased toxicity; rapid infusions may result in increased toxicity; initially, reconstituted solutions of IV ganciclovir have a high pH (11); phlebitis or pain may occur at site of IV infusion despite further dilution in IV fluids; administration of ganciclovir should be accompanied by adequate hydration; photosensitization (photoallergy or phototoxicity) may occur

Drug Name	Foscarnet (Foscavir)
Description	Organic analog of inorganic pyrophosphate that inhibits replication of known herpesviruses, including CMV, HSV-1, and HSV-2. Inhibits viral replication at pyrophosphate-binding site on virus-specific DNA polymerases. Poor clinical response or persistent viral excretion during therapy may be due to viral resistance. Patients who can tolerate foscarnet well may benefit from initiation of maintenance treatment at 120 mg/kg/d early in treatment. Individualize dosing based on renal function status. Infuse into veins with adequate blood flow to avoid local irritation. Not to be administered by rapid or bolus IV injection to avoid toxicity.
Adult Dose	Not established Suggested dosing: Induction: 60 mg/kg/dose IV q8h or 100 mg/kg IV q12h for 14-21 d Maintenance: 90-120 mg/kg/d IV as a single infusion for life Acyclovir-resistant induction in HSV infections: 40 mg/kg/dose IV q8-12h for 14-21 d
Pediatric Dose	<12 years: Not established >12 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Coadministration with potentially nephrotoxic drugs (eg, aminoglycosides, amphotericin B, IV pentamidine) may increase nephrotoxicity (do not administer unless potential benefits outweigh risks); coadministration with IV pentamidine may cause hypocalcemia
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	May cause decline in renal function; for correct dosing, obtain 24-h serum creatinine level at baseline, and continue to monitor (discontinue if serum creatinine level <0.4 mL/min/kg); hydration may reduce nephrotoxicity; carefully monitor electrolytes (eg, calcium, magnesium); assess for electrolyte and mineral level abnormalities if mild perioral numbness, paresthesias symptoms, or seizures; granulocytopenia and anemia may occur (regularly monitor CBC)

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Further Inpatient Care

• Inpatient care usually is not indicated except in cases such as epiglottitis, severe dehydration, deep-space infection, other airway compromise, or diphtheria.

Further Outpatient Care

• Follow-up for GABHS pharyngitis
• • A standardized protocol needs to be established at each institution or ED to ensure follow-up for patients with pending throat cultures. Ensuring follow-up for patients is particularly challenging with unreliable patients and with a shift-dependent ED practice.
  • Whether or not they are given antibiotics, patients diagnosed with pharyngitis should follow up if symptoms do not improve within 72 hours.
  • Routine posttreatment throat cultures are unnecessary and may remain positive for several weeks.
  • A follow-up culture should be taken if history or evidence of rheumatic fever or if symptoms are consistent with a relapse.
• Patients with infectious mononucleosis should be instructed to follow up with their physician in 1 week. These patients should also be advised to avoid contact sports.
• Viral pharyngitis generally requires no specific follow-up unless immunosuppression is suspected or symptoms worsen.
• Patients with suspected malignancy should be referred to an otolaryngologist for follow-up.

Transfer

• Transfer usually is not necessary for simple acute pharyngitis.
• The airway should be evaluated and endotracheal intubation should be performed prior to transfer if a high probability of compromise exists during transfer.

Deterrence/Prevention

• Throat cultures should be obtained on close contacts of patients with a history of a nonsuppurative complication of a streptococcal infection or if recurrent outbreaks of GABHS pharyngitis occur.
• Diphtheria immunization is highly effective and recommended for nonimmunized patients to reduce potential morbidity and mortality of the disease.

Complications

• General complications of pharyngitis (mainly seen in cases of bacterial pharyngitis) include sinusitis, otitis media, epiglottitis, mastoiditis, and pneumonia.
• • Recurrence is usually due to patient noncompliance but may be due to bacterial resistance/treatment failure or a new exposure.
  • Suppurative complications of bacterial pharyngitis result from spread of infection from pharyngeal mucosa via hematogenous, lymphatic, or direct extension (more common with GABHS); peritonsillar abscess; retropharyngeal abscess; or suppurative cervical lymphadenitis.
• In addition to the above general complications, nonsuppurative complications (3% incidence) specific to GABHS infection include acute rheumatic fever (3-5 wk postinfection), poststreptococcal glomerulonephritis, and toxic shock syndrome.
• Complications of infectious mononucleosis include splenic rupture (contact sports should be avoided for 6 wk), hepatitis, Guillain-Barré syndrome, encephalitis, hemolytic anemia, agranulocytosis, myocarditis, B-cell lymphoma, and nasopharyngeal carcinoma. Use of penicillin in cases of infectious mononucleosis results in near 100% incidence of rash.

Prognosis

• Most cases of pharyngitis resolve spontaneously within 10 days, but it is important for the clinician to be aware of potential complications listed above.
• Treatment failures are frequent and are attributed mainly to poor compliance, antibiotic resistance, untreated close contacts, carrier states, and antibiotic-related or copathogenic suppression of host immunity and necessary flora.
• Patients should expect improvement in symptoms in penicillin-sensitive streptococcal pharyngitis within 24 hours of initiation of treatment. Contagious and often the febrile periods also are reduced to 1 day.
• With erythromycin therapy, patients should expect improvement in 72 hours. The incidence of streptococcal resistance to erythromycin may exceed 30%. Therefore, patients on erythromycin therapy should be more closely monitored for treatment failure.

Patient Education

• Patients must be instructed to complete the full course of antibiotic therapy, as improvement may occur rapidly.
• The risk of recurrence is high and has been established to be higher in patients who complete a 7-day, as opposed to 10-day, course of antibiotics.
• Patients should be instructed to follow up when indicated (see Further Outpatient Care).
• Patients with infectious mononucleosis should be instructed to avoid contact sports for a period of 6 weeks because of the possibility of splenic rupture.
• Patients should be educated about symptomatic treatment of pharyngitis.
• • Ibuprofen or acetaminophen is recommended for analgesia.
  • Saltwater gargle, warm liquids, and rest may be helpful in relieving symptoms.
• For excellent patient education resources, visit eMedicine's Bacterial and Viral Infections Center. Also, see eMedicine's patient education articles Sore Throat and Mononucleosis.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical/Legal Pitfalls

• Medical/legal issues usually are not applicable in uncomplicated pharyngitis.
• Chronic pharyngitis should elicit a search for the possibility of malignancy, particularly in patients with predisposing factors such as age and tobacco or alcohol use.
• Be aware of the signs of immunosuppression.
• Carefully document follow-up instructions, signs and symptoms of recurrence, and all complications.

Special Concerns

• Pediatric
• • Recurrent streptococcal pharyngitis (6-7 recurrences over 1-2 y) may require tonsillectomy or special antibiotic therapy.
  • Clindamycin is recommended for recurrent streptococcal infections because of its beta-lactamase stability.
• Indiscriminate use of antibiotics is widespread, erroneous, and detrimental to the patient and the community.
• • Indiscriminate antibiotic use leads to increased bacterial resistance, treatment failures, and increased occurrence of antibiotic side effects. Most experts believe that GABHS pharyngitis should only be treated with antibiotics if a test (rapid antigen or culture) is positive.
  • Patients may seek out unnecessary antibiotic treatment in the future.

ACKNOWLEDGMENTS

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, A Antoine Kazzi, MD, and Jeannine Wills, MD, to the development and writing of this article.

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

• Bisno AL. Acute pharyngitis: etiology and diagnosis. Pediatrics. Jun 1996;97(6 Pt 2):949-54. [Medline].
• Bisno AL, Gerber MA, Gwaltney JM Jr, Kaplan EL, Schwartz RH. Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis. Infectious Diseases Society of America. Clin Infect Dis. Jul 15 2002;35(2):113-25. [Medline].
• Blumer JL, Goldfarb J. Meta-analysis in the evaluation of treatment for streptococcal pharyngitis: a review. Clin Ther. Jul-Aug 1994;16(4):604-20; discussion 603. [Medline].
• Cohen R, Levy C, Doit C, De La Rocque F, Boucherat M, Fitoussi F, et al. Six-day amoxicillin vs. ten-day penicillin V therapy for group A streptococcal tonsillopharyngitis. Pediatr Infect Dis J. Aug 1996;15(8):678-82. [Medline].
• Del Mar CB, Glasziou PP, Spinks AB. Antibiotics for sore throat (Review). The Cochrane Collaboration. 2007;(1):1-41.
• Denny FW Jr. Tonsillopharyngitis 1994. Pediatr Rev. May 1994;15(5):185-91. [Medline].
• Edmond KM, Grimwood K, Carlin JB, Chondros P, Hogg GG, Barnett PL. Streptococcal pharyngitis in a paediatric emergency department. Med J Aust. Oct 21 1996;165(8):420-3. [Medline].
• Gerber MA. Diagnosis and treatment of pharyngitis in children. Pediatr Clin North Am. Jun 2005;52(3):729-47, vi. [Medline].
• Kline JA, Runge JW. Streptococcal pharyngitis: a review of pathophysiology, diagnosis, and management. J Emerg Med. Sep-Oct 1994;12(5):665-80. [Medline].
• Mainous AG 3rd, Zoorob RJ, Kohrs FP, Hagen MD. Streptococcal diagnostic testing and antibiotics prescribed for pediatric tonsillopharyngitis. Pediatr Infect Dis J. Sep 1996;15(9):806-10. [Medline].
• McIsaac WJ, Goel V, Slaughter PM, Parsons GW, Woolnough KV, Weir PT, et al. Reconsidering sore throats. Part I: Problems with current clinical practice. Can Fam Physician. Mar 1997;43:485-93. [Medline].
• Meland E, Digranes A, Skjaerven R. Assessment of clinical features predicting streptococcal pharyngitis. Scand J Infect Dis. 1993;25(2):177-83. [Medline].
• Middleton DB. Pharyngitis. Prim Care. Dec 1996;23(4):719-39. [Medline].
• Pichichero M, Casey J. Comparison of European and U.S. results for cephalosporin versus penicillin treatment of group A streptococcal tonsillopharyngitis. Eur J Clin Microbiol Infect Dis. Jun 2006;25(6):354-64. [Medline].
• Pichichero ME. Group A streptococcal tonsillopharyngitis: cost-effective diagnosis and treatment. Ann Emerg Med. Mar 1995;25(3):390-403. [Medline].
• Pichichero ME. Pathogen shifts and changing cure rates for otitis media and tonsillopharyngitis. Clin Pediatr (Phila). Jul 2006;45(6):493-502. [Medline].
• Pichichero ME. Sore throat after sore throat after sore throat. Are you asking the critical questions?. Postgrad Med. Jan 1997;101(1):205-6, 209-12, 215-8, passim. [Medline].
• Scaglione F, Demartini G, Arcidiacono MM, Pintucci JP. Optimum treatment of streptococcal pharyngitis. Drugs. Jan 1997;53(1):86-97. [Medline].
• Shulman ST. Complications of streptococcal pharyngitis. Pediatr Infect Dis J. Jan 1994;13(1 Suppl 1):S70-4; discussion S78-9. [Medline].
• Smith DS. Current concepts in the management of pharyngitis. Compr Ther. Dec 1996;22(12):806-9. [Medline].
• Talan DA. Infectious disease issues in the emergency department. Clin Infect Dis. Jul 1996;23(1):1-12, quiz 13-4. [Medline].
• Van Howe RS, Kusnier LP 2nd. Diagnosis and management of pharyngitis in a pediatric population based on cost-effectiveness and projected health outcomes. Pediatrics. Mar 2006;117(3):609-19. [Medline].

Article Last Updated: Nov 5, 2007