Medication Summary
GAS 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. [34] This rationale is being questioned by many as the incidence of acute rheumatic fever in the United States is extremely low. In addition, pain medications such as NSAIDs or acetaminophen and steroids can alleviate the symptoms associated with GAS pharyngitis. [35] Antibiotics do not prevent acute glomerulonephritis. Steroids may be used for airway compromise and symptomatic relief. [36] Antifungals and antivirals are used in certain rare cases with specialist consultation.
A randomized, double-blind study by Shephard et al suggested that lozenges containing flurbiprofen 8.75 mg can alleviate moderate to severe pharyngitis symptoms for 3-4 hours, whether or not the patient is suffering from a group A or C streptococcal infection. [37]
A study by Müller et al indicated that a mouth and throat spray containing the osmolyte ectoine is effective against acute pharyngitis and/or laryngitis, demonstrating good to very good tolerability and reducing cervical lymph node swelling to a significantly greater degree than saline lozenges. The prospective, controlled, nonrandomized trial included 95 patients. [38]
A study by Fleming-Dutra et al found that, based on the 2010-2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, pharyngitis was responsible for 43 ambulatory antibiotic prescriptions per 1000 population in the United States, the third highest rate of such prescriptions for a single diagnosis (after sinusitis and suppurative otitis media). [39, 40, 41]
Antibiotics
Class Summary
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 or antigen-verified GAS 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 GAS infection in the Western world because of the low prevalence of rheumatic fever. Some European guidelines for the treatment of pharyngitis only recommend antibiotics for patients with culture-positive GAS pharyngitis who are high-risk for acute rheumatic fever or very ill. [42] One study suggested that observation alone was most cost-effective strategy for GAS pharyngitis in children, and this strategy also had lower morbidity and mortality than antibiotic treatment groups. [43] For now, most experts and guidelines in the United States still recommend treatment with antibiotics. It should be noted, however, that the risk of a serious antibiotic adverse effects is higher than the risk of developing acute rheumatic fever as a consequence of GAS pharyngitis in the United States.
Some support the use of cephalosporins instead of penicillin as first-line therapy for GAS. [44, 45] 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 clinical guidelines still advocate that penicillin is still the drug of choice for GAS in the United States. There has never been a clinical isolate of GAS documented to be resistant to penicillin anywhere in the world. [13] In cases of clinical treatment failure of GAS pharyngitis after penicillin therapy, a cephalosporin or broader-spectrum penicillin (ampicillin-sulbactam) should be considered, but these instances are rare. [31] Cephalosporins should be considered first-line therapy if the patient has a history of recent antibiotic usage, recurrent pharyngitis infection, or if a high failure rate of penicillin is documented in the community. [46]
Macrolide resistance of GAS varies widely from year to year and among different parts of the world from 5% to 97%. Patients should only be treated with a macrolide if a penicillin or cephalosporin type drug is not an option. If a macrolide is used to treat GAS, patients should be followed closely for treatment failure, as very rare case reports describe acute rheumatic fever after GAS treatment with macrolides. [47]
Some controversy exists regarding the treatment of carriers of GAS. These are patients who have a positive rapid antigen or culture without symptoms of pharyngitis. It is believed that this carrier state does not lead to acute rheumatic fever or other complications of GAS pharyngitis. Most carriers should not be treated; however, treatment should be considered in carriers with the following characteristics:
- Recurrent pharyngitis without cough or congestion
- Acute rheumatic fever (ARF) or poststreptococcal glomerulonephritis outbreaks
- GAS pharyngitis in closed community
- Family history of ARF
- Multiple documented GAS pharyngitis episodes within a family over several weeks despite therapy
If carriers are treated, clindamycin for 10 days or IM penicillin plus 4 days of rifampin are recommended treatment options. [48]
While some literature exists to support the use of a shorter course of antibiotic therapy for GAS pharyngitis, most international guidelines still recommend a 10-day course for most antibiotics. [49]
Penicillin G benzathine (Bicillin LA)
Inhibits biosynthesis of cell wall mucopeptide. Bactericidal against sensitive organisms when adequate concentrations reached, and most effective during stage of active multiplication. Inadequate concentrations may produce only bacteriostatic effects. Still is drug of choice in GAS pharyngitis because of its narrow spectrum of activity, low cost, and proven safety track record. IM penicillin is drug of choice in patients where compliance is an issue because of single dose.
Penicillin VK (Beepen-VK)
Inhibits the biosynthesis of cell wall mucopeptide. Bactericidal against sensitive organisms when adequate concentrations are reached. Most effective during 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.
Amoxicillin (Amoxil, Biomox, Trimox)
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.
Cephalexin (Keflex)
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. Choice for patients who are sensitive for penicillin.
Azithromycin (Zithromax)
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 allergic to penicillin.
Erythromycin (EES, Erythrocin, Ery-Tab)
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%.
Clindamycin (Cleocin)
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.
Ceftriaxone (Rocephin)
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.
Corticosteroids
Class Summary
Steroids have been shown to improve clinical symptoms in patients with pharyngitis, particularly in patients with severe or exudative pharyngitis. [50] Steroids are also used in cases of airway obstruction. They have been shown in several studies to reduce clinical symptoms and to shorten the clinical course. [51, 52] They should be used selectively for patients with significant swelling or odynophagia. [36, 52]
Dexamethasone (Decadron)
Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability. For pharyngitis, steroids must be administered in conjunction with antibiotics. Provides symptomatic relief for severe pharyngitis. A one-time IM dose is convenient and avoids compliance issues. Betamethasone is an alternative to dexamethasone.
Prednisone (Deltasone, Orasone, Sterapred)
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.
Antifungals
Class Summary
These agents are indicated for cases of pharyngitis associated with oral thrush.
Nystatin (Mycostatin)
Fungicidal and fungistatic antibiotic obtained from Streptomyces noursei. Effective against various yeasts and yeastlike fungi. Changes permeability of fungal cell membrane after binding to cell membrane sterols, causing cellular contents to leak. Treatment should continue until 48 h after disappearance of symptoms.
Fluconazole (Diflucan)
Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal CYP-450 and sterol C-14 alpha-demethylation.
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Streptococcus pyogenes at 100X magnification.
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Rapid antigen detection test for group A beta-hemolytic streptococci.
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Posterior pharynx with petechiae and exudates in a 12-year-old girl. Both the rapid antigen detection test and throat culture were positive for group A beta-hemolytic streptococci.
