Bacterial Pharyngitis

Editorial comment: This is a paper submitted by the following medical students for the pharmacology minicourse. Richard P. Bobbin, PhD, Professor of Otolaryngology and Professor of Pharmacology

Louise-Ann Gombako
Melissa Wainwright

Pharyngitis is defined as an infection or irritation of the pharynx and tonsils. The peak incidence is seen in children between the ages of 4-7 but pharyngitis can be recurrent throughout life. The largest number of cases are seen during the winter [1]. There are many agents which cause pharyngitis. Viral infections account for approximately 70% of all pharyngitis [2], with bacteria causing 20 to 30% of pharyngitis. Viral pharyngitis is usually self-limited and is treated symptomatically. Bacterial pharyngitis, although it can be self-limiting also, has important suppurative and non-suppurative sequelae which can be avoided by the use of antibiotics. The most common agents involved in bacterial pharyngitis are Group A and Group C -Hemolytic Streptococcus. Other uncommon bacteria include Group G -Hemolytic Streptococcus, Anaerobes, Arcanobacterium haemolyticus, Chlamydia pneumoniae, Mycoplasma pneumoniae, Neisseria gonorrheae, and Corynebacterium diphtheriae [1]. In the following paragraphs, the bacteria which most commonly cause pharyngitis will be discussed along with their treatments.

Group A -Hemolytic Streptococcus is an extremely important bacteria not only because it is the most common bacteria to be cultured in pharyngitis but it also causes some of the most damaging complications. Group A Streptococcus is a Gram positive cocci which is adept at colonizing the skin and throat. It causes an age-related pharyngitis with 40% of school children who have pharyngitis having a Group A Streptococcus infection. The incidence drops to 10% in adults [2,3]. Most patients will present with a sudden onset of fever, chills, and pharyngitis. It is also associated with headaches, cervical lymphadenopathy, exudative tonsillitis, nausea, vomiting, and palatal petechiae [1,4]. There is usually no rhinorrhea or cough. The infection itself can be self-limiting or even asymptomatic. The problem lies in the many enzymes and toxins produced by this bacteria many of which participate in non-suppurative sequelae.

There are three types of sequelae to Group A Streptococcus pharyngitis: suppurative, toxin-mediated, and non-suppurative. The suppurative sequelae include more commonly peritonsillar abscesses and retropharyngeal abscesses and less commonly, sinusitis, mastoiditis, and otitis media [2]. The toxin-mediated sequelae include Scarlet Fever and Toxic Shock-like Syndrome. These are both caused by pyrogenic exotoxins produced by the Streptococcus. Scarlet Fever presents as a rash which begins on the trunk and moves outward. It is most apparent in the skin folds and desquamation may occur with recovery. A "strawberry tongue" may also be seen in which the papillae of the tongue become edematous and protrude upward making the tongue look like a strawberry [2]. The Toxic Shock-like Syndrome presents in a similar fashion as the Toxic Shock Syndrome of Staphylococcus Aureus.

The non-suppurative sequelae, or delayed antibody mediated diseases of Streptococcus are Acute Rheumatic Fever and Acute Glomerulonephritis [2]. Acute Rheumatic Fever (ARF) is thought to be a cross-reaction between the antibodies made to the M protein of Group A Streptococcus and cardiac myocytes. The M protein is a protein produced by the Streptococcus which inhibits phagocytosis. It also confers the serotype, of which there are over 80, to the Streptococcus [1,2]. ARF appears about 2-5 weeks after the pharyngitis and the Jones Criteria is used to diagnose it [1,2]. Acute Glomerulonephritis appears about 1 week after the Streptococcus pharyngitis and the patient presents with proteinuria, hematuria, and possibly hypertension. It usually has a good prognosis especially in the pediatric population [1].

Diagnosis is important because of treatment. Since resistance is becoming a problem in so many bacteria, it is important to diagnose the bacteria which are causing the problem and treat them accordingly [5]. The test used to diagnose Group A -Hemolytic Streptococcus is the Rapid Streptococcal Antigen Test. Results are obtained quickly but the test is more expensive than a culture (which still remains the gold standard for diagnosis) [1,5]. The Antigen Test is also very specific but not very sensitive, giving many false negatives [1,5]. Therefore, a negative on the Antigen Test requires a secondary culture.

Another common bacteria found in bacterial pharyngitis is the Group C -Hemolytic Streptococcus. Less commonly, Group G -Hemolytic Streptococcus will be found. Both produce symptoms similar to Group A -Hemolytic Streptococcus but neither are associated with the non-suppurative sequelae [2] nor generate a major antibody response [1].

Anaerobes are suspected when the pharyngitis is associated with a foul breath odor. Predisposing factors for an anaerobic pharyngitis are malnutrition, leukopenia, immunodeficiency, and therapeutic neck irradiation [1,2]. Complications with an anaerobic infection include peritonsillar abscesses or postanginal septicemia (Lemierre's Disease) with jugular vein thrombophlebitis [1].

Arcanobacterium haemolyticus is a gram positive to gram variable rod and presents with symptoms similar to Group A -Hemolytic Streptococcus. It can even have a scarlatiniform rash which begins on the extensors and moves inward. Many patients will also have a cough associated with the infection, which is unlike infections caused by Group A Streptococcus. Chlamydia pneumoniae and Mycoplasma pneumoniae will also present with a cough. Mycoplasma may also present with rhinorrhea [1].

Neisseria gonorrhoeae are asymptomatic but present with multiple findings on physical exam. This bacteria should be considered when negative blood cultures are returned on sexually active adolescents and adults, especially if ragged bordered oropharyngeal ulcers are found [1,2].

Corynebacterium diphtheriae is rarely found today in the United States because of immunizations, however each year a few cases are still seen. Although this infection begins with just a mild sore throat and low-grade fever, a pseudomembrane begins to develop on the tonsils and pharynx and the bacteria begin to secrete their toxin. This product has cardiac and neurologic toxicity and eventually the patient will develop respiratory exhaustion and death [1,2].

Treatments of Bacterial Pharyngitis

Non-Pharmacological, Non-Surgical Interventions

• Gargling warm salt water
• Drink warm liquids
• Rest

Pharmacological Interventions

Listed below are drugs that are usually effective for the treatment of bacterial pharyngitis.

Side Note: Group A streptococcus is usually sensitive to penicillin. However, some GABHS have developed tolerance to the drug through a microbial shift toward the selection of beta-lactamase producing organisms. Organisms such as, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, and a variety of anaerobes [3]. Co-colonization of these beta-lactamase producing organisms with Group A beta-hemolytic strep cause the GABHS to become tolerant to Penicillin. Penicillin is also known to eradicate alpha hemolytic strep (non-pathogenic) strains that produce natural antibiotic substances and cause the more pathogenic strains to flourish.

The problem caused by the use of Penicillins has resulted in Cephalosporins becoming the drug of choice in the treatment of bacterial pharyngitis. Cephalosporins are less harsh on the non-pathogenic alpha hemolytic strains. In comparison with Penicillin, Cephalosporins have a much higher bacteriologic and clinical cure rate and a lower failure rate. Cephalosporins can be given once or twice a day with food, and several have demonstrated efficacy with treatment duration of just five days in comparison to penicillin's ten days regimen.

Penicillin

Use: Respiratory infections, scarlet fever, erysipelas, OM, pneumonia, skin and soft tissue infections, gonorrhea; effective for G+ cocci esp. S. pyogenes.

Suggested Drugs: Penicillin G benzathine (IV/IM), Penicillin V potassium (Oral).

MOA: interferes with cell wall replication of susceptible organisms; osmotically unstable cell wall swells, bursts from osmotic pressure, which results in cell death.

Pharmacokinetics: IM- very slow absorption, half-life 30-60min; excreted in urine, feces, breast milk; crosses placenta.

Adverse effects: Anemia, increased bleeding time, bone marrow suppression, granulocytopenia, nausea, vomiting, diarrhea, oliguria, proteinuria, hematuria, lethargy, coma and convulsions.

Interactions: Decreased anti microbial effects with tetracycline and erythromycin

Contraindications: Hypersensitivity to penicillins and cephalosporins; neonates, pregnancy lactation, and severe renal disease.

Cephalosporins

Use: Its coverage for G+ and G- organisms depends on the generation of the drug. Used for upper and lower respiratory infections, OM, UTI, skin bone and joint infections.

Suggested Drugs: 1st or 2nd generation cephalosporin: cefuroxime (2nd), cefpoxdoxime (2nd), cefaclor (2nd), cefadroxil (1st), ceftriaxone (3rd-used mostly for G- esp. gonococcal). These drugs eliminate GABHS from throat in 97% of cases.

MOA: Inhibits cell wall synthesis, which renders cell wall osmotically unstable, leading to cell death by binding to cell wall membrane.

Pharmacokinetics: This varies depending on the drug used. Most are excreted unchanged in the urine.

Adverse effects: Headache, dizziness, weakness, nausea, vomiting, proteinuria, nephrotoxicity, renal failure, leukopenia, anemia, rash

Contraindications: Hypersensitive to penicillin, cephalosporin, infants<1month.

Macrolide Antibiotics

Use: infx caused by N. gonorrhae, mild to mod resp. tract infx. caused by S. pneumoniae, M.pneumoniae, C. diphtheria, S. pyogenes, Chlamydia pneumoniae.

Suggested Drugs: Erythromycin, Azithromycin, Clarithromycin

MOA: Binds to 50S ribosomal subunit of susceptible bacteria and suppress protein synthesis.

Pharmacokinetics: azithromycin has a half-life of 11-57hrs, excreted in bile feces and unchanged in urine. Erythromycin has a half-life of 1-2hrs; The drug is metabolized by liver and excreted in bile and feces. Clarithromycin has a half-life of 4-6hrs; metabolized by liver and excreted in bile and feces.

Adverse effects: Hepatotoxicity, rash, palpitations, nausea, vomiting, diarrhea, vaginitis, hearing loss with erythromycin and cholestatic jaundice with azithromycin.

Contraindications: Hypersensitivity to azithromycin or erythromycin or preexisting liver or cardiac disease.

Tetracycline

Use: Chlamydia trachomatis, gonorrhea, uncommon G+, G- organisms, syphilis, rickettsial infx.

MOA: Inhibit protein synthesis and phosphorylation in microorganisms; bacteriostatic.

Pharmacokinetics: Half-life 6-10 hrs. Excreted in urine, breast milk, crosses placenta; 20-60% is protein bound.

Adverse effects: Fever, headaches, eosinophilia, neutropenia, hemolytic anemia, dysphagia, discoloration of deciduous teeth, oral candidiasis and oral ulcers, nausea abdominal pain enterocolitis, hepatotoxicity, foliative dermatitis, and angioedema.

Contraindications: Hypersensitivity to tetracyclines, children <8yrs, pregancy, lactation, renal and hepatic disease.

Amoxicillin Calvulanate potassium (Augmentin, Calvulin)

Use: G+ cocci (S. aures, S. pyogenes, S. pneumoniae); G- cocci (N. gonorrhoeae, meningititis); G+ bacilli (C. diphtheriae, L.monocytogenes).

It is used to treat sinus infections, pneumonia, OM, skin, UTI and some beta-lactamase producing organisms.

MOA: Interferes with cell wall replication of susceptible organisms; the cell wall rendered osmotically unstable, swells and burst from osmotic pressure; Combination increase spectrum of activity against Beta-lactamase resistant organisms.

Pharmacokinetics: Peak at 2hrs. Half-life is 1 - 1 1/3 hr. Metabolized in liver, excreted in urine, crosses placenta and enters breast milk.

Adverse effects: Anemia, bone marrow depression, granulocytopenia, leukopenia, thrombocytopenic purpura, and glomerulonephritis.

Contraindications: Hypersensitivity to penicillins, and cephalosporins; neonates, pregnancy.

Surgical Interventions

Tonsillectomy--If patient has six or seven documented episodes of GABHS tonsillopharyngitis over one or two years despite antibiotic tx., a tonsillectomy should be considered. The procedure reduces the frequency of sore throats and speciffically, of GABHS tonsillopharyngitis for two-three years after surgery. Consideration of non-group A streptococcal exudative pharyngitis episodes as a reason for surgery remains controversial.

References:

1. Middleton, Donald B.: Pharyngitis. Primary Care; Clinics in Office Practice, Vol 23, Num 4, Dec 1996, pp 719-738.
2. Hunsaker, Darrell H. and Boone, John L. Etiology of Infectious Diseases of the Upper Respiratory Tract. In: Ballenger, John Jacob and Snow, Jr., James B. eds., Otorhinolaryngology: Head and Neck Surgery. Williams and Wilkins, 1996, pp 69-79.
3. Pichichero, Michael E.; Sore Throat After Sore Throat After Sore Throat; Postgraduate Medicine, Vol 101, Num 1, Jan 1997, pp205-225.
4. Perkins, Allen; An Approach to Diagnosing the Acute Sore Throat; American Family Physician, Jan 1997, pp131-138.
5. Garcia-de-Lomas, Juan and Navarro, David; New Directions in Diagnostics; Pediatric Infectious Disease Journal, Vol 16, Num 3, Mar 1997, ppS43-S48.
6. Skidmore-Roth, Linda; Mosby's 1998 Nursing Drug Reference; Mosby Publishing, St. Louis 1998.