Medical Student Cheater: Bacterial Pharyngitis

Sunday, May 8, 2011

Bacterial Pharyngitis

Background

Pharyngitis, or sore throat, is often caused by infection. Common respiratory viruses account for the vast majority of cases, and these are usually self-limited. Bacteria are also important etiologic agents, and, when identified properly, may be treated with antibacterials, resulting in decreased local symptoms and prevention of serious sequelae.

The most common and important bacterial cause of pharyngitis is Streptococcus pyogenes. When suspected, bacterial pharyngitis can be confirmed with routine diagnostic tests and treated with various antibiotics. If left untreated, S pyogenes pharyngitis may lead to local and distant complications. To a lesser extent, bacteria other than S pyogenes are known to cause pharyngitis, and these are discussed in Causes.



Pathophysiology

Beta-hemolytic streptococci have the ability to cause large zones of hemolysis on blood agar, aiding in microbiological identification. Lancefield antigens, carbohydrates in the cell wall, provide further differentiation of streptococci. S pyogenes, which contains group A antigens and displays beta-hemolysis, is the most common species referred to as a group A beta-hemolytic streptococci (GABHS). Streptococcus dysgalactiae subspeciesequisimilis and some species from the Streptococcus anginosus group may share laboratory characteristics with S pyogenes but do not commonly cause human disease.Picture of Streptococcus pyogenes at 100 X magnification.

Perhaps the most important virulence factor of GABHS is the M protein. This protein, located peripherally on the cell wall, is required for invasive infection. T cells exposed to this M protein are postulated to cross-react with similar epitopes on human cardiac myosin and laminin, contributing to the pathogenesis of rheumatic heart disease. This protein provides a potential target for a GABHS vaccine, although successful widespread implementation of such a vaccine remains elusive. More than 100 M-protein serotypes have been described. Although individuals often develop lifelong immunity to one serotype, re-infection with a different serotype may cause disease.

GABHS contains a hyaluronic acid capsule, which also plays an important role in infection. Bacteria that produce large quantities of this capsule exhibit a characteristic mucoid appearance on blood agar and may be more virulent.

Certain GABHS exotoxins act as superantigens by up-regulating T cells. These superantigens can prompt a release of proinflammatory cytokines and may synergize with lipopolysaccharide. It has been speculated that these superantigens evade the pharyngeal immune response, resulting in proliferation of GABHS while permitting immune-mediated elimination of commensal organisms.

Adhesins enable GABHS attachment at sites such as the pharynx. This attachment allows for colonization and competition with normal host flora.

Some strains produce erythrogenic toxins, which cause the rash of scarlet fever in susceptible hosts.

GABHS is spread from person to person through large droplet nuclei. Consequently, close quarters (eg, barracks, daycares, dormitories) facilitate transmission. In temperate regions, the prevalence of GABHS infection increases in the colder months, presumably because of the tendency of people to congregate indoors. Spread within families is common. The risk of acquiring GABHS from an infected family member is 40%, and nearly one in four of infected individuals eventually exhibit symptoms. Twenty-four hours after appropriate antibiotics are initiated, the patient is no longer considered contagious.

Case reports and in vitro studies have speculated that toothbrushes, orthodontic appliances, and pets may carry and facilitate spread of GABHS, although these claims have not been validated by rigorous in vivo investigation.

GABHS is also a common cause of erysipelas, cellulitis, and necrotizing fasciitis and has been reported as a cause of pneumonia, toxic shock syndrome, and lymphangitis. The vast majority of these manifestations do not occur in the setting of pharyngitis.

Epidemiology:
Frequency

United States

Acute pharyngitis accounts for approximately 12 million annual ambulatory care visits in the United States. It ranks within the top 20 most-common primary diagnosis groups.

International

An estimated 616 million cases of GABHS pharyngitis occur annually worldwide. Rheumatic heart disease, which may be a consequence of GABHS pharyngitis, is estimated to cause about 6 million years of life lost annually. The burden of rheumatic heart disease disproportionately affects populations from developing countries. In terms of estimated global mortality, GABHS is one of the top 10 pathogens, behind HIV infection and malaria and ahead of tetanus and pertussis.
Mortality/Morbidity

Although GABHS pharyngitis is usually a self-limited entity, on average, a single episode in a child results in 1.9 days absence from school and a parent missing 1.8 days from work to care for the child. Children with GABHS pharyngitis experience symptoms for an average of 4.5 days.

In addition to symptoms localized to the oropharynx, GABHS pharyngitis may also cause the following suppurative and nonsuppurative complications:

  • Invasion of nearby structures may cause suppurative complications such as otitis media, sinusitis, peritonsillar abscess, retropharyngeal abscess, and cervical adenitis.
  • Nonsuppurative complications of bacterial pharyngitis include rheumatic heart disease and poststreptococcal glomerulonephritis. These entities are discussed in Complications.
Race

GABHS pharyngitis affects all races.
Sex

GABHS pharyngitis has no sexual predilection.
Age

GABHS pharyngitis is most common in individuals aged 5-15 years, although both infants and adults may also acquire the disease.

Clinical Manifestations:
History

The signs and symptoms listed below may be seen with many non-GABHS etiologies. Furthermore, individuals with GABHS pharyngitis may have only a few or mild features listed. Conjunctivitis, cough, hoarseness, coryza, diarrhea, anterior stomatitis, discrete ulcerative lesions, and a viral exanthem are all more consistent with an etiology other than GABHS.

  • Sore throat, usually with sudden onset
  • Odynophagia
  • Headache
  • Nausea, vomiting, and abdominal pain
Physical

  • Fever
  • Tonsillopharyngeal erythema
  • Exudates (patchy and discrete)
  • Beefy red swollen uvula
  • Lymphadenopathy (tender anterior cervical nodes)
  • Petechiae on the palate
  • Scarlatiniform rash (In susceptible hosts, this usually manifests within the first two days of symptoms and causes a finely papular, blanching, and erythematous rash. The neck is often first affected and then spreads along the trunk and limbs. Resolution, often at 3-4 days, occurs in roughly the same order of appearance and often results in desquamation of the involved areas.)
Predictive models can help determine the likelihood of GABHS pharyngitis based on the presence of fever, swollen tender anterior cervical lymph nodes, and tonsillar exudates and the absence of cough. Scores have been used to distinguish which patients merit further laboratory evaluation or treatment. The use of such clinical algorithms has been the source of much debate.

Causes

Viruses cause the vast majority of pharyngitis cases. Common agents include coronavirus, rhinovirus, adenovirus, parainfluenza, influenza, Epstein-Barr virus, cytomegalovirus, and HIV.
GABHS accounts for 15%-30% of pharyngitis cases in children and 5%-10% of cases in adults.
The following are bacteria other than GABHS that may cause pharyngitis:
Group C and G streptococci: Like GABHS, these pathogenic bacteria cause beta-hemolysis, form large colonies, and produce an M protein, yet neither are detected with rapid antigen detection tests (RADTs). Pharyngitis caused by either of these non-GABHS streptococci have a clinical presentation similar to that of GABHS pharyngitis and should be considered in patients with worsening symptoms and an initial negative RADT result. Diagnosis can be achieved with a normal bacterial throat culture and identification based on Lancefield antigens. These bacteria are an uncommon cause of acute pharyngitis in pediatric patients. 
  • Arcanobacterium haemolyticum: This gram-positive rod accounts for between 0.5% and 3% of pharyngitis cases. Clinical manifestations are similar to those of GABHS pharyngitis, although about half of patients with A haemolyticum pharyngitis develop a rash, which typically starts on the extensor surfaces; spares the palms, soles, and head; and moves centrally to involve the trunk with a maculopapular or scarlatiniform appearance. A haemolyticum exhibits variable susceptibility to penicillin and is identified more easily on human or rabbit blood agar than on sheep agar, the media traditionally used to identify GABHS.
  • Neisseria gonorrhoeae: Infection with this pathogen is associated with oral-genital contact and is often asymptomatic. N gonorrhoeae may be identified using chocolate or Thayer-Martin agar. Nucleic acid amplification tests from throat rinses appear to be a promising alternative. Because of increasing rates of fluoroquinolone resistance, ceftriaxone is now the only recommended option for treatment of pharyngeal gonorrhea. Treatment aimed at Chlamydia trachomatis is also recommended, since co-infection is common.
  • Mycoplasma pneumoniae: This atypical bacterium is increasingly being identified as an etiologic agent of pharyngitis. M pneumoniae pharyngitis may be associated with pulmonary findings.
  • Yersinia species: Both Yersinia enterocolitica and Yersinia pestismay cause disease. Pharyngeal plague has been linked to the consumption of camel meat.
  • Chlamydia trachomatis and Chlamydophila pneumoniae: Both of these organisms are rare causes of pharyngitis.
  • Corynebacterium diphtheriae: Toxigenic strains of this gram-positive bacillus are common causes of croup. Young patients with C diphtheriae pharyngitis often exhibit inspiratory stridor, sternal retraction, and a barking cough. In severe cases, a membrane formation may impair breathing. The incidence of C diphtheriae pharyngitis in developed countries is low because of high immunization rates.
Differentials

  • Acute retroviral syndrome
  • Infectious Mononucleosis
  • Peritonsillar Abscess
  • Pharyngitis, Viral
Laboratory Studies

The clinical features of GABHS pharyngitis overlap significantly with that caused by non-GABHS. Microbiological testing provides data to help determine who may benefit from GABHS-directed therapy. Laboratory evaluation of pharyngitis falls into two broad categories: rapid antigen detection tests (RADT) and throat culture.

RADTs offer the advantage of a speedy diagnosis, allowing for the proper administration, as well as proper withholding, of antibiotics. Drawbacks of RADTs include a higher cost and lower sensitivity compared with culture. While throat culture remains the criterion standard for diagnosis of GABHS pharyngitis, it has a 24-48 hour turnaround time and entails more technical involvement. Both RADTs and throat culture cannot be used to differentiate between infection and colonization and, in some cases, may influence a physician to overuse antibiotics. For example, a child with coronavirus pharyngitis and GABHS colonization may be prescribed antibiotics based on a false–positive RADT result. No matter what type of test is used in the outpatient setting, judicious selection of patients to be screened is imperative in order to avoid a large number of false-positive results.

Samples for RADT or throat culture should be obtained from the posterior pharynx or tonsils. Samples from the oral cavity result in a greatly reduced sensitivity.

Test of cure is not usually indicated except in special situations, including in patients with a history of rheumatic fever, in those who live in a community with an increased incidence of rheumatic fever or poststreptococcal glomerulonephritis, and in patients involved in outbreaks of GABHS pharyngitis in closed or semiclosed communities. Consideration should also be given to members of a family in whom "ping-pong" spread is presumed.

Antistreptococcal antibody tests have no role in the diagnosis of acute bacterial pharyngitis. However, they may be used to confirm a history of exposure to GABHS in patients with suspected poststreptococcal glomerulonephritis or acute rheumatic fever.

Rapid antigen detection tests
  • All RADTs yield high specificity, allowing for prompt treatment of GABHS pharyngitis without the concern of false-positive results.
  • Initial RADTs relied on latex agglutination to identify cell wall carbohydrates obtained after acid extraction, a method associated with low sensitivity.
  • Newer RADTs use optical immunoassay (OIA) technology to identify cell wall carbohydrates. These yield a sensitivity that may be similar to that of throat culture. Nevertheless, before removing confirmatory throat cultures from any given clinical practice, verification of increased sensitivity is recommended.
  • A newer generation of rapid tests uses nucleic acid identification to identify GABHS-specific sequences. Such assays yield a specificity of 95%-100% and sensitivity in the range of 86%-95%. Although these tests provide an answer in hours, they rely on equipment not available in most outpatient settings and often need to be performed at a location other than the office.
Throat culture

  • Considered the criterion standard of GABHS pharyngitis diagnosis, throat culture involves obtaining a sample from the posterior pharynx and tonsils and plating on sheep blood agar.
  • Bacitracin disks aid in differentiation of GABHS from other beta-hemolytic streptococci. A large zone of inhibition is found around GABHS but not around non–beta-hemolytic streptococci.
  • Cell wall carbohydrate detection assays, applied directly to the cultured bacteria, may also differentiate GABHS from other streptococci.
Imaging Studies

Imaging studies have no role in the diagnosis of bacterial pharyngitis. Lateral neck films may help to confirm the diagnosis of acute epiglottitis. CT scanning may aid in the diagnosis of some of the suppurative complications of pharyngitis, including abscesses and sinusitis.

Medical Care

Overzealous prescription of antibiotics for pharyngitis has been estimated to cost health payers $1.2 billion annually. Therefore, treatment of GABHS pharyngitis should be initiated only after confirmation with a RADT or throat culture. Alternatively, treatment in high-risk patients may be started before throat culture results are available, but antibiotics should be stopped if the culture returns negative results. Even though most cases of GABHS pharyngitis resolve after 3-4 days without treatment, antibiotics decrease the likelihood of local suppurative complications and acute rheumatic fever. Oral antibiotics should be administered for 10 days, although many recent studies show similar efficacy with shorter courses. Antibiotic therapy does not decrease the likelihood of poststreptococcal glomerulonephritis.

Oral penicillin V remains the preferred antibiotic to treat GABHS pharyngitis. In vitro, no isolate of GABHS has ever been resistant to penicillin. Other reasons favoring oral penicillin include its narrow spectrum, low cost, infrequent adverse effects, and proven track record. Nevertheless, GABHS is sensitive to many other antibiotics, thereby allowing flexibility based on numerous factors.

The following circumstances dictate that a choice other than penicillin V should be used:

  • Compliance: Oral penicillin requires multiple daily doses and a 10-day course. In patients unlikely to adhere to this regimen, one dose of intramuscular benzathine penicillin provides a depot that releases medication over the course. Azithromycin, cefdinir, and cefpodoxime may all be given in 5-day courses, although none of these medications is yet considered a first-line agent. Recent reports have supported the use of once-daily amoxicillin and verified its noninferiority to twice-daily penicillin or twice-daily amoxicillin.
  • Palatability: Some young children find oral penicillin unpalatable. Taste tests and many doctors’ experiences have shown amoxicillin to be much better tolerated. Amoxicillin’s similar spectrum and low cost make it a reasonable substitute.
  • Allergy: In patients with an immunoglobulin E (IgE)–mediated penicillin allergy, antibiotics that contain a beta-lactam ring (cephalosporins, amoxicillin) should be used with extreme caution. Although cross-reactivity between penicillin and cephalosporins is probably less than 10%, the risk of anaphylaxis justifies the consideration of other viable agents. Macrolides such as azithromycin and erythromycin may be used, although resistance has been reported in the United States and internationally.
  • Recurrence: Test of cure is not indicated when pharyngitis symptoms have resolved following treatment. In patients with recurrent symptoms, retreatment with an initial first-line agent (oral penicillin, benzathine penicillin, erythromycin, or a first-generation cephalosporin) is reasonable. Worth noting is the difficulty in differentiating between viral pharyngitis with GABHS carriage and actual GABHS pharyngitis. This becomes even more of an issue in patients with multiple recurrences. Between 5% and 15% of children are asymptomatic carriers during seasons when GABHS pharyngitis is most prevalent. A positive test result during a time of wellness may indicate GABHS carriage. When multiple recurrences are believed to be due to GABHS infection, clindamycin or amoxicillin/clavulanic acid is indicated. Benzathine penicillin with or without rifampin may be given when noncompliance is suspected to have been responsible for previous failures.
Surgical Care

In rare cases, pharyngitis spreads to adjacent structures and forms abscesses. In these cases, a drainage procedure performed by an interventional radiologist or otolaryngologist should be considered.

Consultations

An otolaryngologist should be consulted for local suppurative complications such as peritonsillar abscess and mastoiditis. Tonsillectomy may be considered in recurrent GABHS infection.

An infectious diseases expert may be consulted for patients with immunocompromising conditions or when an agent other than GABHS (eg, HIV) is suspected or confirmed.

Diet

Allow a regular diet as tolerated in patients with bacterial pharyngitis. Warm liquids may provide symptomatic relief.

Activity

Encourage rest during the acute illness.

Medication Summary

The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications.

Antibiotics:
Class Summary

Oral penicillin is currently the drug of choice for GABHS pharyngitis. Amoxicillin remains a reliable alternative and offers advantages in terms of easier dosing and increased palatability.

Tetracyclines and trimethoprim/sulfamethoxazole should not be used to treat GABHS pharyngitis owing to higher rates of resistance.

Penicillin G benzathine (Bicillin L-A, Permapen)

Interferes with synthesis of cell wall by binding to penicillin-binding proteins. Penicillin is the drug of choice to treat GABHS pharyngitis, as recommended by expert committees of the American Heart Association, American Academy of Pediatrics, and the Infectious Disease Society of America, because of proven efficacy, safety, narrow spectrum, and low cost. Preferred for patients unlikely to complete a full 10-d PO course. S pyogenes remains universally sensitive to penicillin.

Penicillin VK (Beepen VK)

Treatment of choice for GAS pharyngitis, as recommended by expert committees of the American Heart Association, American Academy of Pediatrics, and the Infectious Disease Society of America, because of its proven efficacy, safety, narrow spectrum, and low cost. Inhibits biosynthesis of cell wall by binding to penicillin-binding proteins. Bactericidal against sensitive organisms when adequate concentrations are reached and most effective during stage of active multiplication. Inadequate concentrations may be ineffective. GABHS remains uniformly susceptible in vitro.

Amoxicillin (Amoxil, Biomox, Trimox)

Interferes with synthesis of cell wall mucopeptides by binding to penicillin-binding proteins. Often used in place of oral penicillin VK in young children. Efficacy equal to penicillin, and often chosen because of the unpalatability of the penicillin susp.

Azithromycin (Zithromax)

Inhibits RNA-dependent protein synthesis at the 50s ribosome. Can be given as a single daily dose, is better tolerated than erythromycin in patients who are allergic to penicillin, and is effective in a 5-d course. However, much more expensive and should be avoided as first-line therapy in patients with streptococcal pharyngitis. Sporadic resistance has been reported.

Erythromycin (E.E.S., E-Mycin, Ery-Tab, Erythrocin)

Inhibits RNA-dependent protein synthesis at the 50s ribosome. An option in those with severe allergic reactions to beta-lactam antibiotics. Sporadic resistance has been reported.

Clindamycin (Cleocin)

Belongs to the lincosamide class of antibiotics. Binds to the 50s ribosome and prevents bacterial protein synthesis. Is an option for symptomatic patients with multiple, recurrent episodes of pharyngitis proven by culture or rapid antigen testing.

Cephalexin (Keflex)

First-generation cephalosporin that arrests bacterial growth by inhibiting bacterial cell wall synthesis. Bactericidal activity against rapidly growing organisms. Oral cephalosporins are highly effective for streptococcal pharyngitis, and several studies have found them to have slightly higher eradication rates than those of penicillin. Second-line agents in the treatment of patients with GABHS pharyngitis.

Further Inpatient Care

Droplet precautions should be observed until 24 hours after the initiation of antibiotics.

Further Outpatient Care

Patients with bacterial pharyngitis should be kept out of daycare, school, or work until 24 hours after the initiation of antibiotics.

Complications
GABHS infection may result in suppurative or nonsuppurative complications.

  • Local complications: These result from untreated infection that spreads to adjacent sites. Some of the more common of these suppurative infections include retropharyngeal abscess, peritonsillar abscess, sinusitis, cervical lymphadenitis, otitis media, and mastoiditis.
  • Acute rheumatic fever: This disorder usually occurs 2-4 weeks after an episode of pharyngitis. Administration of proper antibiotics up to 9 days after the onset of pharyngeal symptoms has been shown to prevent this manifestation. Major manifestations of acute rheumatic fever include carditis, polyarthritis, chorea, erythema marginatum, and subcutaneous nodules. Minor criteria include fever, polyarthralgia, elevated leukocyte count, elevated erythrocyte sedimentation rate, and prolonged P-R interval.
  • Rheumatic heart disease: This is the chronic valvular manifestation of acute rheumatic fever. The mitral valve is the site most often affected, and either regurgitation or stenosis may result. In individuals with rheumatic heart disease, long-term secondary prophylaxis, often with benzathine penicillin, decreases the risk of subsequent episodes of acute rheumatic fever and further heart damage.
  • Poststreptococcal glomerulonephritis: This usually occurs 1-3 weeks following GABHS pharyngitis. Poststreptococcal glomerulonephritis, which may also follow a GABHS skin infection, has not been shown to be preventable with proper administration of antibiotics. Patients often present with hematuria, edema, and hypertension.
Prognosis

GABHS pharyngitis is usually a self-limited illness. Throat symptoms resolve within 3-4 days in untreated patients. Administration of penicillin shortly after disease onset may shorten symptoms by 1-2 days.

Patient Education

Symptomatic relief may be provided by warm saline gargles, throat lozenges, and ibuprofen.
Patients with bacterial pharyngitis should be instructed to complete a full course of antibiotics, even if symptoms resolve.

Copyright © 1994-2011 by MEDSCAPE WebMD LLC.

1 comment:

  1. Hi Friends,

    Pharyngitis is inflammation of the pharynx, which is in the back of the throat, between the tonsils and the voicebox. A person with bacterial pharyngitis has inflammation of the throat, due to a bacterial infection. It is very common, usually caused by the group A streptococcus bacteria. Thanks a lot!

    ReplyDelete

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