Pediatric Pharyngitis

Background

Pharyngitis is a leading cause of pediatric ambulatory care visits. Examination of patients who present with sore throat may reveal tonsillitis, tonsillopharyngitis, or nasopharyngitis.^[1] The absence of pharyngeal inflammation or the presence of rhinorrhea is much more likely to be associated with viral infection. However, no physical findings clearly separate group A beta-hemolytic streptococci (GABHS) from viral, other bacterial, or noninfectious causes.

The primary concern for pharyngitis in children aged 2 years or older is that untreated GABHS pharyngitis may subsequently cause rheumatic fever. To prevent this sequela, institute adequate antimicrobial therapy within 9 days of infection. Rapid antigen detection assays for GABHS are diagnostic if positive because the specificity of such tests is 98-99% (ie, 1-2% false-positive results); however, their sensitivity is only 70% (ie, 30% false-negative results), necessitating follow-up cultures for negative results.

The drug of choice for treatment of GABHS pharyngitis remains penicillin V, although many experts recommend a higher dosage than was used in the past. Other bacteria that occasionally cause pharyngitis and require antimicrobial therapy include gonococcus; Francisella tularensis; groups B, C,^[2] and G streptococci; Arcanobacterium hemolyticum; and Treponema pallidum. No treatment is of any benefit for the usual viral causes of pharyngitis.

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Pathophysiology and Etiology

Multiple entities can cause irritation and inflammation of the pharynx. In children, such causes range from viruses (eg, adenoviruses, enteroviruses, and Epstein-Barr virus [EBV]), which often require only supportive therapy, to bacterial pathogens (eg, GABHS), which require antibiotic therapy. For all cases of pediatric pharyngitis, whether of bacterial or viral origin, supportive care is necessary to prevent associated symptoms such as dehydration.

Primary bacterial pathogens account for approximately 30% of cases of pharyngitis in children. These include the following:

• GABHS (common)
• Arcanobacterium hemolyticum (7% of adolescents and adults with pharyngitis)
• Group C streptococci (uncommon)
• Group G streptococci (uncommon)
• Neisseria gonorrhoeae (uncommon)
• Corynebacterium diphtheriae (rare)

No pathogen is isolated in nearly 30% of cases, and viruses are isolated in approximately 40% of cases. Other probable copathogens in children include the following:

• Staphylococcus aureus
• Haemophilus influenzae
• Moraxella (Branhamella) catarrhalis
• Bacteroides fragilis
• Bacteroides oralis
• Bacteroides melaninogenicus
• Fusobacterium species
• Peptostreptococcus species
• Chlamydia trachomatis (less common)
• Mycoplasma pneumoniae (less common)

GABHS is the primary organism of concern in most pediatric cases of pharyngitis because appropriate antibiotic therapy is effective and can eliminate the cardiac complications of rheumatic fever. More than 80 M-protein types of GABHS have been isolated. Serotypes 1, 3, 5, 6, 18, 19, and 24 are associated with rheumatic fever (and thus are referred to as rheumatogenic forms), whereas others, such as serotypes 49, 55, and 57, are associated with pyoderma and acute poststreptococcal glomerulonephritis.

GABHS pharyngitis is spread via respiratory droplets through close contact. It has an incubation period of 2-5 days.

A study found that in adolescents and young adults, Fusobacterium necrophorum pharyngitis was more common than group A beta-hemolytic streptococcal (GAS) pharyngitis. European data suggest that in patients aged 15 to 30 years, Fusobacterium necrophorum causes at least 10% of cases of pharyngitis. The study also observed that F. necrophorum was the primary cause of Lemierre syndrome in this age group.^{[3, 4]}

Viruses that may cause acute viral pharyngitis include the following:

• EBV (mononucleosis) - Produces a shaggy white membrane
• Rhinovirus
• Adenovirus
• Parainfluenza virus
• Coxsackievirus
• Coronavirus
• Echovirus
• Cytomegalovirus (CMV)

Causes of chronic pharyngitis (usually noninfectious) include the following:

• Irritation from postnasal discharge of chronic allergic rhinitis
• Chemical irritation
• Neoplasms and vasculitides

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Epidemiology

United States statistics

Approximately 10% of children seen by medical care providers each year have pharyngitis, and 25-50% of these children have GABHS pharyngitis. Approximately 20% of asymptomatic children are chronic carriers of GABHS.

International statistics

The entire range of pharyngitis-causing pathogens is observed throughout the world. Certain pathogens that are virtually nonexistent in the United States cause pharyngitis in other areas. A good example is diphtheria, which has been nearly eradicated in the United States through immunizations. According to the Red Book, from 1990-1995, approximately 48,000 cases of epidemic diphtheria were reported in the former Soviet Union and central Asia.^[5]

Given the high case-fatality rate of 3-23% and the increased geographic mobility of people, the potential for worldwide spread of diphtheria is a cause for concern. Consider rare or unsuspected causative agents in afflicted individuals who have traveled to high-risk areas or in individuals who have emigrated from these regions, especially if they have not been immunized.

Age-, sex, and race-related demographics

Pharyngitis occurs in all age groups. The peak prevalence of GABHS pharyngitis is in children aged 5-10 years. In children younger than 2 years, most pharyngitis is of viral origin, although GABHS is responsible in rare instances. Viral pharyngitis occurs in persons of all ages. No sex predilection exists. Prevalence is equal among all races.

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Prognosis

For all types of pharyngitis, the prognosis is excellent. Streptococcal pharyngitis has a 5- to 7-day course, and symptoms usually resolve spontaneously, without treatment—though in rare cases, rheumatic fever can develop if GABHS is left untreated. Rarely, peritonsillar abscesses or other local complications develop; these may call for surgical intervention. With supportive care to prevent dehydration and pain, pharyngitis, for the most part, is a self-limiting disease.

Although the prevention of rheumatic fever is the primary reason for treating GABHS, the following interesting observations were made during outbreaks of rheumatic fever in 1985 and 1990:

• No previous significant increases in GABHS were noted in the communities before the outbreaks; the outbreaks were observed in middle-class areas, where compliance rates with medical therapy are relatively high
• In these outbreaks, unlike most previous outbreaks, severe pharyngitis was rarely noted; only 46% of patients reported even having a recent sore throat, and only 24% had sore throats serious enough to cause them to seek medical care; in addition, almost 20% of cases were in children who received antibiotics for pharyngitis (antibiotic type, length of therapy, and compliance issues were not recorded)

Therefore, outbreaks may, in fact, be most related to the “rheumatogenicity” of the GABHS.

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Patient Education

Emphasize the importance of the patient’s completing a full course of antibiotics, regardless of symptom response. Instruct families to encourage adequate hydration and to use antipyretics for pain and fever. In addition, instruct parents to seek immediate medical care or consult their primary medical provider if signs of dehydration occur or symptoms worsen.

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History

Clinical differentiation of the various pathogens of pharyngitis on the basis of history or physical examination is difficult. As Feinstein et al noted in 1962, “[t]he only typical feature of streptococcal infections is the failure to show a single, consistent, typical feature.”

A history of exposure to known carriers, fever, headache, and abdominal pain in conjunction with sore throat suggests group A beta-hemolytic streptococcal (GABHS) pharyngitis. Involvement of other mucous membranes (eg, conjunctivitis, coryza) suggests a viral etiology. Age may also dictate the level of concern because GABHS is rarely a true rheumatogenic pathogen in children younger than 2 years.

Because supportive care is a primary goal in all cases, historical information regarding oral intake and hydration status is important. Obtain information about previous treatments, treatment failures, and medication allergies.

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Physical Examination

Although no single finding or combination of physical findings distinguishes GABHS from a viral etiology, several findings are suggestive, including the following:

• Enlarged tonsils
• Pharyngeal erythema
• Tonsillar exudates with necrotic crypts
• Soft-palate petechiae
• Tender cervical adenopathy
• Scarlet fever rash (punctate erythematous macules and fine papules with reddened flexor creases and circumoral pallor), the so-called sandpaper rash
• Conjunctivitis (more common with adenovirus infections)

GABHS pharyngitis is often associated with headache, pharyngeal exudate (see the image below), painful cervical adenopathy, gastrointestinal (GI) symptoms, chills, and high fever.

View Image

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 ....

Viral pharyngitis is usually associated with sneezing, rhinorrhea, and cough. For example, H1N1 influenza can present with sore throat but may also have other associated symptoms (eg, rhinorrhea and cough). Mononucleosis is typically exudative with extensive false membranes. Herpangina (usually coxsackievirus A) is associated with papulovesicular lesions of the skin (ie, hand-foot-and-mouth disease). Diphtheria (rare in developed countries) is associated with a thick gray membrane that is difficult to remove, is highly friable, and bleeds if manipulated.

It is important to look for tonsillar asymmetry, which may be a sign of peritonsillar abscesses. This condition can occur in conjunction with soft palate bulging and deviation of the uvula. Pay particular attention to signs of dehydration because supportive care is a primary concern and essential regardless of the etiologic agent.

Although no single or combination of physical findings is specific for distinguishing GABHS from viral etiologies, the Infectious Diseases Society of America (IDSA) has attempted to categorize some of the clinical differentiators. This clinical decision tool was tested in an emerging health care system and was found to be somewhat helpful in reducing unnecessary antibiotic use in resource-limited settings. Rates of disease outbreaks and availability of laboratory and clinical screening tools can help guide management. The IDSA categorization is as follows:

• Category 1 (probable viral pharyngitis) - Conjunctivitis, coryza, cough, diarrhea, viral-like exanthems
• Category 2 (suggestive of possible bacterial pharyngitis) - Fever of more than 38.5°C, tender cervical nodes, headache, petechia of the palate, abdominal pains, or sudden onset (< 12 h).

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Complications

Complications of pharyngitis may include the following:

• Rheumatic fever and subsequent rheumatic heart disease
• Poststreptococcal glomerulonephritis
• Peritonsillar abscess
• Systemic infection
• Otitis media
• Mastoiditis
• Septicemia or toxic shock syndrome
• Rhinitis
• Sinusitis
• Pneumonia

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Approach Considerations

Rapid testing and throat culture

A throat culture remains the standard for diagnosis, though results can take as long as 48 hours. Throat culture results are highly sensitive and specific for group A beta-hemolytic streptococci (GABHS), but results can vary according to technique, sampling, and culture media.

Most institutions and clinics have rapid testing, which is useful when immediate therapy is desired. Rapid testing can be highly reliable when used in conjunction with throat cultures. Several rapid diagnostic tests are available. Compared with throat culture, such tests are 70-90% sensitive and 95-100% specific.

Rapid screening followed by culture has become the standard in most institutions, especially in developed countries. In repeated investigations, rapid screening with throat culture backup for rapid screen–negative cases has continued to be the most proven strategy. This approach potentially minimizes unnecessary antibiotic administration by helping limit antibiotic use to cases with positive rapid screen findings or those with subsequent positive culture findings.^[6]

This approach arises out of the somewhat low sensitivity and specificity of clinical screening. Although the categorization of clinical differentiators developed by the Infectious Diseases Society of America (IDSA) can assist in clinical management (see Presentation), rapid screening followed by culture remains the best combination when resources are available.

The IDSA added that testing for Group A Streptococcus usually is not recommended for the following: patients with sore throat and accompanying symptoms (e.g., cough, rhinorrhea) that strongly suggest a viral etiology; children aged < 3 years, because acute rheumatic fever is extremely rare in this age group; and asymptomatic household contacts of patients with Group A Streptococcus pharyngitis.^{[7, 8]}

Testing for viral causes

If Epstein-Barr virus (EBV) is considered, obtain a complete blood count (CBC) to detect atypical cells in the white blood cell (WBC) differential, along with a Monospot test (or another rapid heterophile antibody test). EBV can also produce a subclinical hepatitis with a slightly elevation in aminotransferases.

Monospot findings are often negative in children younger than 6 years with EBV infections and in the first week of symptoms. In adolescents, Monospot testing detects approximately 90% of positive cases ultimately diagnosed with EBV-specific serologies.

Other viral pathogens usually do not call for further diagnostic testing, but viral cultures can be obtained. Viruses can be cultured in special media.

During viral outbreaks (eg, H1N1 influenza), if associated symptoms of the outbreak virus may initially include sore throat, one may opt to screen for streptococcal infection immediately or may elect to screen later, if symptoms persist, in order to rule out Streptococcus as the primary cause of the fever and sore throat.

Radiography

Imaging studies are usually not necessary unless a retropharyngeal, parapharyngeal, or peritonsillar abscess is suspected. In such cases, a plain lateral neck film can be used as an initial screening tool.

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Approach Considerations

For patients with signs of dehydration, administer adequate oral or intravenous (IV) fluids. Remember that pain may limit oral intake, complicating hydration maintenance in the patient. Rarely, small children with pharyngitis who have signs and symptoms of dehydration after refusing to drink may require hospitalization for IV hydration. Usually, even patients who require IV hydration in the emergency department (ED) consume enough oral fluids after their IV fluid bolus to allow home management with close and adequate follow-up care and good instructions for returning if the condition worsens or oral intake is poor.

For patients with group A beta-hemolytic streptococcal (GABHS) pharyngitis, the antibiotic treatment of choice is penicillin. Provided that rapid testing is available, physicians can decide, on the basis of the clinical severity of the pharyngitis, whether to initiate therapy immediately if a rapid test is positive for GABHS or to delay therapy until culture results are obtained. The issue of early versus delayed therapy has several considerations.^[9]

Benefits of early treatment include the following:

• Therapy within 48 hours of symptom appearance appears to shorten the duration of symptoms
• Early therapy limits spread to other children
• Early therapy allows the patient and family to return to their usual routine sooner; because more than 80% of patients have culture-negative results after 24 hours of therapy, the child should remain out of school or daycare for 24 hours after starting therapy; they must also be fever free before returning
• Early therapy limits losses to follow-up

Disadvantages of early treatment include the following:

• Early therapy may lead to a higher failure rate secondary to an inability to create an immune response to the infection
• Rheumatic fever may still be prevented if antibiotic therapy is initiated within 9 days of symptom onset^[10]
• Possible drug reactions and expenses may be avoided by refraining from immediately treating cases caused by pathogens other than GABHS (viruses in particular)

Make decisions on an individual basis, taking into account available testing, the severity of symptoms, the feasibility of arranging follow-up care, and the need for patients and their families to quickly return to their regular routine.

For patients with viral pharyngitis, care should be supportive, with antipyretics for pain and fever.

Some have also suggested that steroid use, dexamethasone in particular, may reduce pain and decrease symptom duration for both viral pharyngitis and streptococcal pharyngitis. This has been primarily shown in the adult population. In children, the length of symptoms has been shown to be minimally improved with adjunct steroid use; however, steroids might be considered in children with significant symptoms or discomfort.^[11]

Refer to the primary care physician for follow-up care. For most patients, no specific diet is needed, but adequate fluid intake and hydration are of vital importance. Monitor the patient to prevent secondary dehydration. To limit the spread to other individuals who have not been exposed, the patient should avoid school and new contacts during the initial 24 hours after beginning antibiotic therapy for GABHS and until free of fever.

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Pharmacologic Therapy

Penicillin is the typical therapy for GABHS pharyngitis, in conjunction with prevention of dehydration and supportive care for pain. Improved compliance with regimens has been noted when penicillin treatment is administered 2-3 times daily, as compared with traditional regimens comprising 4 daily doses. Treatment regimens with as few as 2 doses per day have been proved to be effective.^[12] Administer a minimum of 20 mg/kg/day; larger children generally should receive 500 mg divided into 2 daily doses for 10 days.

Initial studies using a 5- to 7-day course of penicillin showed a decline in the number of GABHS positive follow-up throat cultures, from 53% to 18%. Subsequent 10-day courses of penicillin proved to be the most beneficial in eradicating GABHS from the pharynx. Therefore, the diagnosis and proper treatment of GABHS are of vital importance.

However, a Cochrane review of 20 studies (including 13,102 acute GABHS pharyngitis cases) that compared short duration of antibiotic therapy with standard duration of therapy for treating acute streptococcal pharyngitis in children determined that short-duration treatment resulted in shorter periods of fever and sore throat, less risk of early clinical treatment failure, and comparable rates of early bacteriologic treatment failure (or late clinical recurrence).^[13]

The authors concluded that a 3- to 6-day regimen of oral antibiotics had an efficacy comparable with that of a standard-duration 10-day oral penicillin regimen in treating children with acute GABHS pharyngitis.^[13] Shorter courses of antibiotics could limit antibiotic use, reduce cost, and potentially minimize antibiotic resistance; however, the long-term impact on the prevention of rheumatic heart disease is not known and requires further study.

Several other medications, including some that are more palatable and meet with better compliance, have been approved to treat GABHS pharyngitis. For example, amoxicillin has often been used in place of penicillin; however, neither has been determined to possess a significant microbiologic advantage over penicillin. One preliminary report has shown amoxicillin taken once daily to be effective.

Cephalosporins also have been used, but it is questionable whether failure rates are any better than those achieved with penicillin. Cephalosporins resist degradation by beta-lactamases and are very effective against copathogens. First- or second-generation cephalosporins are preferred. Cephalosporins use to treat pediatric pharyngitis include cephalexin, cefadroxil, cefuroxime, cefixime, cefdinir, and cefpodoxime. Macrolide antibiotics may be recommended for penicillin-allergic patients.

As a rule, relapses or failure to improve should be treated with an antibiotic active against beta-lactamase–producing organisms (eg, a macrolide, a cephalosporin, or amoxicillin-clavulanate). The hypothesis is that colonizing pharyngeal bacteria that produce penicillinase have inactivated penicillin, resulting in treatment failure.

Findings by Hirsh et al report that despite recommendations for amoxicillin or penicillin for treatment of pharyngitis, only 52% of clinicians prescribe the recommended treatment for otitis media, sinusitis, and pharyngitis.^{[14, 15]} A study focusing on inappropriate antibiotic prescriptions by the same team also found that pharyngitis, with 43 antibiotic prescriptions per 1000 population [95% CI, 38-49]), was the third highest diagnosis associated with the most antibiotic prescriptions behind sinusitis and otitis media.^[16]

Corticosteroids (eg, dexamethasone) have been suggested as adjunctive therapy to decrease pain and shorten symptom duration in adults with pharyngitis. A study in children found that a single dose of oral dexamethasone (0.6 mg/kg, not to exceed 10 mg) did not decrease time to onset of clinically significant pain relief or time to complete pain relief.^[11] However, in those children with positive rapid streptococcal test results, there was a statistically significant (but only marginally clinically significant) reduction in time to onset of pain relief.

Therefore, the use of steroids is not routinely recommended but can be considered. This position is also supported by a systematic review of pharyngitis in adult patients, which reported a slight decrease in time to resolution and amount of pain concluded that in view of the heterogeneity of the results, the use of steroids was not routinely recommended but could be offered for consideration on a patient-by-patient basis.^[17]

In addition to adequate antibiotic therapy for patients with GABHS, administer antipyretics for pain and fever in all patients, regardless of whether the cause is bacterial or viral. Ibuprofen (10 mg/kg orally every 8 hours) or acetaminophen (15 mg/kg orally every 4-6 hours) is effective. Any such over-the-counter medications should be taken on a limited basis for a limited time (≤ 2-3 days), in accordance with package insert instructions and recommendations for dosing, delivery, and use; any questions or concerns should be referred to the primary care provider.

For patients with herpangina (stomatitis or pharyngitis), alumina-magnesia mixed with diphenhydramine hydrochloride in a 1:1 ratio can be administered orally before meals to decrease associated discomfort and to help maintain good hydration. This medication can be dosed on the basis of the diphenhydramine component (1.25 mg/kg oral swish and swallow every 6 hours as needed).

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Drainage and Tonsillectomy

For patients with a peritonsillar abscess, needle aspiration and drainage is warranted. Retropharyngeal abscesses often require surgical drainage. An experienced pediatrician can often drain a peritonsillar abscess, but if the pediatrician is uncomfortable with the procedure, referral to an ear, nose, and throat (ENT) specialist or an ED physician is warranted.

If pharyngitis is recurrent or severe, referral to an ENT specialist for possible tonsillectomy may be considered. Parents often request such referrals if their child has had multiple episodes of pharyngitis. It should be pointed out, however, that tonsillectomy generally offers only temporary relief. Although a 50-80% reduction in GABHS pharyngitis is noted during the first 2 years after the procedure, by the third year after tonsillectomy, no difference is reported in comparison with control groups.

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Long-Term Monitoring

Because more than 90% of children clear GABHS from their pharynx within 24 hours after the initiation of antibiotic therapy, they should remain out of school or daycare for 1 day and until fever free. If symptoms persist for longer than 24-48 hours, patients should be reevaluated for the possibility that other concerns may be present, as well as for possible treatment failures.

A study by Schwartz et al reported that all children treated with amoxicillin for strep throat by 5 PM of day 1 may, if afebrile and improved, attend school on day 2.^{[18, 19]}

Follow-up cultures are not routinely necessary unless concerns arise regarding recurrences or carrier states.

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Medication Summary

Penicillin is the typical therapy for group A beta-hemolytic streptococci (GABHS) pharyngitis, in conjunction with prevention of dehydration and supportive care for pain. Many pediatricians prefer amoxicillin oral suspension simply because the taste is much better. Several other antibiotics (eg, macrolides, cephalosporins, amoxicillin-clavulanate) have also been approved to treat GABHS infection. Corticosteroids (eg, oral dexamethasone) have been suggested as an adjunctive therapy; they are not routinely recommended but can be considered.

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Amoxicillin (Moxatag)

• Dosing, Interactions, etc.

Clinical Context:  Amoxicillin is often used in place of penicillin, but it has not been demonstrated to be more effective. Amoxicillin binds to penicillin-binding proteins (PBPs), inhibiting bacterial cell wall growth.

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Azithromycin (Zithromax, Zmax)

• Dosing, Interactions, etc.

Clinical Context:  Azithromycin acts by binding to the 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Nucleic acid synthesis is not affected. The drug concentrates in phagocytes and fibroblasts, as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues.

Azithromycin is used to treat mild-to-moderate microbial infections. The shorter course and once-daily dosing make it a good alternative for patients who are sensitive to penicillin. Pharyngitis-specific dosing should be used.

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Penicillin G benzathine (Bicillin L-A)

• Dosing, Interactions, etc.

Clinical Context:  Penicillin G has been shown to be effective in more than 90% of cases. It binds to PBPs and interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms. Penicillin G is not to be administered intravenously (IV), intra-arterially (IA), or subcutaneously (SC).

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Penicillin VK

• Dosing, Interactions, etc.

Clinical Context:  Penicillin VK is the drug of choice for patients who can tolerate oral therapy. It inhibits the biosynthesis of cell wall mucopeptide. It is bactericidal against sensitive organisms when adequate concentrations are reached and is most effective during the stage of active multiplication. Inadequate concentrations may produce only bacteriostatic effects.

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Erythromycin ethyl succinate (E.E.S, EryPed, Ery-Tab)

• Dosing, Interactions, etc.

Clinical Context:  Erythromycin is recommended by the American Academy of Pediatrics (AAP) for patients who are allergic to penicillin. It binds to the 50S ribosomal subunit of the bacteria, inhibiting protein synthesis. Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes and thus causing RNA-dependent protein synthesis to arrest. It is used for treatment of staphylococcal and streptococcal infections.

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Clindamycin (Cleocin)

• Dosing, Interactions, etc.

Clinical Context:  Clindamycin is a lincosamide used for treatment of serious skin and soft tissue staphylococcal infections. It is also effective against aerobic and anaerobic streptococci (except enterococci) and can be used for recurrent GABHS pharyngitis or in carrier-state cases. Clindamycin inhibits bacterial protein synthesis by its action at the bacterial ribosome; it binds preferentially to the 50S ribosomal subunit and affects the process of peptide chain initiation.

Some prefer this medication when treating disease related to peritonsillar abscesses that have been drained. The capsule should be taken with a full glass of water.

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Rifampin (Rifadin)

• Dosing, Interactions, etc.

Clinical Context:  Rifampin is recommended in conjunction with penicillin for recurrent GABHS infection and for carrier states. The drug inhibits RNA synthesis in bacteria by binding to the beta subunit of DNA-dependent RNA polymerase, which, in turn, blocks RNA transcription; it does not inhibit the mammalian enzyme. It should be taken on an empty stomach.

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Cefuroxime (Ceftin, Zinacef)

• Dosing, Interactions, etc.

Clinical Context:  Cefuroxime is a second-generation cephalosporin that maintains the gram-positive activity of first-generation cephalosporins while adding activity against Proteus mirabilis,Haemophilus influenzae,Escherichia coli,Klebsiella pneumoniae, and Moraxella catarrhalis. It resists degradation by beta-lactamase and is very effective against copathogens. A broad variety of cephalosporins (especially second-generation agents) have been used; however, their ability to prevent rheumatic heart disease is not known.

The oral suspension and the tablets are not bioequivalent and require different dosage regimens. The condition of the patient, the severity of infection, and the susceptibility of the microorganism determine the proper dose and route of administration. The drug should be administered with food to minimize adverse gastrointestinal (GI) effects.

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Ceftriaxone (Rocephin)

• Dosing, Interactions, etc.

Clinical Context:  Ceftriaxone is a third-generation cephalosporin with broad-spectrum gram-negative activity. It arrests bacterial growth by binding to 1 or more PBPs.

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Cefditoren (Spectracef)

• Dosing, Interactions, etc.

Clinical Context:  Cefditoren is a semisynthetic cephalosporin administered as a prodrug. It is hydrolyzed by esterases during absorption and distributed in circulating blood as active cefditoren. Its bactericidal activity results from inhibition of cell wall synthesis via affinity for PBPs.

Cefditoren is indicated for the treatment of acute exacerbation of pharyngitis or tonsillitis caused by susceptible strains of Streptococcus pyogenes. No dose adjustment necessary for mild renal impairment (creatinine clearance 50-80 mL/min/1.73 m²) or mild-to-moderate hepatic impairment.

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Cefixime (Suprax)

• Dosing, Interactions, etc.

Clinical Context:  Cefixime acts by binding to 1 or more of the PBPs. It arrests bacterial cell wall synthesis and inhibits bacterial growth. It should be administered with food to minimize adverse GI effects.

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Cefpodoxime (Vantin)

• Dosing, Interactions, etc.

Clinical Context:  Cefpodoxime is a second-generation cephalosporin that is indicated for the management of infections caused by susceptible mixed aerobic-anaerobic microorganisms. It inhibits bacterial cell wall synthesis by binding to 1 or more of the PBPs. Bacteria eventually lyse because of the ongoing activity of cell-wall autolytic enzymes while cell-wall assembly is arrested.

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Cephalexin (Keflex)

• Dosing, Interactions, etc.

Clinical Context:  Cephalexin is a first-generation cephalosporin that inhibits bacterial replication by inhibiting bacterial cell wall synthesis. It is bactericidal and effective against rapidly growing organisms forming cell walls. Resistance develops through alteration of PBPs.

Cephalexin is effective for treating infections caused by streptococci or staphylococci, including penicillinase-producing staphylococci, and it is at least as effective as erythromycin in eradicating GABHS infection. Cephalexin may be used to initiate therapy when streptococcal or staphylococcal infection is suspected. It is used orally when outpatient management is indicated.

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Cefadroxil

• Dosing, Interactions, etc.

Clinical Context:  Cefadroxil is a first-generation semisynthetic cephalosporin that arrests bacterial growth by inhibiting bacterial cell wall synthesis. It has bactericidal activity against rapidly growing organisms, including S aureus, S pneumoniae, S pyogenes, Moraxella catarrhalis, E coli, Klebsiella species, and Proteus mirabilis.

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Amoxicillin-clavulanate (Augmentin, Amoclan)

• Dosing, Interactions, etc.

Clinical Context:  Amoxicillin-clavulanate is a combination drug that includes an antibiotic and a blocking agent (clavulanic acid). It interferes with the synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.

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Class Summary

Antibiotics are used to treat recurrent GABHS pharyngitis. Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of this clinical setting.

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Dexamethasone (Baycadron)

• Dosing, Interactions, etc.

Clinical Context:  Dexamethasone decreases inflammation by suppressing migration of polymorphonuclear leukocytes (PMNs) and reducing capillary permeability. It possesses many pharmacologic benefits but also has significant adverse effects.

Dexamethasone stabilizes cell and lysosomal membranes, increases surfactant synthesis, increases serum vitamin A concentration, and inhibits prostaglandin and proinflammatory cytokines. The inhibition of chemotactic factors and factors that increase capillary permeability inhibits recruitment of inflammatory cells into affected areas. The drug suppresses lymphocyte proliferation through direct cytolysis, inhibits mitosis, breaks down granulocyte aggregates, and improves pulmonary microcirculation.

Potential adverse effects include hyperglycemia, hypertension, weight loss, GI bleeding or perforation synthesis, cerebral palsy, adrenal suppression, and death. Most of the adverse effects of corticosteroids are dose-dependent or duration-dependent.

Dexamethasone provides symptomatic relief for severe pharyngitis. In this setting, it must be administered in conjunction with antibiotics. Dexamethasone is readily absorbed via the GI tract and metabolized in the liver. Inactive metabolites are excreted via the kidneys. The drug lacks the salt-retaining property of hydrocortisone. Patients can be switched from an IV regimen to an oral regimen in a 1:1 ratio. A single IM dose is convenient and avoids compliance issues.

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Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body’s immune response to diverse stimuli. These agents may be used adjunctively with antibiotics to hasten the onset of pain relief and are especially useful in patients with positive rapid streptococcal antigen test results.

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