Pharyngitis

Pharyngitis is defined as an infection or irritation of the pharynx or tonsils (see the image below). The etiology is usually infectious,
with most cases being of viral origin and most bacterial cases attributable to group A streptococci (GAS). Other causes include
allergy, trauma, toxins, and neoplasia.

Signs and symptoms

It is difficult to distinguish viral and bacterial causes of pharyngitis on the basis of history and physical examination alone.
Nevertheless, the following factors may help rule out or diagnose GAS pharyngitis:

GAS infection is most common in children aged 4-7 years

Sudden onset is consistent with GAS pharyngitis; pharyngitis after several days of coughing or rhinorrhea is more
consistent with a viral etiology
Contact with others who have GAS or rheumatic fever with symptoms consistent with GAS raises the likelihood of GAS
pharyngitis
Headache is consistent with GAS infection
Cough is not usually associated with GAS infection
Vomiting is associated with GAS infection, though not exclusively so
Recent orogenital contact suggests possible gonococcal pharyngitis
A history of rheumatic fever is important
Centor criteria for GAS pharyngitis include the following:

Fever (1 point)
Anterior cervical lymphadenopathy (1 point)
Tonsillar exudate (1 point)
Absence of cough (1 point)
A score of 0-1 makes GAS infection unlikely; a score of 4 makes it likely. In adults, the positive predictive value of these criteria is
around 40% if 3 criteria are met and about 50% if 4 criteria are met.

Diagnosis
Laboratory studies that may be helpful include the following:

Group A beta-hemolytic streptococcal rapid antigen detection test (preferred diagnostic method in
emergency settings)
Throat culture (criterion standard for diagnosis of GAS infection [90-99% sensitive])
Mono spot (up to 95% sensitive in children; less than 60% sensitive in infants)
Peripheral smear
Gonococcal culture if indicated by the history

Imaging studies generally are not indicated for uncomplicated viral or streptococcal pharyngitis. However, the
following may be considered:

Lateral neck film in patients with suspected epiglottitis or airway compromise

Soft-tissue neck CT if concern for abscess or deep-space infection exists

Management
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 measures may include the following:

Assess and secure the airway, if necessary

Assess the patient for signs of toxicity, epiglottitis, or oropharyngeal abscess
Evaluate hydration status, and rehydrate as necessary
Assess for GAS infection if clinically suspected
Most cases, whether viral or bacterial, are relatively benign and self-limited. Management of GAS infection, when indicated, includes
the following:

Do not treat patients without a positive culture or positive rapid antigen detection test result
Perform a rapid antigen detection test if GAS is clinically suspected on the basis of the history and physical examination; if
test results are positive, begin antibiotic therapy
Patients who are positive for all 4 Centor criteria can often be treated with antibiotics without antigen testing or cultures
Household contacts of patients with GAS infection or scarlet fever should be treated for a full 10 days of antibiotics without
testing only if they have symptoms consistent with GAS; asymptomatic contacts should not be treated
If the diagnosis is in doubt or the above criteria are not met, initiation of antibiotic therapy should await rapid antigen test
or culture results

Background
Pharyngitis is defined as an infection or irritation of the pharynx and/or tonsils. The etiology is usually infectious, with most cases
being of viral origin. These cases are benign and self-limiting for the most part. Bacterial causes of pharyngitis are also self-limiting,
but are concerning because of suppurative and nonsuppurative complications. Other causes include allergy, trauma, toxins, and
neoplasia.[1]
The most significant bacterial agent causing pharyngitis in both adults and children is GAS infection (Streptococcus pyogenes);

Pathophysiology
With infectious pharyngitis, bacteria or viruses may directly invade the pharyngeal mucosa, causing a local inflammatory response.
Other viruses, such as rhinovirus and coronavirus, can cause irritation of pharyngeal mucosa secondary to nasal secretions.[2]
Streptococcal infections are characterized by local invasion and release of extracellular toxins and proteases. In addition, M protein
fragments of certain serotypes of GAS are similar to myocardial sarcolemma antigens and are linked to rheumatic fever and
subsequent heart valve damage. The prevalence rates of these serotypes of GAS have been becoming rarer over the past several
years. Acute glomerulonephritis may result from antibody-antigen complex deposition in glomeruli.[3]

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 GAS infection (Streptococcus pyogenes), and the most common viruses are rhinovirus and adenovirus. GAS is most
prevalent in late fall through early spring.

Age
Pharyngitis occurs with much greater frequency in the pediatric population. Approximately 15-30% of pharyngitis cases among
school-aged children in the cooler months are due to GAS. Only 10% of adult cases of pharyngitis are due to GAS.[1]

The peak incidence of bacterial and viral pharyngitis occurs in the school-aged child aged 4-7 years.
Pharyngitis, especially GAS infection, is rare in children younger than 3 years.
Mycoplasma pneumoniae, Chlamydia pneumoniae, and Arcanobacterium haemolyticus are other bacterial causes of
pharyngitis, but these pathogens are rare. Antibiotics covering atypical pathogens should not routinely be used to treat pharyngitis.

History
Viral and bacterial causes of pharyngitis are similar, and the differentiation of the etiology is difficult based on history and physical
examination alone. Signs and symptoms alone cannot be used to rule out or diagnose GAS pharyngitis. [7] Despite this, classic
presentations are described below.

GAS infection is most common in children aged 4-7 years.

Sudden onset is consistent with a GAS 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 GAS or rheumatic fever presenting with symptoms consistent with
GAS are more likely to have GAS pharyngitis.
Headache is consistent with GAS infection.
Cough is not usually associated with GAS infection.
Vomiting is associated with GAS 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.

The Centor criteria have been used in the past as a way to diagnose and treat GAS pharyngitis. [8] These include the
following:

Fever
Anterior cervical lymphadenopathy
Tonsillar exudate
Absence of cough
One point is awarded for each of the criteria met, with patients scoring 0-1 unlikely to have GAS infection and patients with
a score of 4 more likely to have GAS.
In adults, the positive predictive value of the Centor criteria for predicting GAS pharyngitis is around 40% if 3 criteria are met, and
about 50% if 4 criteria are met.[10] These criteria along with other clinical features should be used to guide treatment for pharyngitis
in adults.

Physical
See the list below:

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.
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 GAS 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.
o
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, whereas
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
o
A sandpapery scarlatiniform rash is seen in GAS infection (see Scarlet Fever).[11]
o
Maculopapular rashes are seen with various viral infections and with infectious mononucleosis empirically
treated with penicillin.
o
o
o
o
o

Diagnostic Considerations
These include the following:

Allergic rhinitis with postnasal drip

Airway obstruction
Head and neck neoplasias
Gastroesophageal reflux disease (GERD)
Peritonsillar cellulitis

Differential Diagnoses

Candidiasis in Emergency Medicine

Diphtheria

Emergent Management of Croup (Laryngotracheobronchitis)

Emergent Management of Gonorrhea

Emergent Management of Pediatric Epiglottitis

Epiglottitis

Hand-Foot-and-Mouth Disease in Emergency Medicine

Herpes Simplex in Emergency Medicine

Mononucleosis in Emergency Medicine

Pediatric Pharyngitis

Peritonsillar Abscess in Emergency Medicine

Pharyngitis

Pneumonia, Mycoplasma

Retropharyngeal Abscess

Rheumatic Fever in Emergency Medicine

Scarlet Fever

Workup
See the list below:

o
o
o
o
o

GABHS rapid antigen detection test

See the list below:
This is the preferred method for diagnosing GAS infection in the emergency department because of difficulties with culture
follow-up.
Only patients with a high clinical likelihood of GAS pharyngitis should be tested. Patients with a Centor score of 0-1 should
be treated symptomatically without testing.[13]
Antigens are specific, but sensitivities vary. Children with a negative antigen test should have a follow-up culture unless
the antigen being used in the office has been shown to be as sensitive as a culture.[11]
The use of a GABHS rapid antigen detection test can decrease the use of unnecessary antibiotics in pediatric patients
when used properly.[14]
Adults do not need follow-up culture after a negative antigen test because of the low incidence of GAS in this population.

Throat culture
o
o

This is the criterion standard for diagnosis of GAS infection (90-99% sensitive). Although less expensive than the rapid
antigen detection test, it is not be the best test to use in the emergency department because of difficulty with follow-up. The
guidelines that recommend cultures for GAS screening are aimed at office-based practices and not the emergency department.
Patients can be treated up to 9 days after onset of symptoms to prevent acute rheumatic fever, so immediate antibiotic
therapy is not crucial if patients can be easily contacted for follow-up should a culture become positive. [1]
o
Mono spot is up to 95% sensitive in children (less than 60% sensitivity in infants).
o
Peripheral smear may show atypical lymphocytes in infectious mononucleosis. [2]
o
Perform gonococcal culture as indicated by history.
o
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
See the list below:

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 can be used if concern for abscess or deep-space infection exists; however, peritonsillar abscess is
almost always a clinical diagnosis. Imaging is rarely needed for diagnosis.

Procedures
See the list below:

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).

Prehospital Care
See the list below:

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

See the list below:

Assess and secure the airway, if necessary.

Assess the patient for signs of toxicity, epiglottitis, or oropharyngeal abscess.[16]
Evaluate the hydration status because severe pharyngitis limits oral intake. Appropriate measures to rehydrate should be
initiated, including intravenous hydration.

Assess for GAS infection if clinically suspected. A suggested algorithm as is follows.

o
In general, patients should not be treated without a positive culture or positive rapid antigen detection test result
because of increasing antibiotic resistance. Guidelines from the Infectious Diseases Society of America (IDSA) and American
Heart Association state that microbiologic confirmation (via a rapid antigen test or culture) is required for the diagnosis of GAS. [9,
5]

o
o
o
o

Perform rapid antigen detection test if GAS 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 GAS as the etiology (Centor score 0-1).
Patients who are positive for all 4 Centor criteria can often be treated with antibiotics without antigen testing or
cultures.
Household contacts of patients with GAS infection or scarlet fever should be treated for a full 10 days of
antibiotics without testing only if they have symptoms consistent with GAS. [5] Asymptomatic contacts should not be treated.
If clinically doubtful or the above criteria are not met, it is best to await rapid antigen or culture results to initiate
antibiotic therapy

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.[18] 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.
[19]
Antibiotics do not prevent acute glomerulonephritis. Steroids may be used for airway compromise and
symptomatic relief.[20] 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.

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.

[24, 25]

Some support the use of cephalosporins instead of penicillin as first-line therapy for GAS.
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.
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.
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.

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.

Dosing & Uses

Adult

Dosage Forms & Strengths

Ear, Nose, & Throat Infections
Mild to moderate infections

500 mg PO q12hr or 250 mg PO q8hr for 10-14 days

Severe infections

875 mg PO q12hr or 500 mg PO q8hr for 10-14 days

Tonsillitis/pharyngitis

Moxatag: 775 mg PO qDay for 10 days, taken within 1 hour after finishing a meal
Spectrum of action

- and -hemolytic Strep, S pneumoniae, Staph spp, H influenzae

Genitourinary Tract Infections

Mild to moderate infections

500 mg PO q12hr or 250 mg PO q8hr

Severe infections

875 mg PO q12hr or 500 mg PO q8hr

Spectrum of action

E coli, P mirabilis, or E faecalis

Skin & Skin Structure Infections

Mild to moderate infections

500 mg PO q12hr or 250 mg PO q8hr

Severe infections

875 mg PO q12hr or 500 mg PO q8hr

Spectrum of action

- and -hemolytic Strep, Staph spp, E coli

Tonsilitis
775 mg (ER tabs) PO qDay for 10 days

Lower Respiratory Tract Infections

875 mg PO q12hr or 500 mg PO q8hr for 10-14 days
Spectrum of action

- and -hemolytic Strep, S pneumoniae, Staph spp, H influenzae

Helicobacter Pylori
H pylori infection and active or 1-year history of duodenal ulcer
Triple therapy

1 g PO q12hr for 14 days with lansoprazole (30 mg) and clarithromycin (500 mg)
Dual therapy

1 g PO q8hr for 14 days with lansoprazole (30 mg) in patients intolerant of, or resistant to, clarithromycin

Anthrax
Postexposure inhalational prophylaxis

500 mg PO q8hr

Infective Endocarditis
Prophylaxis
2 g PO 30-60 min before procedure
Dosing considerations

AHA guidelines recommend prophylaxis only in high-risk patients undergoing invasive procedures who have a history of cardiac conditions
that predispose them to a risk of infection

Lyme Disease (Off-label)

Erythema migrans and other symptoms of early dissemination
500 mg PO q8hr (depending on size of patient) for 3-4wk
50 mg/kg/day q8hr in divided doses; maximum 500 mg/dose

Chlamydial Infection in Pregnant Women (Off-label)

First trimester: 500 mg PO q8hr for 7 days
Dosing considerations

First trimester: Test to document chlamydial eradication and retest for infection 3 months after treatment
Second or third trimester: Test to document chlamydial eradication

Administration
Take without regard to meals

Dosing Modifications
Renal impairment: Patients with impaired renal function do not generally require dose reduction unless impairment is severe; do not administer
extended-release product in patients with CrCl <30 mL/min
GFR <30 mL/min: Should not receive 875 mg (immediate release) or 775 mg (extended release)
GFR 10-30 mL/min: 250-500 mg q12hr, depending on severity of infection
GFR <10 mL/min: 250-500 mg q24hr depending on severity of infection
Hemodialysis patients: 250-500 mg q24hr, depending on severity of infection; patients should receive additional dose during and at completion of
dialysis; do not administer extended-release product or 875 mg immediate release

Pediatric

Dosage Forms & Strengths

Ear, Nose, & Throat Infections
Mild to moderate infections

<3 months: 30 mg/kg/day PO divided q12hr for 48-72 hours; for 10 days for S pyogenes infections
>3 months and <40 kg: 25 mg/kg/day PO divided q12hr or 20 mg/kg/day PO divided q8hr
>40 kg: 500 mg PO q12hr or 250 mg PO q8hr for 10-14 days
Severe infections

<3 months: 30 mg/kg/day PO divided q12hr for 48-72 hours; for 10 days for S pyogenes infections
>3 months and <40 kg: 45 mg/kg/day PO divided q12hr or 40 mg/kg/day PO divided q8hr
>40 kg: 875 mg PO q12hr or 500 mg PO q8hr for 10-14 days
Tonsillitis/Streptococcal pharyngitis

50 mg/kg PO qDay for 10 days, not to exceed 1 g/day, OR 25 mg/kg PO BID for 10 days, not to exceed 500 mg/dose
>12 years: 775 mg (Moxatag) PO qDay for 10 days, taken within 1 hour after meal (swallow tablet whole; do not crush or chew)
Spectrum of action

- and -hemolytic Streptococcus, S pneumoniae, Staphylococcus, H influenzae

Acute Otitis Media

>3 months and <40kg: 80-90 mg/kg/day PO divided q8-12hr
>40 kg: 500 mg PO q12hr or 250 mg PO q8hr for 10-14 days

Lower Respiratory Tract Infections

Mild, moderate, or severe infections

<3 months: 30 mg/kg/day PO divided q12hr for 48-72 hours; for 10 days for S pyogenes infections
>3 months and <40 kg: 45 mg/kg/day PO divided q12hr or 40 mg/kg/day PO divided q8hr
>40kg: 875 mg PO q12hr or 500 mg PO q8hr for 10-14 days
Spectrum of action

- and -hemolytic Streptococcus, S pneumoniae, Staphylococcus, H influenzae

Anthrax
Postexposure inhalational prophylaxis
<40 kg: 15 mg/kg PO q8hr (minimum recommended dose; should not be <45 mg/kg/day or >q8hr
>40 kg: 500 mg PO q8hr
80 mg/kg/day PO divided q8hr for 4 weeks (with concomitant vaccine) or for 60 days (without vaccine)

Infective Endocarditis
Prophylaxis
50 mg/kg PO 30-60 min before procedure
Dosing considerations

AHA guidelines recommend prophylaxis only in high-risk patients undergoing invasive procedures with history of cardiac conditions that
predispose them to infection

Lyme Disease
Erythema migrans and other symptoms of early dissemination
<3 months: Safety and efficacy not established
>3 months and 40 kg: 25-50 mg/kg/day divided q8hr; not to exceed 500 mg

Administration
Take without regard to meals
Mixing oral suspension: Tap bottle until all powder flows freely; add approximately one third of the total amount of water for reconstitution and shake
vigorously to wet powder; add remainder of water and shake vigorously again
After reconstitution, place required amount of suspension directly on childs tongue for swallowing; if taste is unacceptable, required amount of
suspension can be added to formula, milk, fruit juice, water, ginger ale, or other cold drinks; preparation must be taken immediately
Shake suspension well before using; any unused portion must be discarded after 14 days

Pregnancy & Lactation

Pregnancy category: B
Lactation: Excreted in breast milk, use caution

Mechanism of Action
Derivative of ampicillin and has similar antibacterial spectrum (certain gram-positive and gram-negative organisms); similar bactericidal action as
penicillin; acts on susceptible bacteria during multiplication stage by inhibiting cell wall mucopeptide biosynthesis; superior bioavailability and stability to
gastric acid and has broader spectrum of activity than penicillin; less active than penicillin against Streptococcus pneumococcus; penicillin-resistant
strains also resistant to amoxicillin, but higher doses may be effective; more effective against gram-negative organisms (eg, N meningitidis, H
influenzae) than penicillin

Absorption
Rapidly absorbed
Bioavailability: 74-92%
Peak plasma time: 2hr (capsule); 3.1 hr (extended release tab); 1 hr (suspension)

Distribution
Most body fluids and bone, CSF <1%
Protein bound: 17-20%

Metabolism
Hepatic

Elimination
Excretion: Urine
Half-life: 3.7 hr (full-term neonates); 1-2 hr (infants and children); 0.7-1.4 hr (adults)

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.

Adult

Dosage Forms & Strengths

Genitourinary Tract Infections
250 mg PO q6hr; dosage range, 1-4 g/day in divided doses

Bone Infections
250 mg PO q6hr; dosage range, 1-4 g/day in divided doses

Uncomplicated Cystitis
250 mg PO q6hr or 500 mg PO q12hr; dosage range, 1-4 g/day in divided doses

Otitis Media
250 mg PO q6hr; dosage range, 1-4 g/day in divided doses

Skin/Skin Structure Infections

250 mg PO q6hr or 500 mg PO q12hr; dosage range, 1-4 g/day in divided doses

Respiratory Tract Infections

250 mg PO q6hr; dosage range, 1-4 g/day in divided doses

Streptococcal Pharyngitis
250 mg PO q6hr or 500 mg PO q12hr; dosage range, 1-4 g/day in divided doses

Cellulitis and Mastitis

500 mg PO q6hr; dosage range, 1-4 g/day in divided doses

Renal Impairment
CrCl <10 mL/min: 250-500 mg PO q12-24hr
CrCl 10-50 mL/min: 500 mg PO q8-12hr

Hepatic Impairment
Not studied

Dosing Considerations
Susceptible organisms

Haemophilus influenzae, Klebsiella spp, Moraxella catarrhalis, Proteus mirabilis, staphlococcus, group A beta-hemolytic streptococcus

Pediatric

Dosage Forms & Strengths

Uncomplicated Cystitis

<15 years: 25-50 mg/kg/day PO divided q6-8hr for 10 days; not to exceed 4 g/day

>15 years: 250 mg PO q6hr; dosage range, 1-4 g/day in divided doses

Genitourinary Tract Infections

25-50 mg/kg/day PO divided q6-8hr for 10 days; not to exceed 4 g/day

Beta-Hemolytic Streptococcal Infections

25-50 mg/kg/day PO divided q6-8hr for 10 days; not to exceed 4 g/day

Bone Infections

25-50 mg/kg/day PO divided q6-8hr for 10 days; not to exceed 4 g/day

Otitis Media

75-100 mg/kg/day PO divided q6hr for 10 days; not to exceed 4 g/day

Skin/Skin Structure Infections

25-50 mg/kg/day PO divided q6-8hr for 10 days; not to exceed 4 g/day

Respiratory Tract Infections

25-50 mg/kg/day PO divided q6-8hr for 10 days; not to exceed 4 g/day

Streptococcal Pharyngitis

25-50 mg/kg PO q12hr for 10 days; not to exceed 500 mg q12hr

Cellulitis and Mastitis

Adolescents: 500 mg PO q6hr; dosage range, 1-4 g/day in divided doses

Pregnancy & Lactation

Pregnancy category: B
Lactation: Drug excreted in breast milk; use with caution

Pharmacology
Mechanism of Action
Binds to one or more of the penicillin binding proteins, which in turn inhibits synthesis of bacterial cell wall

Absorption
Bioavailability: 90%; absorption delayed in young children
Peak serum time: 1 hr
Peak plasma concentration: 10-18 mcg/mL (500-mg dose)

Distribution
Distributed widely into most tissues and fluids; penetrates CSF poorly
Protein bound: 6-15%

Metabolism
Minimally metabolized in liver

Elimination
Half-life: 0.5-1.2 hr

Excretion: Urine (80-100% as unchanged drug)

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.

Adult
Dosage Forms & Strengths
Acute Bacterial Exacerbations of Chronic Obstructive Pulmonary Disease
500 mg PO once, then 250 mg once daily for 4 days
Alternatively, 500 mg PO qDay for 3 days

Acute Otitis Media

500 mg PO once, then 250 mg once daily for 4 days

Genital Ulcer Disease (Chancroid)

1 g PO once

Acute Bacterial Sinusitis

500 mg/day PO for 3 days or 2 g PO once

Community-Acquired Pneumonia
500 mg PO once, then 250 mg once daily for 4 days
2 g extended release suspension PO once
500 mg IV as single dose for at least 2 days; follow with oral therapy with single dose of 500 mg to complete 7-10 days course of therapy

Pharyngitis/Tonsillitis
500 mg PO once, then 250 mg once daily for 4 days
Alternatively, 12 mg/kg PO; not to exceed 500 mg on day 1 followed by 6 mg/kg; not to exceed 250 mg on days 2 through 5

Uncomplicated Skin/Skin Structure Infections

500 mg PO once, then 250 mg once daily for 4 days

Cat Scratch Disease

>45.5 kg: 500 mg PO once, then 250 mg once daily for 4 days

Pertussis (Off-label)
500 mg PO once, then 250 mg once daily for 4 days

Acute Pelvic Inflammatory Disease

500 mg IV over 1 hour once daily for 1-2 days; follow therapy by oral route with 250 mg qDay for 5 days to complete a 7 day therapy

Uncomplicated Gonococcal Infections

Infection of pharynx, cervix, urethra, or rectum: Ceftriaxone 250 mg IM once plus azithromycin 1 g PO once (preferred) or alternatively doxycycline 100
mg PO q12hr for 7 days
CDC STD guidelines: MMWR Recomm Rep. June 5, 2015:64(RR3);1-137
Sexual assault

Prophylaxis of sexually transmitted diseases (STDs) such as gonorrhea after sexual assault per CDC guidelines includes the following 3drug regimen:
Ceftriaxone 250 mg IM once PLUS
Azithromycin 1 g PO once PLUS
Metronidazole or tinidazole 2 g PO once
If alcohol has been recently ingested or emergency contraception is provided, metronidazole or tinidazole can be taken by the victim at
home rather than as directly observed therapy to avoid drug interactions

Mycobacterium Avium Complex Infection

Prevention

Primary prophylaxis: 1.2 g PO once weekly or 600 mg PO twice weekly; with or without rifabutin 300 mg once daily
Secondary prophylaxis: 500-600 mg PO qDay in combination with ethambutol

Treatment

250 mg PO once daily in combination with ethambutol 15 mg/kg/day with or without rifabutin 300 mg/day
Alternative regimen: 500 mg PO 3 times weekly in combination with ethambutol 15 mg/kg/day with or without rifabutin 300 mg/day

Endocarditis (Off-label)
Prophylaxis
500 mg PO 30-60 min before procedure
Current American Heart Association (AHA) guidelines recommend only for high-risk patients

Dosing Considerations
Not for use in patients with pneumonia judged to be inappropriate for oral therapy because of moderate to severe illness or risk factors
Susceptible organisms

Actinobacillus actinomycetemcomitans, Actinomyces israelii, Actinomyces naeslundii, Actinomyces odontolyticus, Afipia felis, Arachnia
propionica, Arcanobacterium (Corynebacterium) haemolyticum, Bartonella henselae, Bartonella quintana, Bordetella pertussis, Borrelia burgdorferi,
Borrelia recurrentis, Klebsiella granulomatis, Campylobacter jejuni, Chlamydia pneumoniae (TWAR agent), Chlamydia trachomatis, Haemophilus
ducreyi, Haemophilus influenzae, Legionella spp, Mycobacterium simiae, Mycobacterium scrofulaceum, Mycobacterium xenopi, Mycoplasma
pneumoniae, Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae, Staphylococcus aureus, Streptococcus (group C and G), Streptococcus
agalactiae (group B), Streptococcus bovis (group D), Streptococcus intermedius group (Streptococcus anginosus, Streptococcus intermedius,
Streptococcus constellatus), Streptococcus pneumoniae, Streptococcus pyogenes (group A), viridans streptococci
First-line therapy: A felis, B henselae, B quintana, B pertussis, C jejuni, C pneumoniae (TWAR agent), C trachomatis, H ducreyi, H
influenzae, Legionella spp, M scrofulaceum, M simiae, M xenopi, N gonorrhoeae

Pediatric

Dosage Forms & Strengths

Acute Otitis Media

<6 months: Safety and efficacy not established

6 months: 30 mg/kg of oral suspension once or 10 mg/kg PO once daily for 3 days or 10 mg/kg once on day 1 followed by 5 mg/kg on
days 2-5

Community-Acquired Pneumonia

<6 months: Safety and efficacy not established

6 months: 10 mg/kg PO on day 1, followed by 5 mg/kg PO on days 2 through 5

6 months (Zmax): 60 mg/kg PO once; not to exceed 2 g

Cat Scratch Disease (Off-label)

<45.5 kg: 10 mg/kg PO as single dose; then 5 mg/kg PO qDay on days 2 through 5

>45.5 kg: 500 mg PO once, then 250 mg once daily for 4 days

Acute Bacterial Sinusitis

Zmax: 2g PO once

10 mg/kg of oral suspension PO once daily for 3 days

Pharyngitis/Tonsillitis

<2 years: Safety and efficacy not established

2 years: 12 mg/kg PO once daily for 5 days; not to exceed 500 mg/day

Chlamydia Trachomatis Infection (Off-label)

>45 mg/kg: 1 g PO as single dose

Mycobacterium Avium Complex Infection

Prophylaxis

<6 years: Safety and efficacy not established

6 years primary prophylaxis: 20 mg/kg PO once weekly; not to exceed 1200 mg or 5mg/kg/day qDay; not to exceed 250 mg/day

6 years secondary prophylaxis: 5 mg/kg/day PO qDay; not to exceed 250 mg/day in cimbination with ethambutol with or without rifabutin

Treatment: 10-12 mg/kg/day PO; not to exceed 500 mg; used in combination with ethambutol; if severe disease patient should also receive
rifabutin

Pregnancy & Lactation

Pregnancy category: B
Lactation: Unknown whether drug is excreted into breast milk; use with caution

Pharmacology
Mechanism of Action
Binds to 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent
protein synthesis to arrest; does not affect nucleic acid synthesis
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

Absorption
Rapidly absorbed
Bioavailability: 37%; variable effect with food (increased with oral suspension, unchanged with tablet)
Peak serum time: 2-3 hr (immediate release); 5 hr (extended release)

Distribution
Extensively distributed into skin, lungs, sputum, tonsils, and cervix; penetrates cerebrospinal fluid (CSF) poorly
Protein bound: 7-50% (concentration dependent)
Vd: 33.3 L/kg (PO); 31.1 L/kg (IV)

Metabolism

Metabolized in liver

Elimination
Half-life: ~70 hr (immediate release); 59 hr (extended release)
Excretion: Feces (50% as unchanged drug), urine (5-12%)

Administration
IV Incompatibilities
Y-site: Amikacin, aztreonam, cefotaxime, ceftazidime, ceftriaxone, cefuroxime, ciprofloxacin, clindamycin, droperidol, famotidine, fentanyl, furosemide,
gentamicin, imipenem, cilastatin, ketorolac, levofloxacin, morphine, piperacillin-tazobactam, ondansetron(?), potassium chloride, ticarcillin-clavulanate,
tobramycin

IV Compatibilities
Solution (partial list): SWI, D5W, LR, D5/LR, D5/NS, NS, NS
Y-site: Bivalirudin, dexmedetomidine, diphenhydramine, dolasetron, droperidol

IV Preparation
Dilute 500-mg vial in 4.8 mL of SWI (100 mg/mL)
Dilute further in NS to 1 mg/mL (500 mL) or 2 mg/mL (250 mL)

IV Administration
Use standard syringe
1 mg/mL solution: Infuse over 3 hours
2 mg/mL solution: Infuse over 1 hour

Oral Administration
Tablet: Take tablets without regard to food; however, food may enhance tolerability
Oral suspension

Conventional oral suspension (100 mg/5 mL, 200 mg/5 mL) may be stored for 10 days after reconstitution and taken without regard to food
Conventional 1 g package must be taken immediately after reconstitution
Extended-release oral suspension must be taken on empty stomach within 12 hours of reconstitution; given only in single dose; not
interchangeable with immediate release formulation

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.

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.
[30]
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.[31, 32] They should be used selectively for patients with significant swelling or odynophagia.

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.

Follow-up
Further Outpatient Care
See the list below:

o
o
o
o

Follow-up for GAS pharyngitis

A standardized protocol needs to be established at each institution or ED to ensure follow-up for patients with pending throat
cultures. This 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. [1]
A follow-up culture should be taken if history or evidence of rheumatic fever or if symptoms are consistent with a relapse. [26]
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.[11]
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.

Further Inpatient Care

See the list below:

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

Transfer
See the list below:

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
See the list below:

Throat cultures should be obtained on close contacts of patients with a history of a nonsuppurative complication (acute rheumatic fever) of
a streptococcal infection or if recurrent outbreaks of GAS pharyngitis occur.[5]
Diphtheria immunization is highly effective and recommended for nonimmunized patients to reduce potential morbidity and mortality of the
disease.

Complications
See the list below:

General complications of pharyngitis (mainly seen in cases of bacterial pharyngitis) include sinusitis, otitis media, epiglottitis, mastoiditis,
and pneumonia.
Suppurative complications of bacterial pharyngitis result from spread of infection from pharyngeal mucosa via hematogenous,
lymphatic, or direct extension (more common with GAS); peritonsillar abscess; retropharyngeal abscess; or suppurative cervical lymphadenitis. It is
unclear if antibiotic therapy can prevent these complications as abscess isolates are often polymicrobial. Many experts believe these are actually
independent entities and not related to GAS pharyngitis.
In addition to the above general complications, nonsuppurative complications (3% incidence) specific to GAS 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-Barr
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. [11]

Prognosis
See the list below:

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. [4]Of note, GAS resistance to penicillin is NOT thought to be a
reason for treatment failures with penicillin.

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. It should be noted that pain medications and steroid use for pharyngitis are
extremely effective for improving symptoms of pharyngitis. [19]

Patient Education
See the list below:

o
o

Patients must be instructed to complete the full course of antibiotic therapy, as improvement may occur rapidly.
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 patient education resources, see the Infections Center. Also see the patient education articles Sore Throat and Mononucleosis.