Therapeutics

Upper Respiratory Tract

Infection Dr Sura Al Zoubi

PhD,

MClinPharm

Lecture 19

1

References

• Pharmacotherapy: A Pathophysiologic

Approach, 11e. Chapter 126: Upper Respiratory

Tract Infections

2

URTI

• Acute Otitis media

• Acute Bacterial Rhinosinusitis

• Acute Pharyngitis

ACUTE OTITIS MEDIA

• Otitis media is an inflammation of the middle ear.

• There are three subtypes of otitis media: acute otitis media, otitis media with effusion, and chronic otitis media.

• Acute otitis media is the subtype with the greatest role for antibiotics.

• It is one of the leading reasons for physicians’ office visits and emergency department visits. half of cases occur in children under 5 years of age

• Common bacterial pathogens include Streptococcus pneumoniae (S. pneumoniae), nontypeable Haemophilus influenzae (H. influenzae), and Moraxella catarrhalis (M. catarrhalis). all can possess resistance to β-lactams

Pathophysiology (otitis media)

• Acute otitis media usually follows a viral upper respiratory tract infection that impairs the mucociliary apparatus and causes Eustachian tube dysfunction in the middle ear

• In otitis media, the middle ear becomes blocked with fluid, resulting in a bulging and erythematous tympanic membrane.

• Bacteria that colonize the nasopharynx enter the middle ear and are not cleared properly by the mucociliary system.

• The bacteria proliferate and cause infection.

CLINICAL PRESENTATION (otitis media)

• General

• Cases of acute otitis media often follow viral upper respiratory tract infections. Nonverbal children with ear pain might hold, rub, or tug their ear. Infants might cry, be irritable, or have difficulty sleeping.

• Signs and Symptoms

• Bulging of the tympanic membrane

• Otorrhea

• Otalgia (considered to be moderate or severe if pain lasts at least 48 hours)

• Fever (considered to be severe if temperature is 39°C or higher)

Treatment

• Treatment goals include pain management and prudent antibiotic use. It is important to consider primary prevention of acute otitis media through the use of bacterial and viral vaccines. (why viral?)

• The first step in treatment is to differentiate acute otitis media from otitis media with effusion or chronic otitis media

• Amoxicillin is the mainstay of therapy and that penicillin resistance can be overcome, in many cases, with higher doses of amoxicillin.

• The therapeutic strategy should be changed if complications develop or if symptoms fail to resolve within 3 days

Nonpharmacologic Therapy

• Children with acute otitis media should be assessed for pain.

• Those with pain should be offered treatment to reduce pain regardless of the decision to administer antibiotics because antibiotics do not reduce pain in the first 24 hours.

• Choice of pain treatment depends on possible benefits and risks to the individual patient.

• Acetaminophen and ibuprofen are mainstays of treatment, are effective analgesics for mild-to-moderate pain, and are readily available.

• Eardrops with a local anesthetic may offer additional, but brief, benefit over acetaminophen in patients at least 5 years of age

Pharmacological Therapy

• The decision to administer antibiotics depends on patient age, symptom severity, laterality, and joint decision-making with parents/caregivers.

• Children who should receive antibiotics are:

1. 6 months to 12 years of age, with moderate-to-severe ear pain or temperature of 39°C or higher

2. 6 to 23 months of age, with nonsevere bilateral acute otitis media

• Antibiotics or observation without antibiotics (watchful waiting) may be considered in:

1. Children 6 to 23 months, with nonsevere unilateral acute otitis media

2. Children 24 months to 12 years of age, with nonsevere acute otitis media

• If antibiotics are to be administered, then amoxicillin should be given to most children.

• Exceptions include children who:

1. have received amoxicillin in the last 30 days,

2. have concurrent purulent conjunctivitis,

3. have a history of recurrent infection unresponsive to amoxicillin.

• These patients should receive amoxicillin-clavulanate instead of amoxicillin.

• Clinicians should reassess the plan if the child’s symptoms worsen or decline within 48 to 72 hours of symptom onset

Pharmacological Therapy

• Amoxicillin has a long record of safety, possesses a narrow spectrum of activity, is inexpensive, and is more palatable than other options. Higher middle ear fluid concentrations of amoxicillin, as a result of higher dosing, overcome most drug-resistant S.pneumoniae

• Cephalosporins are expensive, have an increased incidence of side effects, and may increase selective pressure for resistant bacteria. Furthermore, most cephalosporins do not achieve adequate middle ear fluid concentrations against drug-resistant S. pneumoniae for the desired duration of the dosing interval.

• Use of trimethoprim-sulfamethoxazole and erythromycin-sulfisoxazole is discouraged because of high rates of resistance

• Although single doses of ceftriaxone have been used, daily doses for 3 days are recommended to optimize clinical outcomes

• Macrolides are not recommended because they lack efficacy against both H. influenzae and S. pneumoniae

Pharmacological Therapy

• Tympanocentesis can also be considered for treatment failure or persistent acute otitis

media. It relieves pain and pressure and can be used to collect fluid to identify the causative

agent.

• There is ongoing debate regarding the optimal duration of therapy for acute otitis media.

Traditional recommendations call for 10 days of antibiotic therapy; however, some experts

have speculated that patients can be treated for as little as 5 to 7 days. Unfortunately,

evidence does not support this practice in children.

• Short-course treatment is not recommended in children younger than 2 years of age.

• Recurrent acute otitis media (three episodes in 6

months or four episodes in 1 year with one

episode in the preceding 6 months) is of

concern because children younger than 3 years

of age are at high risk for hearing loss and

language and learning disabilities.

• Clinicians should not prescribe antibiotics as

prophylaxis against recurrent episodes, but they

may offer tympanostomy tubes (T tubes).

Evaluation of Therapeutic Outcomes

• Procalcitonin increases in response to bacterial infection and declines as the infection resolves.

• Clinicians are starting to use procalcitonin blood levels to decide when to initiate and discontinue antibiotics in patients with acute upper respiratory infections (URIs).

• Procalcitonin protocols significantly reduced antibiotic consumption without negatively impacting patient survival or treatment failure. However, there are still several aspects of procalcitonin monitoring that need to be resolved, including the timing of levels, the procalcitonin cutoff values for different clinical decision points, and the cost-effectiveness of this technology

• Patients with acute otitis media should be reassessed after 48 to 72 hours. By this time, there should be clinical improvement in the signs and symptoms of infection, including pain, fever, and erythema/bulging of the tympanic membrane

• Complications of otitis media are infrequent but include mastoiditis, bacteremia, meningitis, and auditory sequelae with the potential for speech and language impairment

ACUTE BACTERIAL

RHINOSINUSITIS

• Sinusitis is an inflammation and/or infection of the paranasal sinuses, or membrane-lined air spaces, around the nose.

• Even though the majority of rhinosinusitis infections are viral in origin, antibiotics are frequently prescribed. It is thus important to differentiate between viral and bacterial rhinosinusitis to avoid antibiotic overuse.

• Acute bacterial rhinosinusitis is over-diagnosed; thus, antibiotics are overprescribed.

• Acute bacterial rhinosinusitis is caused, most often, by S. pneumoniae, H. influenzae and M. catarrhalis.

• Acute bacterial rhinosinusitis is often preceded by a viral respiratory tract infection that causes mucosal inflammation. This can lead to obstruction of the sinus ostia—the pathways that drain the sinuses. Mucosal secretions become trapped, local defenses are impaired, and bacteria from adjacent surfaces begin to proliferate

CLINICAL PRESENTATION • General

• There are three clinical presentations that are most consistent with acute bacterial versus viral rhinosinusitis:

1. Onset with persistent signs or symptoms compatible with acute rhinosinusitis, lasting for ≥10 days without any evidence of clinical improvement

2. Onset with severe signs or symptoms of high fever (≥39°C [102.2°F]) and purulent nasal discharge or facial pain lasting for at least 3 to 4 consecutive days at the beginning of illness

3. Onset with worsening signs or symptoms characterized by new-onset fever, headache, or increase in nasal discharge following a typical viral URI that lasted 5 to 6 days and were initially improving (“double sickening”)

• Signs and Symptoms

• Purulent anterior nasal discharge, purulent or discolored posterior nasal discharge, nasal congestion or obstruction, facial congestion or fullness, facial pain or pressure, fever, headache, ear pain/pressure/fullness, halitosis, dental pain, cough, and fatigue

Diagnosis

• The greatest barrier to efficient use of antibiotics in acute bacterial rhinosinusitis is the lack of a simple and accurate diagnostic test.

• The gold standard for diagnosis is sinus puncture with recovery of bacteria in high density (104 colony-forming units/mL [107 cfu/L] or greater)15; however, sinus puncture is invasive and costly, and can be painful, so it is not routinely done.

• Sinus radiography can help, but it is not routinely recommended.

• Because there is no simple and accurate office-based test for acute bacterial rhinosinusitis, clinicians rely on clinical findings to make the diagnosis

Pharmacological Treatment

• The first step is to differentiate viral and bacterial rhinosinusitis

• The Infectious Diseases Society of America (IDSA): amoxicillin/clavulanateas first-line treatment, without watchful waiting.

• The American Academy of Otolaryngology—Head and Neck Surgery Foundation (AAO-HNSF) guideline: watchful waiting, without antibiotics, unless symptoms fail to improve within 7 days then amoxicillin as first-line treatment.

An

tibio

tics

and

Do

ses

for

Acu

te B

acte

rial

Rh

ino

sin

usi

tis

in

Chil

dre

n

Anti

bio

tics

and D

ose

s fo

r A

cute

Bac

teri

al

Rhin

osi

nusi

tis

in A

dult

s

• High-dose amoxicillin-clavulanate is recommended as second line for initial empirical therapy in children and adults. Doxycycline is also second line for adults but should be avoided in children.

• High-dose amoxicillin-clavulanate is preferred in the following situations:

1. geographic regions with high endemic rates (10% or greater) of invasive penicillin-nonsusceptible S. pneumoniae,

2. severe infection,

3. attendance at daycare,

4. age less than 2 or greater than 65 years,

5. recent hospitalization,

6. Antibiotic use within the last month, and

7. immunocompromised persons

• Due to resistance;

1. Cephalosporins, are no longer recommended as monotherapy

2. Macrolides are no longer recommended

3. Trimethoprim-sulfamethoxazole has not been recommended for some time

• Duration of treatment: 10-14 days in children with uncomplicated disesse and 5-7 days in adults

Non-Pharmacological Treatment

• Several nonprescription therapies are used in the management of nonbacterial rhinosinusitis for symptomatic relief.

• These include:

1. Nasal decongestant sprays that reduce inflammation by vasoconstriction. Use should be limited to no more than 3 days to prevent the development of tolerance and/or rebound congestion.

2. Oral decongestants may also aid in nasal/sinus patency.

3. Irrigation of the nasal cavity with saline and steam inhalation may be used to increase mucosal moisture, and

4. Mucolytics (eg, guaifenesin) may be used to decrease the viscosity of nasal secretions

• If a patient is suspected of having acute bacterial rhinosinusitis, then decongestants and antihistamines are not recommended. These can dry mucosa and disturb clearance of mucosal secretions.

• Intranasal saline irrigation with either physiologic or hypertonic saline is recommended for adults.

• Intranasal corticosteroids are recommended only for patients with a history of allergic rhinitis.

Non-Pharmacological Treatment

ACUTE PHARYNGITIS • Pharyngitis is an acute infection of the oropharynx or nasopharynx

• Although viral causes are most common, group A β-hemolytic Streptococcus (GABHS, also known as S. pyogenes) is the primary bacterial cause; pharyngitis due to GABHS is commonly known as “strep throat.

• Suppurative and nonsuppurative complications include acute rheumatic fever, acute glomerulonephritis, reactive arthritis, peritonsillar abscess, retropharyngeal abscess, cervical lymphadenitis, mastoiditis, otitis media, rhinosinusitis, and necrotizing fasciitis.

• Seasonal outbreaks occur, and the incidence of GABHS is highest in winter and early spring.

• The incubation period is 2 to 5 days, Untreated, patients with streptococcal pharyngitis are infectious during the acute illness and for another week thereafter. Effective antibiotic therapy reduces the infectious period to about 24 hours

Pathophysiology

• The mechanism by which GABHS causes pharyngitis is not well defined.

• Asymptomatic pharyngeal carriers of the organism may have an alteration in host immunity (eg, a breach in the pharyngeal mucosa) and the bacteria of the oropharynx may migrate to cause an infection.

• Pathogenic factors associated with the organism itself, pyrogenic toxins, hemolysins, streptokinase, and proteinase, may also play a role.

CLINICAL PRESENTATION

• General

• A sore throat of sudden onset that is mostly self-limited

• Fever and constitutional symptoms resolving in about 3 to 5 days

• Clinical signs and symptoms are similar for viral causes and nonstreptococcal bacterial causes

• Signs and Symptoms of GABHS Pharyngitis

• Sore throat

• Pain on swallowing

• Fever

• Headache, nausea, vomiting, and abdominal pain (especially in children)

• Erythema/inflammation of the tonsils and pharynx with or without patchy exudates

• Enlarged, tender lymph nodes

• Red swollen uvula, petechiae on the soft palate, and a scarlatiniform rash

• Laboratory Tests

• Throat swab and culture

• Rapid antigen-detection test (RADT)

Treatment • The goals of treatment for pharyngitis are to improve clinical

signs and symptoms, minimize adverse drug reactions, prevent transmission to close contacts, and prevent acute rheumatic fever and suppurative complications

• Antibiotic overuse has been well documented. Antibiotics are prescribed for 60% of patients who visit their provider with a complaint of “sore throat.” This rate is well above the incidence of GABHS pharyngitis

• Antibiotic therapy should be reserved for those patients with clinical and epidemiologic features of GABHS pharyngitis, preferably with a positive laboratory test.

• Empirical therapy is not recommended; however, if used while results are pending, it is important to discontinue empirical antibiotics once laboratory results come back as negative

Nonpharmacologic Therapy

• Supportive care should be offered to all patients with acute pharyngitis

• Pharmacologic supportive care interventions include antipyretic medications, analgesics, and nonprescription lozenges and sprays containing menthol and topical anesthetics for temporary relief of pain.

• There are limited data for use of corticosteroids to reduce the symptoms of GABHS pharyngitis, and given the risk of adverse effects, their use is not recommended.

• Because pain is often the primary reason for visiting a physician, emphasis on analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs to aid in pain relief is strongly recommended.

Antibiotics and Doses for Group A β-Hemolytic

Streptococcal Pharyngitis

Pharmacological Treatment

• Because penicillin and amoxicillin have a narrow spectrum of activity and are readily available, safe, and inexpensive, they are considered to be the treatments of choice.

• Amoxicillin may be preferable for children with GABHS pharyngitis because the suspension is more palatable than penicillin. Gastrointestinal (GI) adverse effects and rash are more common with amoxicillin.

• A once-daily, extended-release formulation of amoxicillin has been approved for treatment of GABHS pharyngitis in adults and children aged 12 years and older

Pharmacological Treatment

• In penicillin-allergic patients, azithromycin, clarithromycin, clindamycin, or a first-generation cephalosporin such as cephalexin can be used if the reaction is nonimmunoglobulin E (IgE)–mediated

• GABHS resistance rates to tetracyclines are high. Sulfonamides and trimethoprim-sulfamethoxazole have poor eradication rates for GABHS; therefore, use of these antibiotics is no longer recommended

• The newer fluoroquinolones have activity against GABHS, but are expensive and have a broad spectrum of activity

• The duration of therapy for GABHS pharyngitis is 10 days, except for benzathine penicillin and azithromycin, to maximize bacterial eradication

• Patients with documented histories of rheumatic fever (including cases manifested solely by Sydenham’s chorea) and those with definite evidence of rheumatic heart disease should receive continuous antibiotic prophylaxis initiated as soon as the patient is diagnosed and the initial infection has been treated.

• The duration of secondary prophylaxis is individualized based on patient risk of recurrence of rheumatic fever and/or rheumatic heart disease.

• Intramuscular benzathine penicillin G every 4 weeks is the recommended regimen for secondary prevention in the United States in most circumstances

• Additional options for secondary prophylaxis include oral penicillin V and sulfadiazine (penicillin-allergy).

Pharmacological Treatment

Evaluation of Therapeutic Outcomes

• Most pharyngitis cases are self-limited; however, antibiotics hasten resolution when given early for proven cases of GABHS pharyngitis.

• Generally, fever and other symptoms resolve within 3 to 4 days of onset without antibiotics; however, symptoms will improve 0.5 to 2.5 days earlier with antibiotic therapy.

• Follow-up testing is generally not necessary for index cases or asymptomatic contacts; however, throat cultures 2 to 7 days after completion of antibiotics are warranted for patients who remain symptomatic or when symptoms recur despite completion of treatment

Thank you

36