Therapeutics 2 course

1. Therapeutics 2 course N.B Upper respiratory tract infection

2. Introduction • The respiratory tract is divided into upper and lower parts: • The upper respiratory tract : sinuses, middle ear, pharynx….. • The lower respiratory tract: bronchi, bronchioles and alveoli. • Otitis media, rhinosinusitis, and pharyngitis are the three most common upper respiratory tract infections. • Most URIs are caused by viruses, have nonspecific symptoms, and resolve spontaneously. Antibiotics are not effective for viral URIs, and their excessive use has contributed to resistance N.B

3. OTITIS MEDIA • Is an inflammation of the middle ear. • Acute otitis media (AOM)is the most common reason for antimicrobial use in children, and is associated with expenditures of almost $3 billion annually. • Acute otitis media is most common from the ages of 3 months to 3 years, although the highest incidence occurs between 6 and 2 years of age. • By 3 years of age, more than 80% of children have at least one episode, and up to 65% have recurrent infections by 5 years of age. • Most children will have had at least one episode by the time they reach 1 year of age N.B

4. Incidence is higher in the winter months, concurrent with viral upper respiratory illnesses. • Several risk factors for AOM have been identified and include: N.B

5. There are three subtypes of otitis media: • acute otitis media • otitis media with effusion • chronic otitis media. • The three are differentiated by • acute signs of infection • evidence of middle ear inflammation • presence of fluid in the middle ear N.B

6. Etiology • Approximately 40% to 75% of acute otitis media cases are caused by viral pathogens. Although AOM occurs frequently with viral URIs, bacteria are isolated from middle ear fluid in up to 90% of children with AOM • Common bacterial pathogens include Streptococcus pneumoniae (35% to 40%), Haemophilus influenzae (30% to 35%), and Moraxella catarrhalis (15% to 18%). • Antibiotic resistance heavily influences the treatment options for AOM. Penicillin-resistant S. pneumoniae (PRSP) exhibit intermediate resistance N.B

7. PRSP are frequently resistant to other drug classes, including sulfonamides, macrolides, and clindamycin, but are usually susceptible to levofloxacin. • Risk factors have been identified for amoxicillin-resistant bacteria(Amoxicillin resistance is less common). These include attendance at child care centers, recent receipt of antibiotic treatment (within the past 30 days), and age younger than 2 years. N.B

8. Pathophysiology • The middle ear is the space behind the tympanic membrane, or eardrum. A noninfected ear has a thin, clear tympanic membrane. • In otitis media, this space becomes blocked with fluid, resulting in a bulging and erythematous tympanic membrane. The bacteria proliferate and cause infection. • Children tend to be more susceptible to otitis media than adults because the anatomy of their Eustachian tube is shorter and more horizontal, facilitating bacterial entry into the middle ear. N.B

9. Viscous effusions caused by allergy or irritant exposure contribute to impaired mucociliary clearance and AOM in susceptible individuals. Effusions can persist for up to 6 months after an episode of AOM. • Atopic children experience chronic OME that may require tympanostomy tube placement to reduce complications such as hearing and speech impairment and recurrent AOM. • Viral URIs impair eustachian tube function and cause mucosal inflammation, impairing mucociliary clearance and promoting bacterial proliferation and infection. N.B

10. Clinical Presentation • an acute onset of otalgia (ear pain). • For parents of young children, irritability and tugging on the ear are often the first clues that a child has acute otitis media. • A diagnosis of acute otitis media requires the following three criteria: • acute signs of infection • evidence of middle ear inflammation • presence of fluid in the middle ear. N.B

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13. General Approach to Treatment • The first step is to differentiate acute otitis media from otitis media with effusion or chronic otitis media. • The therapeutic strategy should be changed if complications develop or if symptoms fail to resolve within 3 days. • Nonpharmacologic Therapy: • Children with recurrent AOM or chronic OME with impaired hearing or speech may benefit from surgery (tympanostomytube placement) N.B

14. Pharmacological therapy: • Acetaminophen or a nonsteroidal antiinflammatory drug, such as ibuprofen, should be offered early to relieve pain in acute otitis media….depend on age • Eardrops with a local anesthetic, such as amethocaine, benzocaine, or lidocaine, provide pain relief when administered with oral pain medication to children aged 3 to 18 years • Because of minimal benefit and increased side effects, neither decongestants nor antihistamines should be routinely recommended in cases of acute otitis media or otitis media with effusion N.B

15. Antibiotics N.B

16. Antibiotics • Severe illness consists of otalgia, irritability, fussiness, lethargy, less interest in eating, and a temperature of at least 39◦C. • Generally, infants 6 months of age and younger should receive antibiotic therapy in all cases. • Infants and children 6 months to 2 years of age can be managed with observation for 48 to 72 hours in the case of an uncertain diagnosis and if illness is not severe. • Children 2 years of age and older can be managed with observation even in the case of a certain diagnosis, although illness should be non severe N.B

17. If antibiotics are to be administered, then amoxicillin should be given to most children (80 to 90 mg/kg/day in two divided doses). • High-dose amoxicillin (80–90 mg/ kg/day) is preferred over conventional doses (40–45 mg/kg/day) because higher middle ear fluid concentrations can overcome pneumococcal penicillin resistance without substantially increasing adverse effects. • If pathogens that produce β-lactamase are known or suspected, then amoxicillin should be given in combination with a β-lactamase inhibitor: amoxicillin–clavulanate (90 mg/kg/day of amoxicillin with 6.4 mg/kg/day of clavulanate in two divided doses). N.B

18. In patients with moderate to severe illness (temperature greater than 39°C [102°F] and/or severe otalgia), amoxicillin– clavulanate is recommended N.B

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21. Use of trimethoprim–sulfamethoxazole and erythromycin–sulfisoxazole is discouraged because of high rates of resistance. • Intramuscular ceftriaxone is the only antibiotic other than amoxicillin that achieves middle ear fluid concentrations above the MIC for greater than 40% of the dosing interval. • Ceftriaxone should be reserved for severe and unresponsive infections or for patients for whom oral medication is inappropriate because of vomiting, diarrhea, or possible nonadherence N.B

22. Patients with a penicillin allergy can be treated with several alternative antibiotics. If the reaction is not type I hypersensitivity, cefdinir, cefpodoxime, or cefuroxime can be used. If the reaction is type I, a macrolide such as azithromycin or clarithromycin may be used. • Traditional recommendations call for 10 days of antibiotic therapy; however, some experts have speculated that patients can be treated for as little as 3 to 5 days. • Short-course treatment is not recommended in children younger than 2 years of age. N.B

23. In children at least 6 years old who have mild to moderate acute otitis media, a 5- to 7-day course may be used. • Recurrent acute otitis media is defined as at least three episodes in 6 months or at least four episodes in 12 months. • Recurrent infections are of concern because patients younger than 3 years are at high risk for hearing loss and language and learning disabilities. N.B

24. Treatment can be delayed until the onset of symptoms of an upper respiratory tract infection or antibiotic prophylaxis can be limited to 6 months’ duration during the winter months. • Surgical insertion of tympanostomy tubes (T tubes) is an effective method for the prevention of recurrent otitis media. These small tubes are placed through the inferior portion of the tympanic membrane under general anesthesia and aerate the middle ear. Children with recurrent acute otitis media should be considered for T-tube placement. N.B

25. Prevention • Vaccinations may prevent AOM in certain patients. Influenza vaccine is more effective in children older than 2 years because of impaired immune responses and immature host defenses in infants and toddlers. • Antibiotic prophylaxis is not recommended because of antibiotic resistance trends. • Exclusive breast-feeding for the first 6 months of life and avoidance of tobacco smoke are advised, but the effects of these interventions remain unproven. N.B

26. Acute otitis media: Update 2015 N.B

27. Case example 1 • A 13-month-old boy presents to the pediatric clinic with 2 days of fever (maximum temperature of 39.3°C [102.7°F]), rhinorrhea, and fussiness. His mother reports that he was rubbing his left ear throughout the day yesterday. She states that he is irritable and he was crying intermittently throughout the night last night. He has not eaten much today. He attends daycare 3 days a week and has a 5-year-old sister who recently had a cold. • Meds: Acetaminophen drops 120 mg orally every 4 to 6 hours as needed for fever • ROS: (+) rhinorrhea and fever, (–) vomiting, diarrhea, or cough N.B

28. PE: • Gen: Irritable child but consolable • VS: BP 100/64 mm Hg, P 130 beats/min, RR 22 breaths/min, • T 39.1°C (102.4°F) • HEENT: Erythema and severe bulging of the left tympanic membrane with the presence of middle ear fluid; the right tympanic membrane is obscured with cerumen. • Patient has type 1 allergy to penicillin • What information is suggestive of acute otitis media (AOM)? • What risk factors does this child have for AOM? • Given this information, what nonpharmacologic and pharmacologic therapy do you recommend? N.B

29. Case example 2 • C.D. is a 7-month-old, 8-kg infant , stays in day care, who during the last 2 days has developed cough and rhinorrhea, became irritable and at times inconsolable, and now has a temperature of 102.4◦F (39.1◦C). Physical examination shows bulging, dark, yellow opaque tympanic membranes bilaterally. This is the first time he has had these symptoms • What signs and symptoms does C.D. exhibit that are consistent with acute otitis media • How should AOM be diagnosed? • What are the risk factors for AOM in the case? • What is the appropriate treatment for the case? N.B

30. Acute Pharyngitis • Pharyngitis is an acute infection of the oropharynx or nasopharynx. • viral causes are most common… rhinovirus • group A β-hemolytic streptococci (GABHS; also known as S. pyogenes), is the primary bacterial cause. • Complications include acute rheumatic fever, acute glomerulonephritis, reactive arthritis, peritonsillar abscess, retropharyngeal abscess, cervical lymphadenitis, mastoiditis, otitis media, rhinosinusitis N.B

31. Children 5 to 15 years of age are most susceptible • Pharyngitis in a child younger than 3 years of age is rarely caused by GABHS. • Seasonal outbreaks occur, and the incidence of GABHS is highest in winter and early spring. The incubation period is 2 to 5 days. N.B

32. Pathophysiology • Asymptomatic pharyngeal carriers of the organism may have an alteration in host immunity (e.g., 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 may also play a role. These include pyrogenic toxins, hemolysins,streptokinase, and proteinase. N.B Clinical Presentation • Sore throat ( pain) is the most common symptom of pharyngitis • Laboratory tests should not be performed unless the patient has symptoms consistent with GABHS pharyngitis.

33. 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 N.B

34. Signs Suggestive of Viral Origin for Pharyngitis • • Conjunctivitis • • Coryza • • Cough Nonpharmacologic Therapy: • antipyretic medications, analgesics( NSAIDs, acetaminophen) • nonprescription lozenges • sprays containing menthol and topical anesthetics for temporary relief of pain • use of corticosteroids …..is not recommended N.B

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36. Amoxicillin suspension is more palatable than penicillin and has the advantage of a once-daily dosing regimen. • In patients with a type I hypersensitivity to penicillins, azithromycin, clarithromycin, or clindamycin may be used. In those with a non–type I allergy to penicillin, a first-generation cephalosporin may be considered. • Newer macrolides such as azithromycin and clarithromycin are equally effective as erythromycin and cause fewer GI adverse effects. N.B

37. GABHS resistance rates to tetracyclines are high. Sulfonamides and trimethoprim– sulfamethoxazole have poor eradication rates for GABHS. • The newer fluoroquinolones have activity against GABHS but are expensive and have a broad spectrum of activity. • The impact of appropriate antibiotic therapy is limited to decreasing the duration of signs and symptoms by 1 or 2 days. • The duration of therapy for GABHS pharyngitis is 10 days…except for azithromycin N.B

38. Cephalosporins may be more effective than penicillin for relapse prevention and nasopharyngeal eradication, particularly in asymptomatic carriers. • Usual duration of therapy is 10 days, but 5-day courses of some cephalosporins are as effective for streptococcal eradication as 10 days of penicillin N.B

39. Case example • P.J., a 6-year-old boy weighing 23.4 kg, presents to the pediatrician’s office complaining of fever, sore throat, and headache. His mother reports that he initially complained of sore throat about 12 hours ago. His temperature this morning was 102◦F. He has had no other symptoms. He takes no medications and has no known drug allergies. Physical examination reveals erythematous tonsils and throat, as well as an enlarged anterior cervical lymph node. • Are P.J.’s symptoms more consistent with GAS or viral pharyngitis? • What is the appropriate treatment for this case? N.B

40. ACUTE BACTERIAL RHINOSINUSITIS • Sinusitis is an inflammation and/or infection of the paranasal sinuses, or membrane-lined air spaces, around the nose. • The term rhinosinusitis is now preferred because sinusitis typically also involves the nasal mucosa. • Majority of rhinosinusitis infections are viral • One in five antibiotics prescribed for adults in the United States is for rhinosinusitis • Acute rhinosinusitis is characterized by symptoms that persist for up to 4 weeks, whereas chronic rhinosinusitislasts for more than 12 weeks. N.B

41. Etiology • Acute bacterial rhinosinusitis is caused, most often, by the same bacteria implicated in acute otitis media: S. pneumoniae and H. influenzae. • These organisms are responsible for ~50% to 70% of bacterial causes of acute bacterial rhinosinusitis in both adults and children. N.B

42. 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 • Dental pain, cough, and fatigue • Children: Persistent nasal or postnasal drainage, nasal congestion, mouth breathing, persistent cough (particularly at night), morning periorbital edema or facial swelling, fatigue, facial or tooth pain N.B

43. Onset with persistent signs or symptoms compatible with acute rhinosinusitis, lasting for ≥10 days without any evidence of clinical improvement. • Onset with severe signs or symptoms of high fever (≥39°C [102°F]) and purulent nasal discharge or facial pain lasting for at least 3 to 4 consecutive days at the beginning of illness • 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 N.B

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45. General Approach to Treatment • The first step is to delineate viral and bacterial rhinosinusitis • Viral rhinosinusitis typically improves in 7 to 10 days; therefore, a diagnosis of acute bacterial rhinosinusitis requires persistent symptoms (10 days or greater) or a worsening of symptoms after 5 to 6 days. • Potential reasons for referral include mental status changes, visual disturbances, immunosuppressive illness, nosocomial infections, anatomic defects causing obstruction and possibly requiring surgery, unusually severe symptoms, multiple recurrent episodes (3 to 4/y), unilateral findings, risk factors for unusual or resistant pathogens, and history of antibiotic failure. N.B

46. pharmacologic Therapy • nasal decongestant sprays that reduce inflammation by vasoconstriction, such as phenylephrine and oxymetazoline. • Use should be limited to no more than 3 days to prevent the development of tolerance and/or rebound congestion. • Oral decongestants also may aid in nasal/sinus patency. • Irrigation of the nasal cavity with saline and steam inhalation may be used to increase mucosal moisture N.B

47. mucolytics (e.g., 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 corticosteroids are now recommended for patients with a history of allergic rhinitis N.B

48. Moderate infection N.B

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50. cephalosporins are no longer recommended as monotherapy due to variable rates of resistance against S. pneumoniae. • Macrolides are no longer recommended because of high rates of S. pneumoniae resistance • Trimethoprim–sulfamethoxazole has not been recommended for some time due to resistance among S. pneumoniae and H. influenzae. • For adults, the recommended duration is only 5 to 7 days N.B