Rosalie Sagraves, PharmD, FCCP
Spring 1998
Rosalie Sagraves, PharmD, FCCP
Spring 1998
Pediatric
Infectious Diseases I
Otitis Media
I. Clinical Classification of Otitis Media1-5
II.
Anatomy and Physiology3
III.
Epidemiology4-6
IV. Clinical Presentation and Diagnosis
V. Etiology
VI. Treatment of Acute Otitis Media
VII. Treatment of Various Other Types of OM
Goal: The student should familiarize himself/herself with the pharmacotherapy of otitis media in pediatric patients.
Learning Objectives:
The student should be able to:
1. Recognize the risk factors for otitis media (OM);
2. Differentiate between various types of OM and understand terminology used to describe those types;
3. Discuss the rationale for treating acute OM (AOM) and the occurrence of spontaneous remission;
4. Recommend an appropriate treatment plan for AOM considering cost-effectiveness and compliance issues; and
5. Recognize the place in therapy for the use of antibiotic prophylaxis, vaccinations, corticosteriods, and antihistamines/decongestants.
Required Reading:
Richer M, LeBel M. Upper Respiratory Tract Infections. In: Pharmacotherapy, A Pathophysiologic Approach. 3rd edition. DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM (eds.). Elsevier Science Publishing, NY 1997; 2017-36.
Suggested Readings:
1. Thoene DE, Johnson CE. Pharmacotherapy of Otitis Media. Pharmacotherapy 1991;11: 212.
2. Drugs for treatment of acute otitis media in children. Medical Letter. March 4, 1994;36: 19.
3. Sagraves R, Maish W, Kameshka A. Update on otitis media. Part 1. Epidemiology and pathophysiology. Am Pharm 1992;12:27.
4. Sagraves R, Maish W, Kameshka A. Update on otitis media. Part 2. Treatment. Am Pharm 1993;33:29.
5. Ruuskanen O, Heikkinen T. Otitis media: etiology and diagnosis. Pediatr Infect Dis J 1994;13:S23.
6. Pichichero M. Assessing the treatment alternatives for acute otitis media. Pediatr Infect Dis J 1994;13:S27.
Glossary of Terms (terms that are needed to understand otitis media):
Auditory ossicles - malleus, incus, and stapes are the three small bones found in the middle ear that connect the tympanic membrane (TM) with the oval window of the cochlea. These create the "landmarks" observed on the otoscopic examination.
Effusion - collection of fluid in the middle ear behind the TM.
Eustachian tube (ET) - part of the middle ear which connects the ear to the nasopharynx.
Light reflex - cone of light or reflection of light off the TM when the light from the otoscope is directed into the ear.
Myringotomy - incision made in the TM.
Otitis media - inflammation of the middle ear.
Otorrhea - discharge through a perforated TM.
Otoscope - an instrument containing a light source that can be used to visualize the auditory canal, TM, and the auditory ossicles.
Pneumatic otoscope - an otoscope that can be used to "exert pressure" on the TM to test the mobility of that membrane.
Tinnitis - ringing or buzzing in the ears.
Tympanic membrane (TM) - eardrum; separates the external ear canal from the middle ear and can convert sound into vibrations.
Tympanometry - method of determining middle function and detecting middle-ear effusion (fluid). Measures sound returned from the tympanic membrane under pressure to determine if a middle ear effusion is present.
Tympanostomy tubes - small vinyl or plastic tubes inserted through a myringotomy to permit air (and not water) to pass into the middle ear.
Outline
I. Clinical Classification of Otitis Media1-5
(This classification is used to emphasize that there is not just one type of otitis media)
A. Otitis Media without Effusion (OME; myringitis)
1. Presence of erythema without fluid collection; TM mobility is normal
2. Seen in the early stages of acute otitis media (AOM) or as OM resolves
B. Acute Otitis Media (AOM; acute suppurative OM or purulent OM)
1. A rapid onset of signs and symptoms associated with middle ear inflammation and at least one of the following: pulling on the ear lobe (otalgia), ear pain, fever or irritability.
2. TM is noted to be bulging, opaque and has decreased mobility. The TM may or may not be erythematis. Otorrhea may be present if the TM ruptures or a myringotomy is performed.
C. Otitis Media with Effusion (OME)
1. Distinguished from AOM in that signs and symptoms of an acute infection are not present, but hearing loss can occur.
2. Stages based on duration of the effusion:
a. Acute: < 3 weeks
b. Subacute: > 3 weeks
c. Chronic: > 8 weeks
(Please see figure 101.1 in your required reading for an appreciation of the anatomic differences between an infant's and a adult's ear)
A. Function of the Eustachian Tube (ET)
1. The ET helps with the ventilation of the middle ear; helps maintain equilibrium of pressure between middle ear with atmospheric pressure.
2. The ET also functions in the clearance of secretions from the middle ear.
3. In addition, the ET helps to protect the middle ear from sound, pressure and the build up of secretions.
B. Normal Eustachian Tube
1. Normally the ET is functionally obstructed or collapsed at rest.
2. Usually there is a slight negative pressure in the middle ear.
3. During swallowing, the ET intermittently opens; and this helps in maintaining pressure in the middle ear.
C. Pathogenesis of Otitis Media3
1. ET Dysfunction
a. Functional obstruction of the ET may be associated with the following:
1.) Persistent collapse of ET
2.) Craniofacial differences in children versus those noted in adults
3.) Differences in length and position of ET in children versus adults (e.g., in children, the ET is shorter and more horizontal than in adults)
4.) Less cartilage support around the ET in children (i.e., floppy ET in children)
b. Functional obstruction may result in the following:
1.) Persistently high negative middle ear pressure
2.) Atelectasis resulting in sterile otitis media with effusion
3.) Aspiration of nasopharyngeal secretions which may result in an acute bacterial otitis media with effusion
c. Mechanical obstruction
1.) Inflammation and swelling may occur in association with an upper respiratory infection, allergy, etc.
2.) Compression of ET may occur with enlarged adenoids or less commonly by the presence of a tumor
2. Abnormal patency of the ET
a. Air readily flows from nasopharynx into middle ear for ventilation, but it may also allow nasopharyngeal secretions to reflux into the middle ear.
b. Low tubal resistance may increase the risk of OM
3. Allergy may result in the following:
a. Inflammatory swelling of the ET
b. Aspiration or reflux of nasopharyngeal secretions into the middle ear
A. Incidence by Age
1. OM is the most common pediatric infectious disease.
2. Approximately 10% of children will have one episode of OM by age 3 months; 60% by age one year; 70% by age 3 years (figures vary with studies); a plateau of 4 - 5% is reported during elementary school.
3. By age 7 years of age, 93% of children will have had otitis media and 40% will have had more than 3 episodes.
4. Peak incidence - 9 - 12 months of age
B. Incidence by Gender: Incidence in males is greater than in females in most studies.
C. Incidence by Racial Groups
1. Native Americans and Hispanics > Caucasians > African-Americans
2. Differences in incidence may be related to socioeconomic, sociocultural or other factors
D. Host Factors
1. There may be structural abnormalities such as cleft palate that can increase the risk for otitis. Children with Down syndrome are at an increased risk based on facial anatomic differences.
2. Presence of allergies
3. Feeding method . Bottle-feeding is associated with an increased incidence of otitis. This may also be related to the position used during infant feeding. Infants who are breast-fed may receive secretory IgA or prostaglandin E1 in breast milk.
4. The immaturity of the immune system or immunodeficiency problems (e.g., HIV) may place an infant or child at increased risk for OM.
E. Environmental Factors
1. Children who are carried for in day-care centers are at an increased risk for AOM, recurrent episodes and even OME.
2. Secondhand smoke has been shown to increase a child's risk for developing otitis.
F. Season
1. Higher incidence in the winter months when viral infections are more common.
2. Incidence may parallel outbreaks of viral infections especially those caused by influenza A or B, respiratory syncytial virus, adenovirus or rhinovirus.
IV. Clinical Presentation and Diagnosis
A. History
B. Presence of clinical signs and symptoms of AOM:
• Ear lobe pulling • Irritability or restlessness • Earache (otalgia) • Nonspecific symptoms, e.g., diarrhea and vomiting • Fever • Feeding problems • Rhinitis and cough • Hearing impairment
C. OM with effusion (chronic):
• May note hearing loss
• TMs on examination may appear normal but motility is decreased
D. Otoscopic examination
Table I lists differences in TM color, translucency and compliance between normal TMs and TMs in infants/children with acute otitis media.
Table I - Otoscopic Examination
TM Color - Normal: +/- red or pearly gray - Abnormal: red, blue, or yellow TM Translucency - Normal: ground glass - Abnormal: opaque TM Compliance - Normal: mobile - Abnormal: bulging, impaired mobility
E. Tympanometry. In addition to visually observing the TM via otoscopic examination, a tympanometer can be used which can be used to determine middle ear function and detect middle ear effusion (fluid). Sound is measured as it is returned from the TM under pressure to determine if a middle ear effusion is present.
F. Tympanocentesis may be indicated for seriously ill patients who need middle ear fluid cultured, children with scarred TMs, children who do not respond to appropriate therapy, neonates with OM, and immunocompromised patients
G. Audiograms are printouts of the sound waves produced by the movement of the TM.
Table II. Common Organisms Associated with Otitis Media (References 1 - 3)
Microorganisms (Listed as %)
Acute OM Chronic OM with effusion
Chronic Suppurative OM Neonatal OM with effusion Streptococcus pneumoniae 26 - 50 8 4 18 - 20 H. influenzae (noncapsulated) H. influenzae type b
14 - 31 2 - 10
13 3 12 - 15 Moraxella catarrhalis 0 - 30 9 3 5 Streptococcus pyogenes Grp. A ß Hemolytic Strep.
0 - 24 1 6 3 Staphylococcus aureus 0 - 3 3 15 - 27 8 Staphylococcus epidermis 1 - 2 19 - 37 9 - 11 Pseudomonas aeruginosa 0 - 2 4 50 - 88 2 Enteric organisms 0 - 4 8 - 10 12 -20 Anaerobic organisms --- --- 54 --- Sterile 25 - 35 34 - 45 32
VI. Treatment of Acute Otitis Media
A. Treatment controversy
1. There is no universal accepted method for the treatment of otitis although in the U.S., antibiotics are the mainstay of the treatment for AOM.
2. Resolution of AOM may occur spontaneously in 14 - 86% of patients without antimicrobial therapy.
3. Alternatives to antimicrobial therapy include:
a. Antihistamines/decongestants have been used for persistent OME, but efficacy has not been proven.
b. Corticosteriods - studies have shown mixed results and frequent relapses.
c. Duration of therapy is currently 10 - 14 days, but various studies have shown shorter courses may be adequate.
B. Why Empirical Antimicrobial Therapy?
1. Complications and sequelae can occur secondary to AOM.
2. Antimicrobial therapy has reduced the incidence and severity of complications and sequelae.
a. Extracranial - occur frequently and include hearing loss, TM perforation, chronic suppurative OM, etc.
b. Intracranial - rarely occur but can include meningitis, brain abscesses, etc.
C. Antibiotic Therapy
1. Selection of antibiotic therapy should be based on susceptibility of organisms, penetration into the middle ear, efficacy, compliance, dosage form availability, adverse effects and cost.
Table III. Antibiotic Selection for Acute Otitis Media Based on Organism (Reference 3)
Antibiotic Strep. pneumo. H. influenzae ß lact. - ß lact. +
M. catarrhalis ß lact. - ß lact. +
Grp A Strep.
Staph. aureus
Amoxicillin or ampicillin + + - + - + +/- Amoxicillin-clavulanate + + + + + + + Erythromycin-sulfisoxazole +/- +/- +/- +/- +/- +/- +/- Trimethoprim-sulfamethoxazole +/- +/- +/- + + - + Cefaclor + + +/- + +/- + +/- Cefuroxime axetil + + + + + + + Cefpodoxime proxetil + + + + + + +/- Cefprozil + + + + + + + Loracarbef + + + + + + + Cefixime +/- + + + + + - Clarithromycin + + + + + + +
(Note: the information provided is based on available data; and "+", "-", "+/-" reflects in vitro activity, inactivity, and variable activity)
2. Penetration into middle ear fluid: Please see Table 101.3 in your required reading and accompanying information for an overview of antimicrobial penetration.
3. Compliance - consider how often medication must be given; most patients become asymptomatic within 24-48 hrs after starting therapy that may contribute to noncompliance with duration of therapy.
4. Dosage forms available and palatability (see Table IV)
5. Adverse effects (see Table IV)
6. Cost considerations should take into consideration:
a. Drug acquisition cost
b. Efficacy of drug
c. Time lost from work because of physician appointments
d. Physician office visits
Table IV. Antimicrobial Product Information (Reference 3)
Drug Product Daily Dosage Common Adverse Effects Dosage Forms Strength (mg or mg/5 mL) Cost* Amoxicillin 40 mg/kg ÷ Q8H Loose stools/diarrhea (4-11%), maculopap- ular rash (1-10%) Capsules Chew tablets
Drops
Suspension
250, 500 125, 250
250
125, 250
6.02 Amoxicillin-clavulanate (Augmentin™)
40 mg/kg as amoxicillin ÷ Q8H Loose stools & diarrhea (13-24%), maculopapular rash (1-10%), vomiting
Tablets Chew tablets
Suspension
250, 500 of amoxicillin
125, 250 of
amoxicillin
125, 250 of amoxicillin
48.10 Erythromycin-sulfisoxazole 50 mg/kg of erythromycin ÷ Q6H Cramps, flatulence & diarrhea (4-25%), rash (5%) Suspension 200 erythromycin 22.77 (generic)
Trimethoprim-sulfamethoxazole 8 mg/kg of trimethoprim ÷ Q12H Loose stools & diarrhea (8-10%), rash (5%), blood dyscrasia Tablets Suspension
80, 160 of trimethoprim 40 of trimethoprim
12.26 (Septra™)
Cefaclor (Ceclor™)
40 mg/kg ÷ Q8-12H Loose stools & diarrhea (1.4-15%), maculopapular rash (5%), serum sickness (1-2%) Capsules Suspension
250, 500 125, 187, 250, 375
51.78 Cefuroxime axetil (Ceftin™)
< 2 y/o 250 mg > 2 y/o 500 mg ÷ Q12H
Nausea & vomiting (bitter taste), and diarrhea (4%) Tablets Suspension
125, 250, 500 125
62.84 Cefpodoxime proxetil (Vantin™) 10 mg/kg ÷ Q12H Diarrhea or loose stools (1.9-7%), bitter taste (1.4%) Tablets Suspension
100, 200 50, 100
43.50 Cefprozil (Cefzil™)
30 mg/kg ÷ Q12H Diarrhea (2.9%), rash (<1%) Tablets Suspension
250, 500 125, 250
45.59 Loracarbef (Lorbid™)
30 mg/kg ÷ Q12H Diarrhea (5.8%), nausea (3.5%), rash (2.9%), rhinitis Tablets Suspension
200, 400 100
56.40 Cefixime (Suprax™)
8 mg/kg ÷ Q12H or Q24H Loose stools & diarrhea (14-30%), maculopapular rash (0.4%) Tablets Suspension
200, 400 100
45.66 Clarithromycin (Biaxin™)
15 mg/kg ÷ Q 12H
Diarrhea (5-12%), vomiting (2.5-8%), abd. pain (1.5-4%), rash (3-5%) Tablets Suspension
250, 500 125, 250
24.92
* Cost bases on a 10-day course of therapy for a 15-kg child. Suspensions and generic products were used when possible for pricing. Sources for average wholesale price, AWP: Whitmire Distribution Company, Dallas, TX, March 1994; AWP cost from Redbook Telephone Update 1995.
7. Treatment of AOM3,6
a. Amoxicillin is usually the initial therapy if the incidence of H. influenzae ß-lact+ is low and the child is not subject to recurrent AOM.
b. Other antimicrobial agents (e.g., amoxicillin-clavulanate or TMP-SMX if Group A Streptococcus is not believed to be the cause ) should be considered based on efficacy, cost (all aspects), compliance, dosage form availability, and adverse effects. Cefaclor offers adequate coverage but does not cover some strains of H. influenzae and M. catarrhalis. Other antimicrobials are considered secondary agents for AOM caused by resistant strains of H. influenzae and M. catarrhalis.
c. Duration of therapy
• Usually 10 days
• Study (Reference 7) has shown that 5 days of cefaclor was as effective as a 10 day course in patients with AOM with effusion.
• Currently looking at both shorter and longer courses of therapy.
d. Analgesics/antipyretics (e.g., acetaminophen)
8. Treatment of Persistent OM with Effusion following AOM
a. Another 10 day course of same antimicrobial
b. If the effusion persists, a second 10 day course of an alternate antimicrobial that is effective against BL+ organisms
c. Antihistamines or decongestants??
VII. Treatment of Various Other Types of OM
A. Treatment/prophylaxis of Recurrent AOM
1. Definition: child who has = 3 episodes of AOM in 6 months or 6 episodes over an 18 month period
2. Antimicrobial agent may be the same if it has not been used in previous 6 months
3. Antimicrobial prophylaxis8,9
a. Amoxicillin - 20 mg/kg/day divided BID or given as a once a day dose
b. Sulfisoxazole - 50 mg/kg/day divided BID or given as a once a day dose (considered second line drug because of adverse effect profile and decreased efficacy against Strep pneumoniae)
c. Myringotomy with tympanostomy tube placement should be considered.
d. Immunoprophylaxis - vaccines have not reduced incidence of OM.
B. Chronic OM with Effusion
1. Usually patients are asymptomatic except for effects on hearing.
2. Amoxicillin should be used first if the patient has not received the drug recently.
3. If the patient fails amoxicillin, use an alternate antimicrobial such as amoxicillin-clavulanate, cefaclor or cefuroxime axetil which are somewhat more effective than amoxicillin for OM with effusion.
4. Ten day course of antimicrobial vs. P. aeruginosa may be tried.
5. Myringotomy and tympanostomy tube insertion should be considered.
6. Adenoidectomy with or without tonsillectomy should be considered.
C. OM with Effusion in Neonates
1. Tympanocentesis may be needed to obtain middle ear fluid for culture and sensitivity.
2. Need to use an antimicrobial agent vs. Staph aureus and enteric gram (-) rods.
3. IV antimicrobial agents may be needed.
D. Chronic Suppurative OM
1. Tympanocentesis may be needed to obtain middle ear fluid for culture and sensitivity.
2. Common organisms include P. aeruginosa and Staph aureus.
3. IV antimicrobial agents may be needed for P. aeruginosa.
REFERENCES
1. Sagraves R, Maish W, Kameshka A. Update on otitis media. Part 1. Epidemiology and pathophysiology. Am Pharm 1992;12:27.
2. Sagraves R, Maish W, Kameshka A. Update on otitis media. Part 2. Treatment. Am Pharm 1993;33:29.
3. Sagraves R, Maish W. Therapy of acute otitis media. PharmacoEconomics 1994;6:202.
4. Klein JO. Epidemiology of otitis media. Pediatr Infect Dis J 1989;8:S9.
5. Giebink GS. Epidemiology and natural history of otitis media. In: Lim DJ, Bluestone CD, Klein JO, Nelson JD. Recent Advances in Otitis Media with Effusion. Philadelphia:BC Decker, Inc. 1984;5.
6. Richer M, LeBel M. Upper Respiratory Tract Infections. In: Pharmacotherapy, A Pathophysiologic Approach. 3rd edition. DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM (eds.). Elsevier Science Publishing, NY 1997; 2017-36.
7. Hendrickse WA, Kusmiesz H, Shelton S et al. Five vs ten days of therapy for acute otitis media. Pediatr Infect Dis J 1988;7:14.
8. McCracken GH, Jr. Management of acute otitis media with effusion. Pediatr Infect Dis J 1988;7:442.
9. Bluestone CD. Management of otitis media in infants and children: Current role of old and new antimicrobial agents. Pediatr Infect Dis J 1988;7:S129.
10. Wald ER. Changing trends in the microbiology of otitis media with effusion. Pediatr Infect Dis J 1984;3:380.
11. McCracken GH, Jr. Antimicrobial therapy for acute otitis media. Pediatr Infect Dis J 1984;3:383.
12. Ruuskanen O, Heikkinen T. Otitis media: etiology and diagnosis. Pediatr Infect Dis J 1994;13:S23.
13. Pichichero M. Assessing the treatment alternatives for acute otitis media. Pediatr Infect Dis J 1994;13:S27.
14. Giebink DM. Preventing otitis media. Ann Otol Rhinol Laryngol 1994;103:20.
15. Paparella MM, Schachern P. New developments in treating otitis media. Ann Otol Rhinol Laryngol 1994;103:7.
16. Schwinghammer TL. Update on otitis media and its treatment. Pharmacy Focus 1989;2:1.
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