This algorithm is for those with Acute Otitis Media (AOM) in ages 2 months to 12 years.

Otitis media is the leading indication for use of outpatient antibiotics in the United States. Identifying patients who are likely to benefit from antimicrobial therapy is an important step in the appropriate treatment of otitis media.

A first step is correctly distinguishing Acute Otitis Media (AOM) from Middle Ear Effusion (MEE) as the treatment differs by diagnosis.

Criteria for Diagnosing AOM (need to meet 1, 2 and 3):

1. Recent, usually abrupt, onset of signs and symptoms of middle-ear inflammation and effusion
2. The presence of middle-ear effusion that is indicated by any of the following:
• Bulging of the tympanic membrane
• Limited or absent mobility of the tympanic membrane
• Air-fluid level behind the TM
• Otorrhea
3. Signs or symptoms of middle-ear inflammation as indicated by either:
• Distinct erythema of the TM
• Distinct otalgia (discomfort clearly referable to the ear that results in interference with normal activities or sleep)

Discussion of Drug Resistant Streptococcus Pneumoniae (DRSP) is an ongoing area of contention and one that is evolving with the use of Pneumococcal Conjugate Vaccine (Prevnar®). In children immunized with Prevnar® who are under 2 years of age; a reduction of 98% was noted in DRSP. As a result of this vaccine; there has been a shift toward other serotypes of S. Pneumoniae (from the 7 covered by the vaccine) which have typically not been penicillin resistant. In immunized children, the rate of AOM being caused by H. influenzae has increased from 43% (pre-Prevnar®) to 57% (post-Prevnar®).

Although formal guidelines by prominent groups has yet to evolve, based upon these data; it would appear as though immunized children are at higher risk of H. influenzae and at low risk of DRSP. This data may affect choice and dosing of antibiotics. It is also important to note that most AOM resolves by itself; and antibiotics only impact a small number of those treated.

Risks for having DRSP

• Recent antibiotic usage
• Age <2 years or >65 years
• Attends daycare
• Immunosuppression
• Multiple medical comorbidities

Drug comparison in treating DRSP (for AOM)

MIC-90 = The concentration where 90% of isolates tested will have inhibition of growth

Antimicrobial Treatment of AOM (AAFP/AAP):

• First choice in patients not allergic to penicillin (PCN) with mild to moderate AOM
• Amoxicillin 80-90 mg/kg/day, PO divided BID (maximum dose 2-3 grams/day)
• Note that in patients who have been immunized with Prevnar® that risk of DRSP is minimal and routine dose amoxicillin should be effective for most strains of S. pneumoniae. In this group, >50% of bacterial cases, a beta-lactamase resistant organism is likely (H. influenza or M. catarrhalis); it is not unreasonable to focus therapy on non-penicillin resistant streptococcus, H. influenza and M. catarrhalis (Consider Amoxicillin-clavulanate, cefdinir, cefpodoxime, cefuroxime)
• First choice in patients not allergic to PCN with severe illness or suspected H. influenza or M. catarrhalis
• Amoxicillin-clavulanate (Augmentin® or Augmentin ES®) 90 mg/kg/day, PO divided BID (maximum 3600 mg/day) [either use amoxicillin-clavulanate 45 mg/kg/day PLUS amoxicillin 45 mg/kg/day OR use Augmentin ES® formulation]
• These recommendations are based upon an assumption of DRSP being likely; however, in patients who have been immunized with Prevnar®, DRSP is unlikely, and standard dose (45 mg/kg/day PO divided BID) Amoxicillin-clavulanate may be considered
• For cases with mild PCN allergy (not anaphylaxis or hives) the following options should be selected from:
• Cefdinir (Omnicef®) 14 mg/kg/day, PO divided QD or BID (maximum 600 mg/day)
• Cefpodoxime (Vantin®) 10 mg/kg/day, PO given QD (maximum 800 mg/day)
• Cefuroxime (Ceftin®) 30 mg/kg/day, PO divided BID (maximum 1000 mg/day)
• For cases with Type I PCN allergy (anaphylaxis or hives), the following options should be selected from:
• Azithromycin (Zithromax®) [select 1 option]
• 10 mg/kg/day PO × 3 days (maximum 500 mg/day)
• 10 mg/kg PO on day 1 (maximum 500 mg) then 5 mg/kg/day PO QD × 4 days (maximum 250 mg/day)
• 30 mg/kg PO × 1 dose (maximum 1500 mg)
• Clarithromycin (Biaxin®) 15 mg/kg/day, PO divided BID (maximum 1000 mg/day) (15 mg/kg per day in 2 divided doses)
• Erythromycin-sulfisoxazole (Pediazole®) 50 mg/kg/day, PO divided TID/QID (maximum 2000 mg/day based upon erythromycin component)
• Sulfamethoxazole-trimethoprim (Septra®/Bactrim®) 6-10 mg/kg/day, PO divided BID (maximum 320 mg/day based upon trimethoprim component)
• Alternative therapy in the penicillin-allergic patient who is being treated for infection that is known or presumed to be caused by penicillin-resistant S pneumoniae is Clindamycin 30-40 mg/kg/day, PO divided TID (maximum 1200 mg/day)
• In the patient who is vomiting or cannot otherwise tolerate oral medication, a single dose of Ceftriaxone (Rocephin®) 50 mg/kg IM/IV has been shown to be effective for the initial treatment of AOM
• Duration of therapy:
• <6 years = 10 days
• Any age with severe disease = 10 days
• >=6 years (mild/moderate infection) = 5-7 days

Important diagnostic/treatment considerations:

• Distinguish between AOM and MEE
• Assess and treat pain as part of care for AOM
• Observation with just treatment of pain and no antibiotics is an option for 48-72 hours in:
• Those 6 months - 2 years who have a non-severe presentation AND it is unclear whether AOM truly is present
• Those >2 years with a non-severe presentation OR when it is unclear whether AOM truly is present
• In patients observed who are not improving within 48-72 hours, the patient should be reassessed and the diagnosis of AOM confirmed. If AOM is confirmed, antimicrobial therapy is initiated
• If a patient fails to respond to initial antibiotic therapy within 48-72 hours; the patient should be reassessed and the diagnosis of AOM confirmed and a change in antimicrobial agent made
• Where H. influenzae is the pathogen 50% are expected to be beta-lactamase positive (will require antibiotic with beta-lactamase inhibitor)
• Where M. catarrhalis is the pathogen 100% are expected to be beta-lactamase positive (will require antibiotic with beta-lactamase inhibitor)

Progression of treatment (initially observed)

• If the patient was treated with initial observation, amoxicillin should be started at a dose of 80 to 90 mg/kg/day
• The exceptions (as listed below) should be treated with Amoxicillin-clavulanate (90 mg/kg/day, PO divided BID):
• Severe illness (moderate to severe otalgia or temperature 39°C or higher)
• Patients suspected to have need for additional coverage for ß-lactamase positive organisms (H. influenzae and M. catarrhalis)

Progression of treatment (patients who have been treated initially with Amoxicillin and didn't improve):

• High-dose amoxicillin-clavulanate (90 mg/kg per day of amoxicillin component, with 6.4 mg/kg per day of clavulanate in 2 divided doses)should be used
• Alternatives in patients with a history of a non-type I allergic reaction to penicillins are cefdinir, cefpodoxime, or cefuroxime
• In cases of type I reactions, alternatives are azithromycin, clarithromycin, erythromycin-sulfisoxazole, or sulfamethoxazole-trimethoprim
• Ceftriaxone (50 mg/kg per day), given for 3 consecutive days, either intravenously or intramuscularly, can be used in children with vomiting, or in other situations that preclude administration of oral antibacterial agents
• In the treatment of AOM unresponsive to initial antibacterial therapy, a 3-day course of ceftriaxone has been shown to be better than a 1-day regimen
• Although trimethoprim-sulfamethoxazole and erythromycin-sulfisoxazole have traditionally been useful as first and second line therapy for patients with AOM, recent data indicates that these are probably not optimal choices when a patient fails to improve while receiving amoxicillin
• A patient who fails amoxicillin-clavulanate should be treated with a 3-day course of parenteral ceftriaxone due to its superior efficacy against S. pneumoniae compared with alternative oral antibacterials
• When DRSP is present, a single dose of ceftriaxone has a failure rate of 53%, whereas 3 days of therapy has failure of just 5%
• A single dose of ceftriaxone is completely effective when non-DRSP is the cause
• If AOM persists, tympanocentesis should be recommended to make a bacteriologic diagnosis
• If tympanocentesis is not available, a course of clindamycin may be considered for the rare case of penicillin-resistant pneumococcal infection not responding to the previous regimens
• If the patient still does not improve, tympanocentesis with Gram stain, culture, and antibacterial agent sensitivity studies of the fluid is essential to guide further therapy
• Use of an advanced fluoroquinolone such as levofloxacin (Levaquin®), gatifloxacin (Tequin®) or moxifloxacin (Avelox®) are effective 3^rd line choices as they have virtually 100% activity against the causative pathogens. However, it must be noted, that although these agents have been used in the pediatric population; they are not formally approved and no current major guidelines have formally recommended these agents
• One study showed levofloxacin (Levaquin®) to be safe and highly effective in treating 204 high risk children (80% being <=2 years) with 10 mg/kg/dose PO given BID × 10 days

References:

• American Academy of Pediatrics Subcommittee on Management of Acute Otitis Media. Diagnosis and management of acute otitis media. Pediatrics. 2004;113(5):1451-65.
• Arguedas A, Dagan R, Pichichero M, et al. An open-label, double tympanocentesis study of levofloxacin therapy in children with, or at high risk for, recurrent or persistent acute otitis media. Pediatr Infect Dis J. 2006;25(12):1102-9.
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• Brunton S, Pichichero ME. Acute otitis media: influence of the PCV-7 vaccine on changes in the disease and its management. J Fam Pract. 2005;54(11):961-8.
• Kyaw MH, Lynfield R, Schaffner W, et al. Effect of introduction of the pneumococcal conjugate vaccine on drug-resistant Streptococcus pneumoniae. N Engl J Med. 2006;354(14):1455-63.
• O'brien KL, Santosham M. Potential impact of conjugate pneumococcal vaccines on pediatric pneumococcal diseases. Am J Epidemiol. 2004;159(7):634-44.
• Segal N, Leibovitz E, Dagan R, Leiberman A. Acute otitis media-diagnosis and treatment in the era of antibiotic resistant organisms: updated clinical practice guidelines. Int J Pediatr Otorhinolaryngol. 2005;69(10):1311-9.
• Soley C, Arguedas A, Porras W, et al. In vitro activities of levofloxacin and comparable agents against middle ear fluid, nasopharyngeal, and oropharyngeal pathogens obtained from Costa Rican children with recurrent otitis media or failing other antibiotic therapy. Antimicrob Agents Chemother. 2005;49(7):3056-8.
• Thomas AR. Judicious use of antibiotics (Second edition). http://public.health.oregon.gov/PreventionWellness/SafeLiving/AntibioticResistance/Documents/pdfs/cme2.pdf Last accessed June 24, 2013.