Otitis Media

Definition of Acute OM

A diagnosis of AOM requires:

Random Points

• Clinical history alone is poorly predictive of the presence of AOM, especially in younger children
• Acoustic reflectometry can be helpful, because it requires no seal of the canal and can determine the presence of middle-ear fluid through only a small opening in the cerumen

Otalgia

• The management of AOM should include an assessment of pain. If pain is present, the clinician should recommend treatment to reduce pain. Treatments for otalgia.

Watchful Waiting

About 80% of otherwise healthy kids with acute otitis media get better without antibiotics. The American Academy of Pediatrics and American Academy of Family Physicians now recommend "watchful waiting" for some kids.

• They say to hold off antibiotics for 2 to 3 days to see if they're really necessary.
• Watchful waiting is generally appropriate for children 2 years and older with mild symptoms.
• It's NOT appropriate for babies under 6 months...or ANY child with moderate to severe pain or fever over 102˚F. These kids usually need antibiotics.
• Have parents give acetaminophen or ibuprofen if needed for pain...whether or not the child is getting an antibiotic.
• Criteria for Initial Antibacterial-Agent Treatment or Observation in Children With AOM

Placebo-controlled trials of AOM over the past 30 years have shown consistently that most children do well, without adverse sequelae, even without antibacterial therapy. By 24 hours, 61% of children have decreased symptoms whether they receive placebo or antibacterial agents. By 7 days, approximately 75% of children have resolution of symptoms. Watchful waiting and mastoiditis; current evidence does not suggest a clinically important increased risk of mastoiditis in children when AOM is managed only with initial symptomatic treatment without antibacterial agents. Clinicians should remain aware that antibacterial-agent treatment might mask mastoiditis signs and symptoms, producing a subtle presentation that can delay diagnosis. The potential of antibacterial therapy at the initial visit to shorten symptoms by 1 day in 5% to 14% of children can be compared with the avoidance of common antibacterial side effects in 5% to 10% of children, infrequent serious side effects, and the adverse effects of antibacterial resistance. If there is worsening of illness or if there is no improvement in 48 to 72 hours while a child is under observation, institution of antibacterial therapy should be considered.

  (From PEDIATRICS Vol. 113 No. 5 May 2004, pp. 1451-1465)

Therapy

Common Pathogens:

• Strep pneumoniae: 25-50% (decreasing) (resistance: altered PBP)
• H. flu (nontypable):  15-30% (increasing)  (resistance: B-lactamase) **update: now H. flu is the most common**
  • in a nine-year, prospective study conducted by Pichichero, Janet Casey, MD, and colleagues, researchers followed 551 children with acute otitis media to examine whether the causative pathogens in persistent AOM had changed in frequency or distribution following the introduction of high-dose amoxicillin therapy and pneumococcal conjugate vaccination.
    Results indicated that “H. influenzae has become the predominant pathogen of persistent AOM and AOM treatment failure since universal immunization with the pneumococcal conjugate vaccine [PCV7, Prevnar, Wyeth].” The researchers added that more Streptococcus pneumoniae AOM isolates are becoming penicillin resistant again and more H. influenzae are beta-lactamase–producing.
    In another 2007 study conducted by Casey et al, data suggested an emergence in non-PCV7 serotypes since 2003; 80% were penicillin-resistant.
    “Although the current AAP/AAFP guidelines endorse amoxicillin high dose (90 mg/kg/day), the better antibiotic selection would be amoxicillin/clavulanate high dose, or if tolerability is an issue, then one of the AAP/AAFP–recommended cephalosporins,” Pichichero said.
  • Published in Infectious Diseases in Children February 2009
• moraxella catarrhalis 3-20% (resistance: B-lactamase)
• Viruses have been found in resp secr and/or MEE in 40-75% of AOM (RSV, rhino-, corona-, parainfluenza, adeno, enterovirus) - may be responsible for many cases of abx failure

The results favoring standard 10-day therapy have been most significant in children younger than 2 years and suggestive of increased efficacy in those 2 to 5 years of age. Thus, for younger children and for children with severe disease, a standard 10-day course is recommended. For children 6 years of age and older with mild to moderate disease, a 5- to 7-day course is appropriate. Stepwise pattern (if one fails, try the next): 

1. watchful waiting
2. amoxicillin 80-90 mg/kg/d^a
3. amox-clavulanate: 90 mg/kg/d amox (start here for temp >39 or severe otalgia)^{b (consider OMNICEF (cefdinir))}
4. A patient who fails amoxicillin-potassium clavulanate should be treated with a 3-day course of parenteral ceftriaxone because of its superior efficacy against S pneumoniae, compared with alternative oral antibacterials
5. If AOM persists, tympanocentesis should be recommended to make a bacteriologic diagnosis.
6. 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 additional therapy
7. Special cases
   • non-type I allergic reaction to penicillins: cefdinir, cefpodoxime, cefuroxime
   • type I reactions: azithromycin^c, clarithromycin, erythromycin-sulfisoxazole*, sulfamethoxazole-trimethoprim* (*resistance is substantial, not recommended for failure w/ amox)
   • vomiting, unable to PO: ceftriaxone 50mg/kg IV/IM qdx3 (1 or 3 day regimen)

a.The justification to use amoxicillin as first-line therapy in most patients with AOM relates to its general effectiveness when used in sufficient doses against susceptible and intermediate resistant pneumococci as well as its safety, low cost, acceptable taste, and narrow microbiologic spectrum. Only S pneumoniae that are highly resistant to penicillin will not respond to conventional doses of amoxicillin. Accordingly, approximately 80% of children with AOM will respond to treatment with high-dose amoxicillin, including many caused by resistant pneumococci. The higher dose will yield middle-ear fluid levels that exceed the minimum inhibitory concentration of all S pneumoniae that are intermediate in resistance to penicillin and many, but not all, highly resistant S pneumoniae. Risk factors for the presence of bacterial species likely to be resistant to amoxicillin include attendance at child care, recent receipt (less than 30 days) of antibacterial treatment, and age younger than 2 years.

b. This dose has sufficient potassium clavulanate to inhibit all ß-lactamase-producing H influenzae and M catarrhalis. Note: per Sept 2004 Pediatric news, 3rd gen cephalosporins cefdinir (better tasting, once/day) and cefpodoxime (bad tasting) are highly effective against H. flu and other B-lactamase producing organisms, and have less gastrointestinal upset.

c. Sept 2004 Pediatric news: because of PCV7 vaccination, there is an upward trend of H. flu infection in response to the decrease in strep. Standard doses of azithro has marginal B-lactamase coverage, but recent data suggest that a double dose of azithromycin 20/kg/d x 3d, is as effective as augmentin in kids < 2yo and under w/ persistent or recurrent AOM.  (Antimicrob. Agents Chemother. 47[10]:3179-86, 2003).

Persistent Middle Ear Effusion

Persistent MEE after resolution of acute symptoms is common and should not be viewed as a need for active therapy. OME must be differentiated clinically from AOM and requires additional monitoring but not antibacterial therapy. Assurance that OME resolves is particularly important for children with cognitive or developmental delays that may be impacted adversely by transient hearing loss associated with MEE.

• Two weeks after an episode of AOM, 60% to 70% of children have MEE
• 1 month after: 40%
• 3 months: 10% to 25% after 3 months.

Prevention

• breastfeeding for at least the first 6 months also seems to be helpful against the development of early episodes of AOM
• Avoiding supine bottle feeding ("bottle propping")
• reducing or eliminating pacifier use in the second 6 months of life
• eliminating exposure to passive tobacco smoke
• Pneumococcal conjugate vaccines have proven effective in preventing vaccine-serotype pneumococcal otitis media, but their overall benefit is small, with only a 6% reduction in the incidence of AOM

Source:
CLINICAL PRACTICE GUIDELINE
Diagnosis and Management of Acute Otitis
Media Subcommittee on Management of Acute Otitis Media
PEDIATRICS Vol. 113 No. 5 May 2004, pp. 1451-1465

Antibiotic Resistance

• There are two major forms of antibiotic resistance currently.
• The primary mode of resistance for Streptococcus pneumoniae is alteration in the penicillin-binding protein site. This may be overcome by use of high-dose amoxicillin.
• Bacterial resistance can also occur to beta-lactam antibiotics such as penicillin, amoxicillin, and ampicillin by production of beta-lactamases, enzymes that inactivate the antibiotic by disrupting the beta-lactam ring. Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus are the three most common beta-lactamase-producing pathogens affecting children.
   
• Because Streptococcus pneumoniae causes a higher proportion of cases of acute otitis media than beta-lactamase- producing bacteria, it makes sense to use high-dose amoxicillin as first-line therapy.
• If the acute otitis media does not resolve with high-dose amoxicillin, as described for the child in the vignette, the infection may be due to a beta-lactamase-producing organism, which requires the use of a beta-lactamase-resistant antibiotic, such as amoxicillin- clavulanate (or cefdinir (omnicef))
   
• Clindamycin, a lincosamide, and cephalexin, a first-generation cephalosporin, do not have activity against either H influenzae or M catarrhalis.
• Because the patient in the vignette is still symptomatic after 3 days of therapy, he has experienced treatment failure. Thus, continued high-dose amoxicillin is not indicated.
• Although azithromycin may be effective against H influenzae, amoxicillin-clavulanate remains the drug of choice for those who have clinically failed treatment with high-dose amoxicillin. Recent pneumococcal surveillance studies indicate resistance to erythromycin at approximately 10%. Substantial cross-resistance between erythromycin and beta-lactam agents exists. Therefore, patients who have already failed amoxicillin treatment are more likely to have macrolide-resistant infections as well. 

References:
Baquero F, Loza E. Antibiotic resistance of microorganisms involved in
ear, nose and throat infections. Pediatr Infect Dis J. 1994;13(suppl
1):S9-S14
Dowell SF, Butler JC, Giebink GS, et al. Acute otitis media:
management and surveillance in an era of pneumococcal
resistance—report from the Drug-resistant Streptococcus pneumoniae
Therapeutic Working Group. Pediatr Infect Dis J. 1999;18:1-9
Dowell SF, Marcy SM, Phillips WR, Gerber MA, Schwartz B. Otitis
media—principles of judicious use of antimicrobial agents. Pediatrics.
1998;101(suppl):S165-S171
Rosenfeld RM, Vertrees JE, Carr J, et al. Clinical efficacy of
antimicrobial drugs for acute otitis media: metaanalysis of 5400
children from thirty-three randomized trials. J Pediatr.
1994;124:355-367

• Pichichero ME. New research in otitis media and sinusitis 2008. Presented at: 21st Annual IDC NY Symposium; Nov. 22-23, 2008; New York.
• Pediatr Infect Dis J. 2004;23:824-828.
• JAMA. 2007;298:1772-1778.