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Wise Use of Antibiotics

July, 2018

Approach to the Treatment of Acute Otitis Media
 

Rana El Feghaly, MD, MSCI | Director, Outpatient Antibiotic Stewardship Program; Associate Professor of Pediatrics, University of Missouri-Kansas City School of Medicine

Following the March issue of The Link newsletter where we discussed the role of watchful waiting in the management of acute otitis media, or AOM, this article will focus on the best approach to treating a child with AOM, using the American Academy of Pediatrics guidelines as a guiding document.

Symptomatic management and watchful waiting


Spontaneous cure in AOM is common; occurring in 50-80 percent of Moraxella catarrhalis cases, 50 percent of nontypeable Haemophilus influenzae cases, and 20 percent of Streptococcus pneumoniae cases.2 Therefore, it’s important to recognize children who may benefit from the watchful waiting or the delayed prescription approach. Those are children 6 months to 23 months of age with unilateral mild AOM (fever <39oC, no or mild otalgia with onset < 48 hours), and children older than 2 years of age with unilateral or bilateral mild symptoms.1 Assessing and treating pain is a very important aspect of AOM management, as is assuring follow-up within 48-72 hours if watchful waiting is offered.

Antimicrobial therapy


Treatment of any infectious condition should take into account the disease severity, patient’s age, commonly implicated organisms, local antibiogram, and antimicrobial’s pharmacokinetics and pharmacodynamics. As a general rule, for beta-lactams, the goal is for the time above the minimum inhibitory concentration (MIC) of the antibiotic in the milieu where the infection needs to be treated to be higher than 40 percent. In other words, the antibiotic’s concentration needs to be higher than the organism’s MIC for at least 40 percent of the time between dosing intervals for the antibiotic to be effective. Adding to this, only 10-15 percent of many beta-lactams actually reach the middle ear, which makes reaching this time above the MIC (T>MIC) even more challenging. 

First-line therapy: amoxicillin


High-dose amoxicillin remains the first-line option when antibiotic treatment is necessary for AOM. Amoxicillin penetrates the middle ear fairly well. It also provides excellent coverage for Streptococcus pneumoniae, and for non-beta lactamase producing Haemophilus influenzae and Moraxella catarrhalis. The high dose (80-90 mg/kg/day divided in BID dosing) ensures that high enough levels are reaching the middle ear for providing an adequate T>MIC for even penicillin-intermediate Streptococcus pneumoniae. Amoxicillin is generally tolerable, with few side effects, making it an ideal first-line therapy option.3

For the child who has recently received amoxicillin in the prior 30 days, amoxicillin-clavulanate is the preferred option to broaden coverage to beta-lactamase producing Moraxella catarrhalis and Haemophilus influenzae. If the child presents with concomitant conjunctivitis, Haemophilus influenzae becomes higher on the differential, and amoxicillin-clavulanate would therefore be the initial antibiotic option. 

Role of oral cephalosporins


Oral second- and third-generation cephalosporins should be reserved for penicillin allergic patients. In a study conducted at Colorado Children’s Hospital comparing the activity of amoxicillin and oral cephalosporins on penicillin-susceptible Streptococcus pneumoniae, it was evident that time above the MIC of cefdinir was inferior to all other antibiotics tested (8 percent for 14 mg/kg once daily, 12.5 percent for 7 mg/kg twice daily, and 21 percent for 15 mg/kg twice daily), compared to 33.3-50 percent for high-dose amoxicillin, 33.3 percent for cefpodoxime and 25 percent for cefuroxime.4 Cefdinir is poorly absorbed (only 16-25 percent of the oral dose is absorbed) and is highly bound to protein (60-70 percent), making it a suboptimal choice for treatment of AOM. To put this in perspective, amoxicillin is ~100 percent absorbed and is only 17-20 percent bound to proteins reaching high levels in the middle ear fluid.5 Therefore, cefdinir should not be reserved for patients who fail initial antibiotic therapy with amoxicillin or amoxicillin-clavulanate, but could be considered, along with cefuroxime or cefpodoxime, for the treatment of an initial AOM in children with documented allergy to amoxicillin. It is important to mention here that, while 10-15 percent of the population may be labeled as penicillin allergic, only a minority of those with the label actually have a true allergy … but that’s a topic for another Link article!

Treatment failures


If the infection fails to resolve with amoxicillin therapy, three days of ceftriaxone or high-dose amoxicillin-clavulanate could be offered, as coverage for pneumococcus is retained, and beta-lactamase producing Haemophilus influenzae and Moraxella coverage are provided. An alternative would include clindamycin (with or without the use of an oral cephalosporin). If the child does not improve with amoxicillin/clavulanate, then three days of ceftriaxone is recommended. In that setting, a second/third generation cephalosporin is listed as an option, along with clindamycin.1 Such combination therapy has palatability issues and may increase the risk for Clostridium difficile infection. 

References:

1. The Diagnosis and Management of Acute Otitis Media. Lieberthal AS, Carroll AE, Chonmaitree T, Ganiats TG, Hoberman A, Jackson MA, et al.Pediatrics. 2013;131(3):e964-99.
2. The "In vivo Sensitivity Test"--Bacteriology of Middle Ear Exudate, During Antimicrobial Therapy in Otitis Media. Howie VM, Ploussard JH.Pediatrics. 1969;44(6):940-4.
3. Bacteriologic and Clinical Efficacy of High-Dose Amoxicillin for Therapy of Acute Otitis Media in Children. Piglansky L, Leibovitz E, Raiz S, Greenberg D, Press J, Leiberman A, et al. Pediatr Infect Dis J. 2003;22(5):405-13.
4. The Infamous Oral Cephalosporins – A Step Up or a Step Down? Hurst A, Rounds A, Child J, Parker S. Children's Hospital Colorado Contagious Comments. 2017;32(1).
5. Cephem Antibiotics: Wise Use Today Preserves Cure for Tomorrow. Parker S, Mitchell M, Child J. Pediatr Rev. 2013;34(11):510-23; quiz 23-4.