Amoxicillin-clavulanate, intramuscular Ceftriaxone or alternatively Clindamycin with or without a third generation cephalosporin can be used for otitis media that fails amoxicillin therapy.
Beta-lactam antibiotics such as cephalosporins and penicillins target cell wall proteins called penicillin binding proteins. Streptococcus pneumoniae can develop resistance to beta-lactams through modification of this protein. Most strains remain susceptible to high dose oral amoxicillin. More resistant strains can be are covered by a second or third generation cephalosporin or clindamycin.
Around half of H influenzae isolates from otitis media cases produce a beta-lactamase making them resistant to amoxicillin. These strains would be covered by Amoxicillin-clavulanate or a second or third generation cephalosporin.
M catarrhalis uniformly produces a beta-lactamase creating resistance to amoxicillin though the natural history of M catarrhalis is less severe than other pathogens.
Initially therapy is typically with amoxicillin, when this fails therapy that broadens coverage especially in regards to beta-lactamase producing organisms is indicated. This can be with Amoxicillin-clavulanate or intramuscular Ceftriaxone. Alternatively Clindamycin with or without a third generation cephalosporin is an option for failed amoxicillin.
Lieberthal AS, Carroll AE, Chonmaitree T, Ganiats TG, Hoberman A, Jackson MA, Joffe MD, Miller DT, Rosenfeld RM, Sevilla XD, Schwartz RH, Thomas PA, Tunkel DE. The diagnosis and management of acute otitis media. Pediatrics. 2013 Mar;131(3):e964-99. PMID: 23439909