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COVER ARTICLE/CME Urgent Care 2(9):20, 2007 Because otopathogens have changed, so has the treatment for acute otitis media. The author presents the latest information on how to recognize and treat this common childhood illness, including what antibiotics are currently recommended. Acute otitis media (AOM) is the second most common diagnosis, after viral respiratory infection, in children presenting to urgent care clinics. Most patients with AOM are between six months and three years old, and urgent care physicians prescribe antibiotics for AOM more than for any other childhood illness. In this article, I will discuss the latest diagnostic criteria for otitis media, new otopathogens, and current treatments. NEW DIAGNOSTIC CRITERIA The recent revisions in diagnostic criteria for AOM arose from a better understanding of the changes that occur in the middle ear space when a viral upper respiratory infection is present and from evidence-based research. In the new diagnostic paradigm for AOM, a bulging or full (not reddened) tympanic membrane is the critical factor. New research in animals and humans shows that otalgia results from a change in the position of the tympanic membrane that can be caused by AOM, otitis media with effusion (OME), or a simple cold. When a patient has an upper respiratory infection and the nose becomes congested, the eustachian tube also becomes congested. With the eustachian tube closed, the air normally present in the middle ear space escapes by diffusion across the tympanic membrane, causing it to retract. This change in position can produce ear discomfort or even pain, similar to what occurs during air travel with cabin pressurization and depressurization. Goblet cells in the middle ear mucosa normally keep the middle ear space moist, but when the eustachian tube is blocked, mucus builds up and is unable to drain through the blocked tube, causing OME, which may be symptomatic or asymptomatic. In some cases, negative pressure in the middle ear space allows virus- and bacteria-laden mucus in the posterior nasopharynx to reflux through the eustachian tube and enter the middle ear space. Once there, these organisms usually elicit an inflammatory response, with migration of white blood cells to the site. As cytokines and other inflammatory mediators are released, a positive pressure builds up and the tympanic membrane bulges—the cardinal feature of AOM. This inflammatory response eventually subsides (more quickly with antibiotics than without) and OME is once again left in the middle ear space. When the eustachian tube finally relaxes as the inflammation along its isthmus subsides, the fluid in the middle ear space drains and the pathogenic process is over. Recent studies have pinpointed which findings on an ear examination correlate best with the isolation of bacterial otopathogens. No finding correlates better with bacterial AOM than a bulging tympanic membrane. A new key finding is that the classic red tympanic membrane is actually a very poor predictor of true AOM (see table below). During the examination, first note the position of the tympanic membrane and then observe its translucency or opacification. Next, record its color and finally note its mobility using a pneumatic otoscope.
Don’t be lulled into thinking that otalgia along with an upper respiratory infection equals AOM. As noted above, otalgia occurs from a stretched tympanic membrane—either positively stretched due to AOM or negatively stretched due to simple upper respiratory infections or OME, or both. New research attempting to correlate various AOM symptoms with an increased likelihood of the disease has shown poor sensitivity and specificity for symptoms we traditionally associate with AOM. Again, the best way to accurately diagnose AOM is to get good visualization of the tympanic membrane and determine if it is bulging. To do this, first remove the wax. I recommend using a soft plastic ear wax spoon. If this fails, irrigate the external auditory canal with warm water using a large syringe or water-pick. For hard wax, instill carbamide peroxide or triethanolamine polypeptide or hydrogen peroxide in the ear canal, wait 10 to 20 minutes, then irrigate. CHANGING PATHOGENS The widespread use of the 7-valent pneumococcal conjugate vaccine (PCV7) over the past five years has led to a shift in the predominant otopathogens. This vaccine contains the seven most common strains of pneumococci that cause AOM. During the 1970s, 1980s, and 1990s, the most frequently isolated bacterial pathogen in AOM was Streptococcus pneumoniae. In the 1990s, penicillin-resistant strains multiplied. All that changed in 2001 when PCV7 came into widespread use in the United States. In 2004, our group in Rochester, New York, and another group from rural Kentucky simultaneously reported the following important changes in the pathogen mix of American children with AOM: Subsequent studies by our group, in collaboration with groups in Pittsburgh and Vienna, Virginia, have shown that nontypeable H. influenzae remains the most frequently isolated otopathogen (see graph below). However, replacement serotypes of pneumococci not contained in PCV7 have started to emerge, causing an increase in pneumococcal isolations. These strains are quickly becoming penicillin-resistant. Moraxella catarrhalis remains the third most common AOM isolate (2% to 10% of cases); this organism always produces beta lactamase.
TREATMENT RECOMMENDATIONS In updating its guidelines on preferred antibiotics for treating AOM, the American Academy of Pediatrics (AAP) Committee on Infectious Diseases used pharmacokinetics (PK) and pharmacodynamics (PD) as a major tool. The first two tables below show the rank order of potency of various antibiotics against S. pneumoniae and H. influenzae using the PK/PD model. Pharmacokinetics and pharmacodynamics data were combined with high-quality clinical trial results to produce a list of recommended antibiotics that would work best against both S. pneumoniae and H. influenzae as empiric therapy. The committee issued the latest guidelines in 2006 and endorsed six antibiotics for treatment of AOM, listed alphabetically in the bottom table below. These six antibiotics were also endorsed by the AAP and the American Academy of Family Physicians (AAFP) in their 2004 guidelines.
Note that standard doses of amoxicillin (40 mg/kg, three times daily) and amoxicillin/clavulanate (45 mg/kg, twice daily) aren’t listed among the recommended drugs. This is because recent studies have found that penicillin resistance among pneumococci can be overcome by doubling the amoxicillin dose from 40 to 50 mg/kg a day to 80 to 100 mg/kg a day. Also, trimethoprim/sulfamethoxazole is no longer recommended because of its poor activity against beta lactamase- Only three oral cephalosporins are recommended—cefuroxime, cefpodoxime, and cefdinir. Ceftriaxone is also recommended, but only in a three-dose schedule of 50 mg/kg administered on sequential days. The macrolides azithromycin and clarithromycin are recommended only for patients with severe penicillin allergy, such as an episode of anaphylaxis, not just a rash or urticaria. Macrolides have poor activity against H.
influenzae, and a recent analysis shows that the rate of crossreactivity of cephalosporins in the penicillin-allergic patient has been grossly overstated. In fact, the rate of an allergic reaction to a first-generation cephalosporin like cephalexin is only about 0.5%, and the rate of an allergic reaction to a second- and third-generation cephalosporin is essentially zero. Thus, guidelines endorse second- or third-generation cephalosporins for the penicillin-allergic patient. These new antibiotic recommendations reflect an evidence-based approach to identifying preferred antibiotics. These recommendations should be followed, except in special circumstances—and the reason for not adhering to them should be clearly documented in the medical
record. For example, if a patient has AOM with conjunctivitis, the most likely bacteria is H. influenzae, so using ceftibuten or cefixime would be reasonable. The 2004 AAP/AAFP guidelines and the 2006 AAP Red Book recommend 80 to 100 mg/kg of amoxicillin daily as the treament of choice. In the dose specified, this drug should eradicate most pneumococci and about half of H. influenzae. Thus, it should work in about 70% of patients. Amoxicillin/clavulanate is the preferred choice to maintain the activity of amoxicillin and add beta lactamase stability. This drug should work in about 85% of patients. The three preferred cephalosporins—cefuroxime, cefpodoxime, and cefdinir—aren’t quite as active as amoxicillin against pneumococci but are very active against beta lactamase-producing H. influenzae. These drugs should work in about 80% of patients. If one antibiotic fails in the treatment of AOM, choose the second most effective drug on the list. When selecting a subsequent treatment, use the former treatment as your guide and choose a drug with a higher likelihood of success. For example, a patient who fails to improve on amoxicillin might be treated with amoxicillin/clavulanate or a preferred oral cephalosporin, or a patient who doesn’t get better on an oral cephalosporin might be treated with amoxicillin/clavulanate or three injections of ceftriaxone. On the other hand, a patient who isn’t improving on amoxicillin/clavulanate or who took the drug within the past 30 days without improvement shouldn’t be treated subsequently with amoxicillin or a single injection of ceftriaxone. Three shots of ceftriaxone are the strongest drug and dose—your “ace in the hole,” so to speak. Don’t prescribe it unless all other recommended drugs have failed. It should work in 70% of patients after one dose and 95% of patients after three sequential doses. DURATION OF TREATMENT The duration of antibiotic treatment for AOM has also been revised. The AAP recommends the option of five days of therapy for children older than two years. This change reflects accumulated data and meta-analyses showing no difference in outcomes when shortened courses (generally five days) of antibiotics are used. Several papers also document the common knowledge that most parents discontinue their child’s 10-day antibiotic regimen after four or five days, when the child begins feeling better, and then save the remaining drug for future use. In an effort to reduce antibiotic use, the AAP issued AOM treatment guidelines in 2004 that included an option to observe select children without giving antibiotics. This wait-and-see approach advised simple pain management for two to three days to allow the infection to subside on its own. The guidelines specifically recommend appropriate doses of acetaminophen or ibuprofen and consideration of benzocaine ear drops for the following children: those older than age two (a marker for reasonable verbal skills to explain their symptoms), those with a fever less than 102°F, and those with mild otalgia. The observation option is contingent on close follow-up in case the patient’s condition worsens. If your urgent care clinic doesn’t provide follow-up care, observation isn’t an option. Instead, urge the child’s parents to visit their primary care physician. Follow-up examinations are also important for infants and children who can’t yet talk to tell you if they feel better. They should be seen by a primary care physician after completing antibiotic treatment for AOM, especially children being managed for AOM treatment failure. THREE TYPICAL CASES The following cases illustrate the points covered in the article. Case #1: A 3-year-old boy presents to your urgent care clinic with an upper respiratory infection, a temperature of 100°F, and a complaint of earache in his right ear. Examination finds a bulging tympanic membrane with purulent fluid behind it. You confirm the diagnosis of AOM and ask the child how much his ear hurts. He says, “A little.” You tell his mother: “He has a mild ear infection but I think he can fight it off on his own. Let me give you a prescription for amoxicillin (90 mg/kg divided twice daily, with an expiration date three days away). You can fill it if his pain gets worse. In the meantime, give him ibuprofen according to package directions and fill this prescription for benzocaine ear drops. Give the ear drops as often as needed for pain. If you fill the amoxicillin prescription, be sure to see your primary care physician.” Case #2: A 10-month-old girl presents to your urgent care clinic with an upper respiratory infection. She’s tugging on her left ear, and her temperature is 101°F. Examination finds purulent fluid behind the tympanic membrane, which is bulging slightly. You confirm the diagnosis of AOM and ask the mother if the child has a history of ear infections. She says yes, at age one month and six months, but they were treated with amoxicillin successfully. You tell her, “Let’s treat this with amoxicillin (80 to100 mg/kg divided twice daily). It’s our first line of treatment and it has worked before. She should feel better in two days, but if she doesn’t, see your primary care physician. In fact, even if she seems better, see him in about three weeks, because sometimes ear infections smolder and the child seems mostly okay, but the infection isn’t gone.” Case #3: An 18-month-old boy presents to your urgent care clinic with an upper respiratory infection and a temperature of 102°F. He’s crying excessively. Examination finds purulent fluid behind a bulging tympanic membrane. You confirm the diagnosis of AOM and learn from the mother than this is the child’s third episode of AOM, with the last diagnosis only three weeks ago. The mother explains that the first episode was treated successfully with amoxicillin (80 to 100 mg/kg twice daily). The second episode didn’t improve after 10 days of amoxicillin but did respond to 10 days of amoxicillin/clavulanate. This third episode was treated three weeks ago by their primary care physician with amoxicillin/clavulanate (80 to 100 mg/kg twice daily). You tell her: “This is most likely a resistant bacteria. If amoxicillin/clavulanate didn’t work, we need to give him a shot of ceftriaxone (50 mg/kg) and have you see your primary care physician tomorrow, because he’ll need two more shots to have the best chance for a cure.” KEEPING CURRENT Only viral respiratory infections present more often in urgent care clinics than AOM. It is imperative that urgent care clinicians keep current on the changes in the diagnostic criteria and new treatment recommendations for this common childhood illness.
Suggested Reading
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