AOMT: Changing incidence, changing pathogens

Acute otitis media is encountered every day, many times, in primary care. It remains the most common reason that a child will appropriately receive an antibiotic from a pediatrician or family physician, and it is the second most common reason for office visits after the common cold.¹

Changing pathogen dominance

In tracking the pathogens involved in AOM in children, research shows that the three dominant pathogens are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The relative proportions are changing in a dynamic way, though. Right now, about 40% of ear infections are caused by S. pneumoniae, about 40% to 45% are caused by H. influenzae, and the remainder are predominantly caused by M. catarrhalis.² Those same pathogens are the main culprits causing AOM with tympanostomy tubes, or AOMT, and are the same targets for antimicrobial therapy.

In the United States, the incidence of AOM has been changed since the introduction of the pneumococcal conjugate vaccine, PCV7,^2,3 and it is about to change again with the introduction of the expanded pneumococcal conjugate vaccine, PCV13, which incorporates additional otitis media–causing strains.

After the PCV7 vaccine came to market, for the first time H. influenzae surpassed S. pneumoniae as the dominant organism causing AOM in children in the United States.⁴ This change seemed clearly attributable to the widespread use of PCV7 vaccine. Three years later, resistant strains of pneumococcus, most importantly, type 19A, had emerged. In another study, a superbug strain of S. pneumoniae type 19A was shown to be resistant to all of the antibiotics licensed for approval to treat ear infections in children and was eradicated only through off-label use of levofloxacin, a fluoroquinolone antibiotic.⁵

This 19A strain now represents more than 50% of pneumococcal infections in the United States, and has caused the overall number of pneumococcal infections to increase.² The new PCV13 vaccine, licensed in February 2010, contains the 19A strain as an additional ingredient. With widespread use, I anticipate a dramatic reduction in pneumococcal otitis media, and my colleagues and I are leading a study to monitor ear pathogens in children in the PCV13 era. We expect another significant change in the pathogen mix of ear infections, both AOM and AOMT.

Recurrent AOM and the use of tympanostomy tubes

Signs and symptoms of AOM are nonspecific. They almost always occur in the context of the common cold with runny nose and cough. The child becomes irritable because of pain and pressure in the ears. He or she may cry and sleep restlessly. Infants in particular may cry while feeding because sucking increases pressure in the ears. At this point, parents often bring the child to the physician, who examines the ears and removes earwax from the ear canal. Although not pathognomonic, the best diagnostic feature for determining whether AOM is present is a bulging eardrum, independent of color or any other feature (Figure).⁶ If the eardrum is bulging, the physician can be highly confident that the patient has AOM, and with that bulging comes pain.

A child who experiences three episodes of otitis media within 6 months or four episodes within 12 months has recurrent AOM. The incidence of recurrent AOM is greatly influenced by a number of factors, most importantly attendance at daycare, which increases its incidence, and breast-feeding, which decreases its incidence.⁷ By and large, the literature suggests that among children who experience ear infections, between 15% and 25% will experience recurrent AOM.^8,9

The use of tympanostomy tubes for recurrent AOM has a long history in the United States where they have traditionally been implanted by ear, nose and throat surgeons for recurrent AOM. The insertion of tympanostomy tubes was performed under the premise that recurrent AOM could eventually lead to a number of significant adverse effects, including hearing loss or deafness, as well as delayed progress in school. The use of tubes has come under careful scrutiny in the last five to 10 years, and the indications for tympanostomy tube insertion is being reevaluated. In other countries, including developed countries of Western Europe, ear tube insertions are done much less frequently than in the United States. In some countries, only 10% to 20% of the total number of patients who receive tympanostomy tubes in the United States would receive the tubes if they lived elsewhere.^10,11 Regional patterns within the United States for likelihood to receive tympanostomy tube insertion are distinct, with children living in the Midwest and South more likely to get tubes than children living in the Northeast or West.¹⁰ White, non-Hispanic children are 82% more likely to have tubes placed compared with Africian-American children.¹⁰

From AOM to AOMT

In a study of New York City children who received tympanostomy tubes, the stated reason for surgery was recurrent AOM in 21%, otitis media with effusion in 60% and eustachian tube dysfunction in 11%.¹² Literature reviews show that 10% to 40% of patients who receive tympanostomy tubes and receive additional tympanostomy tube insertions will go on to experience further episodes of AOM.¹³ The tube then drains the purulent material containing otopathogens. Tympanostomy tubes increase the risks of otorrhea and antibiotic usage.¹⁴ However tubes also improve the quality of life, including physical suffering, hearing loss and caregiver concerns.¹⁵

In AOMT, fluid cannot build up behind an intact eardrum; instead, pus drains out of the tympanostomy tube. Parents are instructed to observe for this drainage, and if it appears, to instill antibiotic ear drops in the child. If the drainage does not subside after a few days, the parents may seek medical attention either from the primary care physician or from the specialist who inserted the tubes. At that time, a specimen may be taken for culture, but often an oral antibiotic is added to the treatment regimen.

Otitis media with effusion is a condition that may be confused with AOMT. Patients with otitis media with effusion develop a thick, almost glue-like fluid behind the eardrum, apparently in association with the eustachian tube, which serves as the natural drain of the middle ear space. The eardrum becomes inflamed and, consequently, the fluid that is made in the middle ear space builds up. Prolonged duration of this condition, which is considered to be three months in both ears or six months in a single ear, results in associated hearing loss of about 20 decibels, which translates into hearing muffled speech. A tympanostomy tube would be strongly considered as a treatment for these patients. Thereafter, in some of those children, the tubes will drain, not due to bacterial contamination, but rather because of overproduction of mucus in the middle ear space.

Treatment options

Evidence supports antibiotic treatment of AOMT. The first step should be an antibiotic ear drop—an advantageous option because there is no systemic absorption of the antibiotic, which increases bacterial resistance. Using a topical antibiotic ear drop results in minimal side effects and minimal impact on the ecology of the bacteria and the host that might otherwise encourage resistance among those bacteria in that particular person. Depending on the amount of fluid draining from behind the eardrum through the tube into the outer ear canal, however, a topical antibiotic drop may not be fully successful. The drops are instilled in the outer ear canal and must move in the opposite direction of the draining fluid, essentially moving upstream. If the patient has excessive draining, then an oral antibiotic may be necessary. Selection of an oral antibiotic is driven by the three main bacteria—S. pneumoniae, H. influenzae, and M. catarrhalis—and generally follows the guidelines issued by the American Academy of Pediatrics and the American Academy of Family Physicians, focusing on such drugs as high-dose amoxicillin, high-dose amoxicillin clavulanate and cefdinir.

Antibiotic treatment results differ between patients with AOMT and patients with AOM. With AOM, bacteria are in a closed space behind a sealed eardrum, unless the physician performs a tympanocentesis procedure, which is rare. An infection in this closed space has a heavy burden of bacteria that may not allow antibiotics to achieve a cure. One recent study showed that the common use of high-dose amoxicillin or high-dose amoxicillin clavulanate may not always succeed in that setting, not because of bacteria susceptibility, but rather because some children and adults do not absorb amoxicillin or amoxicillin clavulanate well.¹⁶ Blood levels in these patients are quite low, and consequently the levels in the ear behind a closed eardrum are correspondingly low, so a cure is not achieved. The success rate of topical and oral antibiotic treatment for patients with AOMT is generally higher than for patients with AOM because buildup in a closed space is rare, unless the tube becomes clogged with a high burden of bacteria.

Combination drop: Antibiotic and steroid

Some studies support the use of a combination ear drop that includes a steroid, and several key opinion leaders in the ear, nose and throat community endorse the addition of a steroid.

Some physicians have concerns about using drops that contain a steroid because they were educated to know that steroids have an adverse impact on the immunity system. Because physicians want the immunity system to work with the treatment, there is a misperception that a problem might emerge from steroid use. In fact, research to the contrary shows that steroids reduce the inflammation that occurs behind the tympanostomy tube, and it is that inflammation that facilitates the infection.¹⁷ Therefore, reducing inflammation with a local treatment will improve results.

Clinicians do not know exactly why children with tympanostomy tubes often develop AOMT. My colleagues and I at the Rochester General Research Institute are working on identifying immunological characteristics in these children that seem highly correlated with the development of AOMT. A large part may be genetically determined or corresponding with the maturity of the immune system. In some children, the maturation of the immune response is slower than in others, causing them to experience recurrent ear infections. The children then receive tympanostomy tubes and then experience ongoing drainage from the tubes. Although we do not have a therapy or preventive strategy to offer our patients and their families at the moment, we hope that our investigation will eventually produce some strong clues for the right direction to move in.

References

1. Grijalva CG, Nuorti JP, Griffin MR. Antibiotic prescription rates for acute respiratory tract infections in US ambulatory settings. JAMA. 2009; 302(7):758-766.
2. Casey JR, Adlowitz DG, Pichichero ME. New patterns in the otopathogens causing acute otitis media six to eight years after introduction of pneumococcal conjugate vaccine. Pediatr Infect Dis J. 2010;29:304-309.
3. Zhou F, Shefer A, Kong Y, Nuorti P. Trends in acute otitis media-related health care utilization by privately insured young children in the United States, 1997-2004. Pediatrics. 2008;121: 253-260.
4. Casey JR, Pichichero ME. Changes in frequency and pathogens causing acute otitis media in 1995-2003. Pediatr Infect Dis J. 2004;23:824-828.
5. Pichichero ME, Casey JR. Emergence of a multiresistant serotype 19A pneumococcal strain not included in the 7-valent conjugate vaccine as an otopathogen in children. JAMA. 2007;298:1772-1778.
6. Pichichero ME. Acute otitis media: Part I. Improving diagnostic accuracy. Am Fam Physician. 2000;61(7):2051-2056.
7. Sabirov A, Casey JR, Murphy TF, Pichichero ME. Breast-feeding is associated with a reduced frequency of acute otitis media and high serum antibody levels against NTHi and outer membrane protein vaccine antigen candidate P6. Pediatr Res. 2009;66(5):565-570.
8. Alho OP, Koivu M, Sorri M. What is an otitis prone child? Int J Pediatr Otolaryngol. 1991;21: 201-209.
9. Thompson D, Oster G, McGarry L, Klein J. Management of otitis media among children in a large health insurance plan. Pediatr Infect Dis J. 1999;18:239-244.
10. Kogan MD, Overpeck MD, Hoffman HJ, et al. Factors associated with tympanostomy tube insertion among preschool-aged children in the United States. Am J Public Health. 2000; 90(2):245-250.
11. Alho OP, Koivu M, Sorri M, Oja H, Kilkku O. Which children are being operated on for recurrent acute otitis media? Arch Otolaryngol Head Neck Surg. 1994;120(8):807-811.
12. Keyhani S, Kleinman LC, Rothschild M, et al. Clinical characteristics of New York City children who received tympanostomy tubes in 2002. Pediatrics. 2008;121(1): e24-33.
13. Boston M, McCook J, Burke B, Derkay C. Incidence of and risk factors for additional tympanostomy tube insertion in children. Arch Otolaryngol Head Neck Surg. 2003;129:293-296.
14. Ingels K, Rovers MM, van der Wilt GJ, Zielhuis GA. Ventilation tubes in infants increase the rise of otorrhoea and antibiotic usage. B-ENT. 2005,4:173-176.
15. Chow Y, Wabnitz DA, Ling J. Quality of life outcomes after ventilating tube insertion for otitis media in an Australian population. Int J Pediatr Otorhinolaryngol. 2007;71(10):1543-1547.
16. Pichichero ME, Reed M. Variations in amoxicillin pharmacokinetic/pharmacodynamic parameters may explain treatments failures in acute otitis media. Pediatr Drugs. 2009;11(4):243-249.
17. Alper CM, Dohar JE, Gulhan M, et al. Treatment of chronic suppurative otitis media with topical tobramycin and dexamethasone. Arch Otolarynogol Head Neck Surg. 2000;126:165-173.

Dr. Michael Pichichero is director of the Rochester General Hospital Research Institute in New York. Dr. Pichichero also practices at Legacy Pediatrics in Rochester and is a member of the Infectious Diseases in Children Editorial Board.

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