New guidelines on acute otitis media An overview of their key

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Clinical Professor of Pediatrics, University of Southern California and
   University of California,Los Angeles, Schools of Medicine,
  Los Angeles;and Kaiser Foundation Hospital, Panorama City, Calif.
Consultant,American Academy of Pediatrics Subcommittee on
   Management of Acute Otitis Media

New guidelines on acute otitis media:
An overview of their key principles for practice
       he proper management of acute otitis                                        mg/kg/day) vs standard-dose (40 mg/kg/day)
T      media (AOM) has received much                                               amoxicillin therapy?
attention in recent years.1 Studies have shown                                 • What is the efficacy of twice-daily vs
this condition to be overdiagnosed and,                                            thrice-daily therapy?
hence, overtreated as much 50% of the time                                     • What is the efficacy of short-term (3-, 5-,
by clinicians caring for children.2 The result-                                    or 7-day) vs long-term (10-day) therapy?
ing unnecessary use of antimicrobials and the                                  • What are the complications of AOM in
consequent increased prevalence of antibiotic                                      untreated children?
resistance was felt by the American Academy                                        To answer these questions, MEDLINE and
of Pediatrics (AAP) and the American                                           six other databases were searched for relevant
Academy of Family Physicians (AAFP) to                                         studies published between 1966 and March
warrant development of clear guidelines                                        1999. Approximately 3,500 citations were
defining the current status of expert opinion                                  reviewed, of which 760 considered the iden-                  AOM cannot
on the appropriate diagnosis and optimal                                       tified research questions; 74 of these were                  be diagnosed
management of AOM. This article summa-                                         randomized controlled trials that were felt to               without middle
rizes these new AAP/AAFP guidelines,3 focus-                                   be adequate to provide a database for resolu-
ing on five key principles they set forth, with                                tion of the key questions.                                   ear effusion—
the aim of laying the groundwork for the                                           The results of this search were published as             a red tympanic
roundtable discussion that follows.                                            an AHRQ monograph,4 which provided a                         membrane is
                                                                               basis for development of the AAP/AAFP
s HOW THE GUIDELINES TOOK SHAPE,                                               guidelines. Because the AAP/AAFP guide-                      not enough
  AND THE QUESTIONS THEY TOOK ON                                               lines were developed after completion of the
                                                                               literature review and publication of the
The AAP and AAFP developed the guide-
                                                                               monograph, they also include the results of
lines primarily by using data generated under a
                                                                               studies published through September 2003.
grant from the federal Agency for Healthcare
Research and Quality (AHRQ) through the
                                                                               s DEFINITION AND DIAGNOSIS OF AOM
Southern California Evidence-Based Practice
Center and the RAND Corporation.                                               The first portion of the guidelines deals with
   At the request of these groups, experts in                                  the definition of AOM. AOM is defined as
AOM were asked to identify the principal con-                                  the recent, abrupt onset (≤ 48 hours) of mid-
temporary questions in the diagnosis and treat-                                dle ear effusion accompanied by signs or
ment of AOM. More than 40 such questions                                       symptoms of inflammation of the middle ear.
were identified and prioritized. The following                                 Each of the three criteria of this definition—
seven were considered the most important:                                      (1) recent, abrupt onset; (2) presence of mid-
• What is the natural history of AOM?                                          dle ear effusion; and (3) presence of middle
• What is the outcome of AOM treated with                                      ear inflammation—is necessary to establish
   antimicrobials vs no antimicrobial therapy?                                 the diagnosis. It is often disregarded that mid-
• What is the efficacy of amoxicillin com-                                     dle ear effusion is a sine qua non: without it
   pared with that of other antimicrobials?                                    there can be no diagnosis of AOM. A red
• What is the efficacy of high-dose (80 to 90                                  tympanic membrane is not enough.

                                            C L EV E L A ND C LI N I C J OU RN AL O F M E DI C I N E   V O L U ME 7 1 • SUP PL E M EN T 4   J U N E 2 0 04   S3
                          GUIDELINES OV E R V I E W                         MARCY

                          The guidelines are limited to considera-                       Obtaining a seal is often quite difficult, if not
                       tion of uncomplicated AOM—that is, AOM                            impossible, especially in children younger
                       limited to the middle ear cleft—in otherwise                      than 6 months of age.
                       healthy children from 2 months to 12 years of                        Acoustic reflectometry has been advocat-
                       age. While it is recognized that the guidelines                   ed as a simpler way of establishing the pres-
                       may also apply to older children and adoles-                      ence of middle ear fluid. In contrast to tym-
                       cents, the published studies reviewed for                         panography, it does not require a seal and can
                       development of the guidelines are almost all                      also be performed through even a small open-
                       limited to this age group.                                        ing in the cerumen in the external auditory
                                                                                         canal. Acoustic reflectometry is a very useful
                       Principle 1:                                                      diagnostic method and should become
                       To reliably diagnose AOM, the clinician should                    increasingly available over the next few years
                       confirm a history of abrupt onset (≤ 48 hours) of                 as it is improved and distributed more widely.
                       middle ear effusion and inflammation                                 Pneumatic otoscopy is the most practical
                                                                                         diagnostic modality for AOM. The pneumat-
                       This principle is based on the perceived need                     ic otoscope should be checked to assure that
                       to improve the diagnosis of AOM. The diag-                        the bulb is current and the light is bright and
                       nosis can be suspected clinically when the                        white in color. If a yellow or orange bulb is
                       signs and symptoms of an upper respiratory                        used, the tympanic membrane will appear
                       tract infection, which frequently precedes                        inflamed. The otoscope should be checked
                       AOM by 3 to 5 days, are accompanied by ear                        regularly to assure that there is appropriate
                       pain, irritability, or pulling at the ear. It is                  pressure to move the tympanic membrane
                       important to note, however, that pulling at                       when it is pumped, that a tight seal can be
Up to 50% of           the ear is an unreliable sign, as no more than                    applied, and that appropriate speculi are used
                       10% of children who pull at the ear actually                      to obtain a good seal in the external auditory
cases of otitis        have AOM. Fever is generally less than 40°C,                      canal.
media with             and one third of children with AOM who
effusion are           present in the physician’s office have no                         An emphasis on diagnostic accuracy
                       fever at all. Purulent drainage is, of course,                    One of the guidelines’ main goals is to
misdiagnosed           diagnostic.                                                       improve the accuracy with which clinicians
as AOM                                                                                   evaluate the presence or absence of AOM.
                       Technical diagnostic aids                                         Pichichero and Poole2 have shown clearly
                       In addition to clinical signs and symptoms,                       that a large proportion of children diagnosed
                       certain technical aids can assist in the diagno-                  with AOM instead have otitis media with
                       sis of AOM: tympanocentesis, tympanogra-                          effusion. As many as 50% of such cases are
                       phy, reflectometry, and pneumatic otoscopy.                       misdiagnosed or overdiagnosed as AOM.
                          Tympanocentesis is indicated when rapid                            Studies done in 1993 by Karma (reviewed
                       bacteriologic diagnosis and antimicrobial sus-                    in 1998 by Pelton5) examined tympanic
                       ceptibility are necessary. This includes the                      membranes and used tympanocentesis to
                       treatment of children with underlying                             establish the presence or absence of infec-
                       immune deficits, such as those receiving                          tion. These studies identified certain findings
                       chemotherapy; children with mastoiditis,                          that were highly correlated with AOM:
                       meningitis, or other intracranial complica-                       • A bulging tympanic membrane had a posi-
                       tions; and children in whom two or three                             tive predictive value of 83% to 99%
                       sequential courses of appropriate antimicro-                      • Distinctly impaired mobility in the pres-
                       bial therapy have failed.                                            ence of tympanic membrane fullness or
                          Tympanography is quite valuable in defin-                         bulging had a positive predictive value of
                       ing the presence of middle ear effusion,                             85% to 99%
                       which is an absolute prerequisite for the diag-                   • Redness of the tympanic membrane alone,
                       nosis of AOM. However, tympanography can                             without other findings, had a predictive
                       be difficult to perform, particularly in a young                     value as low as 7%.
                       febrile or otherwise uncooperative child.                             This demonstrates that the old paradigm,

  S4   C LEV E LA N D C L IN I C J OU RN AL O F M ED I CI N E   VO LU ME 7 1 • S U P PL EM E N T 4   J U N E 2 0 04
“Chief complaint: earache; physical examina-                  TABLE 1
tion: red tympanic membrane; Rx: amoxicillin,”
is simply no longer adequate or acceptable.                      Observation vs antibiotic thera p y :
These guidelines now make it imperative                          When to use each in children with
that the position of the tympanic membrane                       acute otitis media (AO M )
and its mobility both be described when clin-                     AGE OF            IF DIAGNOSIS OF            IF DIAGNOSIS
icians attempt to make a diagnosis of AOM.                        CHILD             AOM IS CERTAIN             IS UNCERTAIN

s HOW TO ADDRESS PAIN                                             < 6 mo            Antibiotic                 Antibiotic
Principle 2:                                                      6 mo –2 yr        Antibiotic                 Antibiotic if severe
The management of AOM should include assess-                                                                   illness; observe if
ment of pain. If pain is present, the clinician                                                                nonsevere illness
should provide treatment to reduce it.                            ≥ 2 yr            Antibiotic if severe       Observe
                                                                                    illness; observe if
A number of options for pain management                                             nonsevere illness
are available in addition to acetaminophen,
ibuprofen, and naproxen, including codeine,
benzocaine drops, and myringotomy. Co-
deine may be used in certain cases, such as in              placebo or no therapy and children receiving
older children, children who are not lethar-                antimicrobials.7,8 Questions have been raised
gic, children who are free of productive                    about the validity of these data, since it was
cough or wheeze, and children with reliable                 recognized that many of the children diag-
parents. The codeine may be given together                  nosed with AOM may well have had otitis
with acetaminophen to provide further anal-                 media with effusion, as previously noted.                          Observation
gesic effect. Benzocaine drops have very mar-               Also, many of the children studied belonged
                                                            to relatively older age groups—older than 2                        without
ginal efficacy.6 Myringotomy can be used for
the child who is in extreme pain, as it pro-                years in some cases, and older than 1 year in                      antibiotics may
vides almost immediate relief.                              many cases—calling into question the validi-                       be considered
    The utility of homeopathic medicines,                   ty of using observation alone in younger chil-
                                                            dren. The median age of children with AOM                          under certain
osteopathic or chiropractic manipulation,
and topical naturopathic agents requires con-               is approximately 12 months, and since there                        circumstances
firmation. Use of home remedies such as                     is a large number of children with AOM
putting warm oil in the ear canal (if otorrhea              around that age, the studies that involved
is absent), applying heat over the ear, and dis-            those children should be considered the most
traction have stood the test of time and offer              appropriate for reference.
little or no risk.
                                                            Most patients will respond to symptomatic
s TO OBSERVE OR NOT TO OBSERVE?                             therapy
                                                            Looking at overall response rates, approxi-
Principle 3a:
                                                            mately two thirds of children with AOM will
Observation without antibiotics is an appropriate
                                                            respond to symptomatic treatment alone at
option for selected children with uncomplicated
                                                            24 hours, approximately 85% will respond at
AOM based on diagnostic certainty, age, severity
                                                            2 to 3 days, and approximately 90% will
of illness, and certainty of follow-up
                                                            respond at 4 to 7 days.7 Treatment, when
Observation without antibiotic therapy is an                compared with symptomatic therapy, is more
option clinicians may consider under certain                favorable in only 4% of children overall at 2
circumstances, as outlined in Table 1 . This                to 3 days; however, children under 2 years of
principle is based on data generated over the               age appear to be at a selective disadvantage,
last decades documenting the clinical resolu-               since observation alone fails in almost 25% of
tion of otitis media among children given                   children in this age group with severe illness
placebo or no therapy and on studies compar-                (see below).9 As expected, there is no statisti-
ing response between children receiving                     cally significant difference between antimi-

                           C LE VE LA N D C L IN IC J OU R N AL O F M ED I CI N E       V O LU M E 7 1 • SU P P L EM E N T 4   J U N E 2 0 04   S5
                           GUIDELINES OV E R V I E W                          MARCY

                        TAB LE 2                                                             TAB LE 3
                            M i c robiology of acute otitis                                     Suggested antimicrobial
                            media                                                               t h e rapy for acute otitis media
                                                                 CASES IN WHICH                 • Amoxicillin 80 to 90 mg/kg/day in two
                                                                  THE ORGANISM                    divided doses for 5 to 10 days, depending on
                            ORGANISM                               IS CAUSATIVE
                                                                                                  patient age
                            Haemophilus influenzae                35%–50%                       • For patients with non–type I or uncertain
                                                                                                  allergy to beta-lactams: cefdinir, cefuroxime,
                            Streptococcus pneumoniae              25%–40%
                                                                                                  or cefpodoxime
                            Moraxella catarrhalis                   5%–10%
                                                                                                • For patients with anaphylaxis or severe allergy
                            Viruses                                 5%–15%                        to beta-lactams: azithromycin,clarithromycin,
                                                                                                  trimethoprim ± sulfamethoxazole,
                            No growth of bacterial agents           1%–15%                        erythromycin-sulfisoxazole
                                                                                                • For patients with vomiting or uncertain
                                                                                                  compliance, ceftriaxone 50 mg/kg IM
                        crobial treatment and symptomatic therapy
                        at 24 hours, given that 24 hours is required
                        for antimicrobials to have an effect on the
                        bacteria and for there to be a diminution in                        by viral infection in early reports. Given this
                        the inflammatory response, which is responsi-                       microbiology, a wide variety of antimicrobials
                        ble for both the middle ear effusion and the                        are available for the treatment of AOM.
Observation alone       discomfort that accompany AOM.
                           The observation option has certain limita-                       s NAVIGATING ANTIBIOTIC CHOICES
fails in nearly 25%
                        tions and certain provisions (Table 1).                             Principle 3b:
of children under       Patient age, certainty of the diagnosis, and                        If the decision is made to treat with an antibiotic,
2 years of age          severity of illness should determine the                            amoxicillin remains the initial antibiotic of choice
with severe AOM         course of therapy. “Severe” illness is defined                      for most children
                        as illness in which the child’s temperature is
                        39 °C or higher or there is moderate or severe                      This recommendation is based on the recog-
                        otalgia. Children with mild ear pain and a                          nition that amoxicillin is not only effective
                        temperature less than 39°C are considered to                        but also has a low incidence of side effects, is
                        have “nonsevere” illness.                                           cost-effective, and, by virtue of its taste, helps
                                                                                            to assure good compliance.
                        The microbiology of AOM                                                The suggested antimicrobial therapy for
                        translates to broad therapy choices                                 AOM is outlined in Table 3 . High-dose
                        The antimicrobial therapy of AOM depends,                           amoxicillin (80 to 90 mg/kg/day) is to be
                        of course, on the microbiology of the infec-                        given in two divided doses for 5 to 10 days,
                        tion (Table 2). In recent years, there has                          depending on patient age. Children who
                        been an appreciation of the rising incidence                        have uncertain allergy to beta-lactams or
                        of nontypable Haemophilus influenzae as an                          nonanaphylactic allergy are advised to take
                        etiology of AOM. At present, 35% to 50% of                          an oral cephalosporin, such as cefdinir,
                        cases of AOM are caused by nontypable H                             cefuroxime, or cefpodoxime. Although these
                        influenzae, 25% to 40% by Streptococcus pneu-                       three oral cephalosporins have equal micro-
                        moniae, and 5% to 10% by Moraxella catar-                           biologic efficacy, there are no clinical studies
                        rhalis.3 A negligible number of cases are due                       comparing their efficacy. However, there is
                        to other bacteria. Viruses have been identi-                        every reason to believe that they are equally
                        fied as the sole cause of infection in 5% to                        effective clinically. Cefdinir is more palat-
                        15% of cases.10 No growth of bacterial agents                       able, as demonstrated in a palatability study
                        has been found in 1% to 15% of cases;3 this                         in adults,11 and thus is more likely to result in
                        finding may be attributable to AOM caused                           good compliance.

   S6   C LE V E LA ND CL I N IC J OU R N AL O F M ED I C IN E    V O LU ME 7 1 • S UP P L E M EN T 4   JU N E 2 0 04
   Children with a history of anaphylaxis or                TA B L E 4
severe allergy to beta-lactams warrant treat-
ment with one of the following: azithro-                        Antimicrobial therapy for children who
mycin, clarithromycin, trimethoprim-sulfa-                      do not respond to initial management
methoxazole, or erythromycin-sulfisoxazole.                     at 48 to 72 hours
                                                                • Amoxicillin-clavulanate 90 mg/kg/day in two divided
Concerns about resistance guide                                   doses (to 4 g),* or
amoxicillin dosing                                              • Cefdinir, cefuroxime, or cefpodoxime, or
The rationale for use of high-dose amoxi-
cillin (80 to 90 mg/kg/day) is to provide drug                  • Ceftriaxone 50 mg/kg intramuscularly or intravenously,
levels in the middle ear fluid adequate to                        three daily doses
eradicate strains of S pneumoniae that are
                                                                *Can be primary therapy for children with moderate to severe otalgia
fully susceptible to penicillin as well as
                                                                 or fever ≥ 39 ºC.
strains that are nonsusceptible, which repre-
sent approximately 25% of all pneumococci
isolated from middle ear fluid nationally. The              s WHAT TO DO WHEN INITIAL
susceptibility pattern is geographically                      MANAGEMENT FAILS
dependent, with some centers reporting non-
susceptibility in 60% of strains while others               Principle 4:
report it in as few as 15%. Moreover, one                   Lack of response within 48 to 72 hours requires
third to one half of nonsusceptible strains are             reassessment to confirm AOM. If confirmed
highly resistant to penicillin.                             in a child initially managed with observation,
   Higher drug levels in the middle ear fluid               an antibiotic should be prescribed. If initial
will eradicate not only the susceptible organ-              management was with an antibiotic, an
isms but also those of intermediate resistance,             alternative antibiotic should be prescribed.
                                                                                                                              to second-line
which are defined as pneumococci for which                  Reassessment may be accomplished either by
the minimum inhibitory concentration                        reevaluation in the office or, when the relia-                    therapy should
(MIC) of penicillin is between 0.12 and 1                   bility of the observer is known to the physi-                     be considered for
µg/mL. Resistant organisms, for which the                   cian and felt to be adequate, by telephone dis-                   tympanocentesis
MIC is greater than 2 µg/mL, would also                     cussion. These telephone discussions should
largely be eradicated by the higher doses, and              be well documented in the patient’s chart.
there are few resistant organisms for which                    Table 4 provides recommendations for
the MIC of penicillin is greater than 8 µg/mL.              appropriate therapy after failure of first-line
   Giving amoxicillin in two, rather than                   therapy. Amoxicillin-clavulanate 90 mg/kg/day
three, divided doses will assure yet higher                 should be given in two divided doses up to 4 g.
middle ear fluid levels of the drug. The dura-              Because the clavulanate moiety causes the
tion of therapy depends on patient age, and                 gastrointestinal adverse effects associated with
the guidelines reflect the fact that few data               this agent, if this higher dose of amoxicillin-
exist on short-course therapy in younger chil-              clavulanate is used, it is recommended that
dren. Thus, it is recommended that short-                   the new 14-to-1 formulation, rather than the
course amoxicillin therapy be limited to chil-              7-to-1 formulation, be prescribed. This can
dren 6 years of age or older, for whom 5 to 7               also be accomplished by diluting amoxicillin-
days may suffice.                                           clavulanate with equal parts of amoxicillin.
                                                            Alternative therapy includes the oral cephalo-
Another option for selected children                        sporins cefdinir, cefuroxime, or cefpodoxime,
For children who are vomiting or for whom                   or ceftriaxone 50 mg/kg/day given intramuscu-
compliance cannot be assured, ceftriaxone                   larly or intravenously for three daily doses.
50 mg/kg given as a single intramuscular dose
can be considered appropriate therapy. In                   Further failure calls for tympanocentesis
such cases, no additional oral therapy is                   or cautious use of clindamycin
required and, if conjunctivitis is present, no              Children who do not respond to second-line
additional ocular therapy is required.                      therapy should be considered for tympan-

                          C LEV E LA N D C L IN I C J OU RN AL O F M ED IC I N E     VO LU ME 7 1 • SUP PL EM E N T 4         J U N E 2 0 04   S7
                          GUIDELINES OV E R V I E W                        MARCY

          TAB LE 5                                                                      recurrent AOM (this also applies if the child’s
                                                                                        father had a history of recurrent AOM).
             Strategies for preventing acute otitis                                         Elimination of supine bottle-feeding, elim-
             media through risk-factor reduction                                        ination of exposure to tobacco smoke in the
             • Breast-feed rather than bottle-feed                                      household, and elimination of pacifier use
                                                                                        may also reduce the incidence of AOM.
             • Eliminate supine bottle-feeding
                                                                                            For children who attend day care centers,
             • Eliminate exposure of the child to tobacco smoke                         particularly large centers, it may be ideal for
              • Eliminate pacifier use                                                  the parents to seek smaller groups or elimi-
                                                                                        nate day care entirely if their work schedules
             • Modify group day care activities                                         or economic conditions permit.
             • Provide the child with influenza and pneumococcal                            Influenza vaccination, either with the par-
               conjugate vaccinations                                                   enteral formulation12 or with the new cold-
                                                                                        adapted intranasal vaccine,13 has been shown
             • Have the child investigated for atopy and immunodeficiency               to reduce the overall incidence of AOM in
                                                                                        children by approximately 30% during the
                                                                                        influenza season. A more recent study, howev-
                    ocentesis, particularly if they have persistent                     er, could find no efficacy of killed vaccine in
                    symptoms that are concerning to the clini-                          preventing AOM during influenza season in
                    cian, persistently high fever, or persistent                        children 6 to 23 months of age.14 The recent
                    severe pain. Therapy can then be adjusted on                        recommendation by the Advisory Committee
                    the basis of Gram stain results and subse-                          on Immunization Practice to immunize all
                    quently fine-tuned on the basis of culture and                      children over 6 months of age with influenza
Overuse of          susceptibility studies, which will, however,                        vaccine eliminates the specific intent of using
clindamycin         not become available for 48 to 72 hours.                            the vaccine for prevention of AOM.
                        If tympanocentesis is not available (or                             Immunization with pneumococcal conju-
clearly will reduce while the results of susceptibility studies are                     gate vaccine has been shown to reduce the
its future utility awaited), use of clindamycin should be con-                          incidence of AOM by varying degrees.
                    sidered. High-dose amoxicillin-clavulanate,                         Although the incidence of AOM caused by
                    as second-line therapy, will have eradicated                        those serotypes present in the vaccine is sig-
                    not only the beta-lactamase–positive H                              nificantly decreased, the overall effect of the
                    influenzae and M catarrhalis but also S pneumo-                     vaccine on the incidence of AOM is quite
                    niae that may have escaped treatment during                         limited. A large HMO study found a 6%
                    the first regimen using high-dose amoxicillin                       reduction in the incidence of AOM,15 a 7.8%
                    alone. Of the remaining organisms, the most                         reduction in the frequency of office visits due
                    likely would be highly resistant S pneumoniae,                      to AOM, and a 6% reduction in antibiotic
                    of which approximately 93% to 95% of organ-                         prescriptions.16 A subsequent Finnish study,
                    isms remain susceptible to clindamycin.                             while also noting a mean 6% reduction in
                    Overuse of clindamycin clearly will reduce its                      AOM incidence, reported confidence inter-
                    utility in the future, so clinicians are cau-                       vals around the mean of less than 1.0, indi-
                    tioned to restrict its use only to children who                     cating the possibility of no efficacy at all.17
                    do not respond to second-line therapy.                              Although the reduction in the overall inci-
                                                                                        dence of single episodes of AOM is marginal,
                      s ADVICE FOR REDUCING THE RISK OF AOM                             it is clear that the use of pneumococcal con-
                                                                                        jugate vaccine will reduce both the incidence
                      Principle 5:
                                                                                        of recurrent AOM (ie, five cases or more)
                      Clinicians should encourage AOM prevention
                                                                                        and the incidence of the need for tympanos-
                      through reduction of risk factors
                                                                                        tomy tubes by 20% to 25% annually.15,16
                      This includes encouraging breast-feeding over                         Children who have recurrent AOM
                      bottle-feeding, particularly among mothers                        should be investigated for allergy and
                      who have had other children with recurrent                        immunodeficiency. However, children with
                      AOM or who themselves had a history of                            immunodeficiency will rarely present with

  S8   C LE VE LA ND CL IN IC J OU R N AL O F M ED I CI N E   V O LU M E 7 1 • S U P P L EM EN T 4   JU N E 2 0 04
recurrent AOM alone; they usually have an                             s A ROLE FOR ALTERNATIVE MEDICINE?
increased frequency and severity of other
upper or lower respiratory tract infections and                       No recommendations can be made at this
other infections.                                                     time regarding complementary or alternative
   Strategies for reducing risk factors for                           medicine for AOM, given the limited and
AOM are summarized in Table 5 .                                       controversial data currently available.

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                                                                                                                                             for typanostomy

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