Clinical Practice
This Journal feature begins with a case vignette highlighting with bacteria.4-6 Tympanocentesis has revealed Strep-
a common clinical problem. Evidence supporting various tococcus pneumoniae in 20 to 35 percent of patients
strategies is then presented, followed by a review of formal with acute otitis, nontypable Haemophilus influenzae
guidelines, when they exist. The article ends with the in 20 to 30 percent, Moraxella catarrhalis in 20 per-
authors clinical recommendations. cent, no bacteria in 20 to 30 percent, and virus with or
without bacteria in 17 to 44 percent.5-7
OTITIS MEDIA STRATEGIES AND EVIDENCE
Diagnosis
J. OWEN HENDLEY, M.D.
The two requirements for a diagnosis of acute oti-tis
media are inflammation of and fluid in the middle
An otherwise healthy 17-month-old boy had a ear.8,9 A retracted drum (Fig. 2A), which may be pain-
cold accompanied by two days of rhinorrhea, ful, is due to negative middle-ear pressure and not to
cough, and fever (temperature of up to 38.8C bacteria. Bacterial otitis media is characterized by a
[102F]). On day 5 he became fussy and woke up bulging eardrum that has purulent fluid behind it (Fig.
crying multiple times during the night. The fol- 2B)10,11 or by purulent otorrhea after the tympan-ic
lowing day he was afebrile, and a physical exam- membrane has been perforated. Otitis media with-out a
ination was normal except for findings of slight bulging tympanic membrane, which is usually called
redness of the left tympanic membrane with no acute otitis media, is much more common. In-
middle-ear fluid and a bulging right tympanic flammation of the middle ear may be signified by local
membrane with white fluid behind it obscuring the or systemic findings such as ear pain, erythema of the
umbo. How should this child be treated? tympanic membrane, fever, and cold symptoms. 8,9 A
red tympanic membrane without middle-ear fluid (Fig.
THE CLINICAL PROBLEM 2C) is not acute otitis. Acute otitis must also be
Otitis media, or inflammation of the middle ear, is distinguished from otitis media with effusion, which is
diagnosed more than 5 million times per year in the defined as fluid in the middle ear without local or
United States; it is the most common reason for the systemic illness.
prescription of antibiotics in children. The diagnosis of
otitis is usually followed by antibiotic treatment Antibiotic Therapy
despite a woeful lack of substantial evidence on the Once acute otitis, which may be viral, bacterial, or
question of antibiotic therapy for this condition.1 both, has been diagnosed, the central issue is whether
Otitis media usually follows a viral infection of the antibiotic therapy will be in the childs best interest (Table
nasopharynx that disrupts the function of the eusta-chian 1). A meta-analysis12 of randomized, placebo-controlled
tubes. Tubal dysfunction severe enough to im-pair trials found that acute otitis had resolved at one week in
ventilation and produce transient negative middle-ear 81 percent of placebo recipients, as com-pared with 94
pressure on tympanometry was found to occur during 66 percent of antibiotic recipients (an ab-solute difference of
percent of colds in schoolchildren2 and 75 percent of 13 percent). More recent analyses have yielded similar
colds in children in day care.3 In patients with colds, findings.9,13 In general, the rates of clinical resolution
bacteria and viruses from the nasopharynx that reach the were similar in placebo and antibi-otic recipients on the
middle ear during pressure equilibration may be cleared first day of therapy but slightly higher at three to five days
by the mucociliary system (Fig. 1) less effectively than and at seven days among those who received antibiotic
usual. Bacteria may replicate in fluid in the middle ear to therapy.14,15 Amoxicil-lin is as effective as any other drug
cause bacterial otitis media; respira-tory viruses may or drugs,12,16 even though at least one quarter of S.
infect the middle-ear mucosa, either alone, leading to pneumoniae strains have increased resistance to penicillin
viral otitis media, or in combination and amoxicillin, one quarter to one third of H. influenzae
strains are resistant in vitro to amoxicillin (that is, are b-
lacta-masepositive), and virtually all strains of M.
From the Division of Pediatric Infectious Diseases, University of Virginia catarrha-lis are resistant to amoxicillin (b-lactamase
Health System, Charlottesville. Address reprint requests to Dr. Hendley at the
Division of Pediatric Infectious Diseases, University of Virginia Health positive). The clinical effect of a single dose of
System, Charlottesville, VA 22908, or at joh@virginia.edu. ceftriaxone or
N Engl J Med, Vol. 347, No. 15 October 10, 2002 www.nejm.org 1169
Aditus
Mucociliary
epithelium
Mastoid air
cells Eustachian
tube
Lateral wall of
nasopharynx
Middle-ear
space
Tympanic
membrane
5 days of azithromycin was not different from the ef- Fluid clears by three months in 90 percent of children
fect of 7 to 10 days of amoxicillin.9 whether or not they received antibiotics.12,18 A meta-
Whether antibiotic therapy reduces the risk of pro- analysis of randomized trials found that two to four
longed illness in children six months to two years of weeks of antibiotic therapy for otitis media with effu-
age was examined in a trial comparing amoxicillin and sion had a small, but consistent, transient effect on re-
placebo in 240 children in the Netherlands, where the sidual fluid.19 At one month there was an absolute dif-
background rates of resistance to amoxicillin are 1 ference in the rates of resolution of 16 percent in favor
percent for S. pneumoniae and 6 percent for H. in- of antibiotic therapy, but there was no difference in the
fluenzae.17 About a third of the patients had bulging or proportions of children who had residual fluid at three
perforated tympanic membranes. Otitis was more months.
prolonged in children two years of age or younger than
Resistant Otitis Media
in older children in other studies, but antibiotic therapy
had a limited effect, reducing the incidence of Resistant bacterial otitis media is recognized by the
persistent symptoms by 13 percent on day 4 and persistence of fever, otalgia, and red, bulging tympan-
shortening the duration of fever by one day. ic membranes or by persistent otorrhea after three or
Fifty percent of children have middle-ear fluid for a more days of antibiotic therapy. 20,21 Culture of puru-
month after the resolution of acute otitis, regardless of lent fluid yielded bacteria that were resistant to the
whether they received antibiotic or placebo.12,14,18 prescribed antibiotic in only one third of cases.20,22
1170 N Engl J Med, Vol. 347, No. 15 October 10, 2002 www.nejm.org
A B C
CONDITION TREATMENT
Otitis media with bulging tym- Immediate treatment with high-dose amoxicillin (80100
panic membrane mg/kg of body weight per day orally) for 7 days*
Otitis media without bulging Delayed antibiotic-prescribing strategy
tympanic membrane
Recurrent acute otitis media Delayed antibiotic-prescribing strategy
Immunization with influenza vaccine
Resistant bacterial otitis High-dose amoxicillinclavulanate (80100 mg of amoxicillin/
kg per day orally) for 7 days, cefuroxime axetil (30 mg/kg
twice a day orally) for 7 days, or ceftriaxone (50 mg/kg per
day intramuscularly) for 3 days
*For children who are allergic to penicillin, preferred alternatives include cefuroxime axetil or an-other
second-generation cephalosporin (other than cefaclor, which may cause a serum-sicknesslike reaction),
azithromycin, or ceftriaxone (50 mg per kilogram once).
The delayed antibiotic-prescribing strategy is as follows: initiate treatment with full-dose ac-
etaminophen; provide a prescription for amoxicillin to be used only if otalgia or fever persists or if there is
no clinical improvement after 48 to 72 hours; advise the patients parents that antibiotics do not work very
well against otitis and have virtually no effect during the first 24 hours; explain the disadvantages of
antibiotics to patients parents they may have side effects (e.g., diarrhea and rash); and select for
resistant bacteria.15
In the absence of data on the efficacy of antibiotics for of diagnosis. One strategy to minimize unnecessary
resistant bacterial otitis, one expert panel recommend- prescribing of antibiotics is to delay treatment for 48 to
ed high-dose amoxicillinclavulanate, cefuroxime ax- 72 hours after the diagnosis to determine whether there
etil, or intramuscular ceftriaxone for three days.21 Tym- is spontaneous clinical improvement.15,23 This
panocentesis may help guide therapy. approach is used in the Netherlands: children, partic-
ularly those younger than two years of age, are closely
Delayed Antibiotic Therapy
monitored, and a seven-day course of antimicrobial
The small percentage of children who will benefit therapy is begun only when there is no improvement in
from an antibiotic are not easily identified at the time symptoms within one to two days in children
N Engl J Med, Vol. 347, No. 15 October 10, 2002 www.nejm.org 1171