Principles of Judicious Use of Antimicrobial Agents for Pediatric Upper

Respiratory Tract Infections

Scott F. Dowell, S. Michael Marcy, William R. Phillips, Michael A. Gerber and

Benjamin Schwartz

Pediatrics 1998;101;163-165

DOI: 10.1542/peds.101.1.S1.163

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The online version of this article, along with updated information and services, is
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http://www.pediatrics.org/cgi/content/full/101/1/S1/163

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

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overall, was helpful at day 5 in a subgroup of pa
tients with isolation of Streptococcus pneumoniae,
Moraxella catarrhalis, or Haemophilus influenzae on a
nasal swab.13 Given the modest benefit of antimicro
bial agents even in these subgroups and the lack of
benefit in most other studies (Table), antimicrobial
agents are not indicated for treatment of viral rhino-
sinusitis.
The agents causing the common cold identified
most commonly are rhinoviruses and coronaviruses,
which together account for up to 60% of infec
tions.2,14,15 Because these viruses are difficult to iden
tify, they also may cause a substantial proportion of
colds of unknown etiology. The etiologic agents of
the common cold vary with host, age, and time of
year. Each year in temperate climates, there are se
quential outbreaks caused by different viruses, such
as respiratory syncytial virus; influenza virus; coro
navirus; rhinovirus; and parainfluenza 1, 2, and 3
viruses, interspersed with endemic infections caused
by others, such as respiratory adenovirus. Occasion
ally, clinical findings may suggest a specific viral
agent; some respiratory adenovirus infections (such
as serotypes 3, 4, and 7) may present with pharyn
gitis and conjunctivitis, parainfluenza type 1 with
croup, and influenza with prominent constitutional
symptoms. More often, however, symptoms will be
nonspecific and not characteristic of a specific agent.
The signs and symptoms associated with the com
mon cold also may precede or accompany focal in
fections that are caused by bacteria. These infections,
which include otitis media and bacterial sinusitis,
should be diagnosed only when specific criteria are
fulfilled.16 –18 Unless clear evidence for the presence of
a focal bacterial infection is present, the constellation
of signs and symptoms associated with the common
cold do not warrant treatment with antimicrobial
agents.
Although a large majority of physicians realize
that antimicrobial therapy will not hasten resolution
of a cold, antimicrobials are often prescribed in an
attempt to prevent bacterial complications. There are
data that indicate that this is not an effective strategy.
A recent metaanalysis of five randomized clinical
trials of the efficacy of antimicrobial treatment of
colds to prevent lower respiratory infections found
no evidence for a protective effect.19 Although some
studies suggest that intermittent antimicrobials be
gun at the onset of respiratory symptoms can help
prevent acute otitis media in children at highest risk
of recurrent disease,20,21 other studies do not.22 Fur
thermore, this approach is less effective than stan
dard continuous prophylaxis, used for some high-
risk children who meet stringent criteria,23 when the
two approaches are compared directly.24
Other treatments are commonly used to treat the
symptoms of the common cold, and although most
show no benefit compared with placebo, some studies
have shown efficacy for symptomatic treatments. For
example, a controlled trial in adults of an antihistamine
(clemastine fumarate) for treatment of experimental
rhinovirus colds showed significant reductions in
sneezing, rhinorrhea, and nasal secretions;25 the reduc
tion in symptoms may be larger than the marginal
benefit in symptoms demonstrated in certain sub
groups by some antimicrobial trials. Therefore, if
symptomatic relief is sought by patients, selected home
remedies or preparations designed to treat symptoms
may provide similar, although marginal, benefits with
out the risk of antimicrobial-resistant bacterial coloni
zation or infection.
Mucopurulent rhinitis (thick, opaque, or discol
ored nasal discharge) frequently accompanies the
common cold. It is not an indication for antimicrobial
treatment unless it persists without improvement
for >10 to 14 days.
Most episodes of viral rhinosinusitis follow a pre
dictable course. Unnecessary antimicrobial therapy
can be avoided by recognizing the signs and symp
toms that are part of the usual course of this disease
and thus are not suggestive of a secondary bacterial
infection. Viral rhinosinusitis begins with the inocu
lation of virus onto the nasal, oral, or conjunctival
mucosa, followed by infection of the local respiratory
epithelium. The initial symptoms, which are caused
both by cellular damage and by the inflammatory
response, include nasal stuffiness and throat irrita
tion. Within a few hours, sneezing and watery nasal
discharge may occur, often accompanied by systemic
complaints such as low-grade fever, malaise, head
ache, anorexia, and myalgias.26 Cough occurs in 60%
to 80% of viral rhinosinusitis15,27,28 and does not nec
essarily suggest a bacterial etiology. One to three
days after the onset of illness, nasal secretions typi
cally become thicker and more mucopurulent be
cause they contain desquamated epithelial cells,
polymorphonuclear cells, and bacteria that normally
colonize the upper respiratory tract.28 Physicians of
ten differentiate mucopurulent rhinitis from viral
rhinosinusitis; however, mucopurulent rhinitis is
more appropriately considered part of the natural
history of viral rhinosinusitis, not a distinct disease,
and not an indication for antimicrobial therapy.29,30
The duration of illness usually ranges from 2 to 7
days. Although patients are generally improved by
day 10, lingering symptoms, including cough (in up
to 31% of patients) and nasal discharge (35%), can
persist in children and adolescents for �2 weeks.28,31
With an average of six respiratory tract infections per
year, and more if children are in day care,2– 6 many
children will have sequential episodes of viral rhino-
sinusitis with little time for improvement between
episodes.
In 1984, Todd32 randomized 142 children with mu
copurulent nasopharyngitis into groups that re
ceived either antimicrobials (cephalexin), symptom
atic therapy, or placebo. Although bacteria often
were identified in nasal secretions, antimicrobial
treatment did not reduce the number of potentially
pathogenic organisms obtained from nasopharyn
geal cultures. Additionally, no differences in clinical
outcomes between antimicrobial and placebo-treated
groups were found at 5 to 6 days, based on both
physician and parent assessments. Of the children
treated with antimicrobials, 76% had continued nasal
discharge, compared with 63% of those treated with
placebo (P � .1); 7% had evidence of complications,
compared with 8% of those treated with placebo
SUPPLEMENT 183
cific upper respiratory tract infection (URI). The
acute illness typically is characterized by rhinorrhea,
sore throat, cough, and fever. Because of the diffi
culty in defining criteria for this illness, the precise
incidence of viral rhinosinusitis has been difficult to
estimate. Most children will suffer between 3 and 8
colds per year; however, 10% to 15% of children will
have at least 12 per year, particularly those attending
day care centers.2– 6 A review of Kentucky Medicaid
claims found that 60% of patients seen for the com
mon cold were given an antimicrobial prescription;
that article estimated the annual cost of antimicrobial
prescribing for the common cold in the United States
at $37.5 million.7 A recent survey in northern
Virginia found that 71% of family practitioners and
53% of pediatricians would prescribe antimicrobials
immediately for a 10-month-old infant with scant,
green, mucopurulent nasal secretions of 1 day’s du
ration.8
Rhinosinusitis and mucopurulent rhinitis are al
most always caused by viral infections, for which
antimicrobial use changes neither the course nor the
outcome. Antimicrobial use is not only unnecessary
but potentially harmful, because it increases the risk
of colonization with resistant organisms and,
thereby, heightens the chances that any subsequent
invasive infection will be unresponsive to standard
antimicrobial therapy.9
EVIDENCE SUPPORTING PRINCIPLES
Antimicrobial Agents Should Not Be Given for the
Common Cold
Controlled trials of antimicrobial treatment of the
common cold have consistently failed to show that
treatment changes the course or outcome (Table). For
example, a 1962 prospective, double-blind study of
781 children with colds demonstrated that 3.5% of
those treated with antimicrobial agents developed
purulent URI, compared with 2.6% of those treated
symptomatically (P � .5).10 A more recent study of
261 children randomly treated with penicillin, tetra
cycline, or placebo showed similar results: 4.6% of
the placebo group either did not improve or pre
sented with evidence of a complication (eg, pneumo
nia) by 8 days, compared with 4.6% of the antimicro
bial group (P � 1).11
Two studies in adults showed modest benefits in
those treated with antimicrobial agents and should
be considered in evaluating the potential for benefit
to children. The first, involving 212 adults with
coughs or colds randomized to treatment with doxy
cycline or placebo, showed a reduction in the pro
portion with rhinorrhea at day 5 that was no longer
apparent by day 10.12 More recently, a trial of treat
ment with amoxicillin/clavulanate versus placebo
among 314 adults with cold symptoms showed that
antimicrobial treatment, although not beneficial

TABLE. Controlled Trials Assessing the Efficacy of Antibiotic Treatment for URI
Study (Year) N Comparison Groups Outcome Conclusion
Cronk et al33 (1954) 2177 PCN G and/or symptomatic Required return outpatient No difference between
treatment visit(s) PCN G 26%, groups
symptomatic 20%
Hardy et al34 (1956) 217 Abx* or placebo Rate of all infectious No difference between abx
complications abx 15%, and placebo
placebo 15%
Townsend35 (1960) 845 Abx† or symptomatic Rate of all infectious No difference between abx
treatment complications abx 14%, and symptomatic
symptomatic 9%
Townsend10 (1962) 781 Abx† or symptomatic Rate of complications (eg., No difference between abx
treatment AOM) abx 3.5%, and symptomatic
symptomatic 2.6%
Lexomboon et al11 (1971) 261 PCN V or tetracycline or Not improved or complicated No difference between abx
placebo abx 5%, placebo 5% and placebo
Gordon et al36 (1974) 89 Abx‡ or placebo Improved symptoms or signs Abx do not change short-
data not provided in term course of URI
publication
Stott and West12 (1976) 212 Doxycycline or placebo Runny nose at day 5 Doxycycline beneficial at day
(adults only) doxycycline 14%, placebo 5, not by day 10
30%
Taylor et al37 (1977) 197 Amoxicillin, co-trimoxazole, At day 8, purulent rhinitis: Marginal benefit from abx
or placebo amoxicillin 6%,
cotrimoxazole 4%, placebo
15%; at day 8, normal
activity: amoxicillin 89%,
cotrimoxazole 95%, placebo
97%
Kaiser et al13 (1996) 314 Coamoxiclav or placebo At day 5, for patients with Antibiotics may be indicated
(adults, 61 with �cultures: for a subset of adult
�nasopharyngeal cultures) persistent/worse patients, with sinusitis
symptoms coamoxiclav
73%, placebo 96%;
Abbreviations: PCN indicates penicillin; abx, antibiotics; AOM, acute otitis media; coamoxiclav, amoxycillin/clavulanate.
* Three antibiotic groups: Gantrisin, Aureomycin, or penicillin.
† Four antibiotic groups: sulfonamides, tetracycline, penicillin, or chloramphenicol.
‡ Three antibiotic groups: ampicillin, penicillin, or erythromycin.

182 SUPPLEMENT
 tory illnesses in pediatric practice. N Engl J Med. 1962;266:683– 689
15. Gordon M, Lovell S, Dugdale AE. The value of antibiotics in minor
respiratory illness in children. Med J Aust. 1974;1:304 –306
16. Taylor B, Abbott GD, McKerr M, Fergusson DM. Amoxycillin and
cotrimoxazole in presumed viral respiratory infections of childhood:
placebo-controlled trial. Br Med J. 1977;2:552–554
17. Gadomski AM. Potential interventions for preventing pneumonia
among young children: lack of effect of antibiotic treatment for upper
respiratory infections. Pediatr Infect Dis J. 1993;12:115–120
18. Weissenbacher M, Carballal G, Avila M, et al. Etiologic and clinical
evaluation of acute lower respiratory tract infections in young Argen
tinian children: an overview. Rev Infect Dis. 1990;12:S889 –S898
19. Suwanjutha S, Chantarojanasiri T, Watthana-kasetr S, et al. A study of
nonbacterial agents of acute lower respiratory tract infection in Thai
children. Rev Infect Dis. 1990;12:S923–S928
20. Falck G, Gnarpe J, Gnarpe H. Prevalence of Chlamydia pneumoniae in
healthy children and in children with respiratory tract infections. Pediatr
Infect Dis J. 1997;16(6):549 –554
21. Horn MEC, Reed SE, Taylor P. Role of viruses and bacteria in acute
wheezy bronchitis in childhood: a study of sputum. Arch Dis Child.
1979;54:587–592
22. Gehanno P, Lenoir G, Barry B, Bons J, Boucot I, Berche P. Evaluation of
nasopharyngeal cultures for bacteriologic assessment of acute otitis
media in children. Pediatr Infect Dis J. 1996;15:329 –332
23. Todd JK. Bacteriology and clinical relevance of nasopharyngeal and
oropharyngeal cultures. Pediatr Infect Dis J. 1984;3:159 –163
24. Wald E, Milmoe G, Bowen A, Ledesma-Medina J, Salamon N, Bluestone
C. Acute maxillary sinusitis in children. N Engl J Med. 1981;304:749 –754
25. Mimica I, Donoso E, Howard JE, et al. Lung puncture in the etiological
diagnosis of pneumonia. Am J Dis Child. 1971;122:278 –282
26. Hall WJ, Hall CB, Speers DM. Respiratory syncytial virus infection in
adults. Ann Intern Med. 1978;88:203–205
27. Cate TR, Couch RB, Fleet WF, Griffith WR, Gerone PJ, Knight V.
Production of tracheobronchitis in volunteers with rhinovirus in a
small-particle aerosol. Am J Epidemiol. 1965;81:95–105
28. Monto AS, Napier JA, Metzner HL. The Tecumseh study of respiratory
illness. I. Plan of study and observations on syndromes of acute respi
ratory disease. Am J Epidemiol. 1971;94:269 –279
The Common Cold—Principles of Judicious Use of Antimicrobial Agents
Nancy Rosenstein, MD*; William R. Phillips, MD, MPH§; Michael A. Gerber, MD�; S. Michael Marcy, MD‡;
Benjamin Schwartz, MD*; and Scott F. Dowell, MD*
ABSTRACT. Most children will suffer between 3 and 8
colds per year, and over half of patients seen for the com
mon cold are given an antimicrobial prescription. Unnec
essary antimicrobial therapy can be avoided by recognizing
the signs and symptoms that are part of the usual course of
these diseases. Controlled trials of antimicrobial treatment
of the common cold are reviewed. These trials consistently
fail to show that treatment changes the course or outcome.
Furthermore, antimicrobial therapy for patients with viral
rhinosinusitis is not an effective way to prevent bacterial
complications. Mucopurulent rhinitis (thick, opaque, or
discolored nasal discharge) frequently accompanies the
From the *Childhood and Respiratory Diseases Branch, Division of Bacterial
nasal discharge) frequently accompanies the com
and Mycotic Diseases, National Center for Infectious Diseases, Centers for
Disease Control and Prevention, Public Health Service, US Department of
Health and Human Services, Atlanta, Georgia; ‡Kaiser Permanente, Pan
orama City, California; §Northwest Family Medicine, Seattle, Washington;
and �Connecticut Children’s Medical Center, Hartford, Connecticut.
BACKGROUND AND JUSTIFICATION
Received for publication Aug 8, 1997; accepted Sep 11, 1997.
Reprint requests to (S.F.D.) Centers for Disease Control and Prevention,
Mailstop C-23, 1600 Clifton Rd, NE, Atlanta, GA 30333.
PEDIATRICS (ISSN 0031 4005). Copyright © 1998 by the American Acad
viral rhinosinusitis is used in this paper as a
emy of Pediatrics.
synonym for the common cold syndrome or nonspe-
29. Gwaltney JM, Hendley JO, Simon G. Rhinovirus infections in an indus
trial population. II. Characteristics of illness and antibody response.
JAMA. 1967;202:494 –500
30. Cloutier MM, Loughlin GM. Chronic cough in children: a manifestation
of airway hyperreactivity. Pediatrics. 1981;67:6 –12
31. Konig P. Hidden asthma in childhood. Am J Dis Child. 1981;135:
1053–1055
32. Corrao WM, Sidney MD, Braman SS, Irwin RS. Chronic cough as the
sole presenting manifestation of bronchial asthma. N Engl J Med. 1979;
300:633– 637
33. Morgan WJ, Taussig LM. The chronic bronchitis complex in children.
Pediatr Clin North Am. 1984;31:851– 864
34. Gwaltney JM, Hendley JO, Simon G, Jordan WS. Rhinovirus infections
in an industrial population. JAMA. 1967;202:158 –164
35. Mink CM, Cherry JD, Christenson P, et al. A search for Bordetella
pertussis infection in university students. Clin Infect Dis. 1992;14:464 – 471
36. American Academy of Pediatrics. Pertussis. In: Peter G, ed. 1997 Red
Book. Report of the Committee on Infectious Diseases. 24th ed. Elk Grove
Village, IL: American Academy of Pediatrics; 1997:394 –397
37. Denny FW, Clyde WA, Glezen WP. Mycoplasma pneumoniae disease
clinical spectrum, pathophysiology, epidemiology and control. J Infect
Dis. 1971;123:74 –92
38. Foy HM, Cooney MK, Maletzky AJ, Grayston JT. Incidence and etiology
of pneumonia, croup and bronchiolitis in preschool children belonging
to a prepaid medical care group over a four-year period. Am J Epidemiol.
1973;97:80 –92
39. Foy JH. Infections caused by Mycoplasma pneumoniae and possible car
rier state in different populations of patients. Clin Infect Dis. 1996;
17(suppl 1):S37–S46
40. Stevens D, Swift PGF, Johnston PGB, Kearney PJ, Corner BD, Burman D.
Mycoplasma pneumoniae infections in children. Arch Dis Child. 1978;53:38 –42
41. Broughton RA. Infections due to Mycoplasma pneumoniae in childhood.
Pediatr Infect Dis J. 1986;5:71– 85
42. Nohynek H, Eskola J, Kleemola M, Jalonen E, Saiddu P, Leinonen M.
Bacterial antibody assays in the diagnosis of acute lower respiratory
tract infection in children. Pediatr Infect Dis J. 1996;14:478 – 484
43. Moss RB. Cystic fibrosis: pathogenesis, pulmonary infection, and treat
ment. Clin Infect Dis J. 1995;21:839 – 851
common cold and is part of the natural course of viral
rhinosinusitis. It is not an indication for antimicrobial
treatment unless it persists without improvement for >10
to 14 days. Pediatrics 1998;101:181–184; common cold, up
per respiratory tract infection, mucopurulent rhinitis, di
agnosis, antimicrobial therapy.
ABBREVIATION. URI, upper respiratory tract infection.
PRINCIPLES
1. Antimicrobial agents should not be given for the
common cold.
2. Mucopurulent rhinitis (thick, opaque, or discolored
mon cold. It is not an indication for antimicrobial
treatment unless it persists for �10 to 14 days.
R
ecent evidence suggests that the common cold
usually includes sinus disease.1 Therefore,
SUPPLEMENT 181
 tory illnesses in pediatric practice. N Engl J Med. 1962;266:683– 689
15. Gordon M, Lovell S, Dugdale AE. The value of antibiotics in minor
respiratory illness in children. Med J Aust. 1974;1:304 –306
16. Taylor B, Abbott GD, McKerr M, Fergusson DM. Amoxycillin and
cotrimoxazole in presumed viral respiratory infections of childhood:
placebo-controlled trial. Br Med J. 1977;2:552–554
17. Gadomski AM. Potential interventions for preventing pneumonia
among young children: lack of effect of antibiotic treatment for upper
respiratory infections. Pediatr Infect Dis J. 1993;12:115–120
18. Weissenbacher M, Carballal G, Avila M, et al. Etiologic and clinical
evaluation of acute lower respiratory tract infections in young Argen
tinian children: an overview. Rev Infect Dis. 1990;12:S889 –S898
19. Suwanjutha S, Chantarojanasiri T, Watthana-kasetr S, et al. A study of
nonbacterial agents of acute lower respiratory tract infection in Thai
children. Rev Infect Dis. 1990;12:S923–S928
20. Falck G, Gnarpe J, Gnarpe H. Prevalence of Chlamydia pneumoniae in
healthy children and in children with respiratory tract infections. Pediatr
Infect Dis J. 1997;16(6):549 –554
21. Horn MEC, Reed SE, Taylor P. Role of viruses and bacteria in acute
wheezy bronchitis in childhood: a study of sputum. Arch Dis Child.
1979;54:587–592
22. Gehanno P, Lenoir G, Barry B, Bons J, Boucot I, Berche P. Evaluation of
nasopharyngeal cultures for bacteriologic assessment of acute otitis
media in children. Pediatr Infect Dis J. 1996;15:329 –332
23. Todd JK. Bacteriology and clinical relevance of nasopharyngeal and
oropharyngeal cultures. Pediatr Infect Dis J. 1984;3:159 –163
24. Wald E, Milmoe G, Bowen A, Ledesma-Medina J, Salamon N, Bluestone
C. Acute maxillary sinusitis in children. N Engl J Med. 1981;304:749 –754
25. Mimica I, Donoso E, Howard JE, et al. Lung puncture in the etiological
diagnosis of pneumonia. Am J Dis Child. 1971;122:278 –282
26. Hall WJ, Hall CB, Speers DM. Respiratory syncytial virus infection in
adults. Ann Intern Med. 1978;88:203–205
27. Cate TR, Couch RB, Fleet WF, Griffith WR, Gerone PJ, Knight V.
Production of tracheobronchitis in volunteers with rhinovirus in a
small-particle aerosol. Am J Epidemiol. 1965;81:95–105
28. Monto AS, Napier JA, Metzner HL. The Tecumseh study of respiratory
illness. I. Plan of study and observations on syndromes of acute respi
ratory disease. Am J Epidemiol. 1971;94:269 –279
The Common Cold—Principles of Judicious Use of Antimicrobial Agents
Nancy Rosenstein, MD*; William R. Phillips, MD, MPH§; Michael A. Gerber, MD�; S. Michael Marcy, MD‡;
Benjamin Schwartz, MD*; and Scott F. Dowell, MD*
ABSTRACT. Most children will suffer between 3 and 8
colds per year, and over half of patients seen for the com
mon cold are given an antimicrobial prescription. Unnec
essary antimicrobial therapy can be avoided by recognizing
the signs and symptoms that are part of the usual course of
these diseases. Controlled trials of antimicrobial treatment
of the common cold are reviewed. These trials consistently
fail to show that treatment changes the course or outcome.
Furthermore, antimicrobial therapy for patients with viral
rhinosinusitis is not an effective way to prevent bacterial
complications. Mucopurulent rhinitis (thick, opaque, or
discolored nasal discharge) frequently accompanies the
From the *Childhood and Respiratory Diseases Branch, Division of Bacterial
nasal discharge) frequently accompanies the com
and Mycotic Diseases, National Center for Infectious Diseases, Centers for
Disease Control and Prevention, Public Health Service, US Department of
Health and Human Services, Atlanta, Georgia; ‡Kaiser Permanente, Pan
orama City, California; §Northwest Family Medicine, Seattle, Washington;
and �Connecticut Children’s Medical Center, Hartford, Connecticut.
BACKGROUND AND JUSTIFICATION
Received for publication Aug 8, 1997; accepted Sep 11, 1997.
Reprint requests to (S.F.D.) Centers for Disease Control and Prevention,
Mailstop C-23, 1600 Clifton Rd, NE, Atlanta, GA 30333.
PEDIATRICS (ISSN 0031 4005). Copyright © 1998 by the American Acad
viral rhinosinusitis is used in this paper as a
emy of Pediatrics.
synonym for the common cold syndrome or nonspe-
29. Gwaltney JM, Hendley JO, Simon G. Rhinovirus infections in an indus
trial population. II. Characteristics of illness and antibody response.
JAMA. 1967;202:494 –500
30. Cloutier MM, Loughlin GM. Chronic cough in children: a manifestation
of airway hyperreactivity. Pediatrics. 1981;67:6 –12
31. Konig P. Hidden asthma in childhood. Am J Dis Child. 1981;135:
1053–1055
32. Corrao WM, Sidney MD, Braman SS, Irwin RS. Chronic cough as the
sole presenting manifestation of bronchial asthma. N Engl J Med. 1979;
300:633– 637
33. Morgan WJ, Taussig LM. The chronic bronchitis complex in children.
Pediatr Clin North Am. 1984;31:851– 864
34. Gwaltney JM, Hendley JO, Simon G, Jordan WS. Rhinovirus infections
in an industrial population. JAMA. 1967;202:158 –164
35. Mink CM, Cherry JD, Christenson P, et al. A search for Bordetella
pertussis infection in university students. Clin Infect Dis. 1992;14:464 – 471
36. American Academy of Pediatrics. Pertussis. In: Peter G, ed. 1997 Red
Book. Report of the Committee on Infectious Diseases. 24th ed. Elk Grove
Village, IL: American Academy of Pediatrics; 1997:394 –397
37. Denny FW, Clyde WA, Glezen WP. Mycoplasma pneumoniae disease
clinical spectrum, pathophysiology, epidemiology and control. J Infect
Dis. 1971;123:74 –92
38. Foy HM, Cooney MK, Maletzky AJ, Grayston JT. Incidence and etiology
of pneumonia, croup and bronchiolitis in preschool children belonging
to a prepaid medical care group over a four-year period. Am J Epidemiol.
1973;97:80 –92
39. Foy JH. Infections caused by Mycoplasma pneumoniae and possible car
rier state in different populations of patients. Clin Infect Dis. 1996;
17(suppl 1):S37–S46
40. Stevens D, Swift PGF, Johnston PGB, Kearney PJ, Corner BD, Burman D.
Mycoplasma pneumoniae infections in children. Arch Dis Child. 1978;53:38 –42
41. Broughton RA. Infections due to Mycoplasma pneumoniae in childhood.
Pediatr Infect Dis J. 1986;5:71– 85
42. Nohynek H, Eskola J, Kleemola M, Jalonen E, Saiddu P, Leinonen M.
Bacterial antibody assays in the diagnosis of acute lower respiratory
tract infection in children. Pediatr Infect Dis J. 1996;14:478 – 484
43. Moss RB. Cystic fibrosis: pathogenesis, pulmonary infection, and treat
ment. Clin Infect Dis J. 1995;21:839 – 851
common cold and is part of the natural course of viral
rhinosinusitis. It is not an indication for antimicrobial
treatment unless it persists without improvement for >10
to 14 days. Pediatrics 1998;101:181–184; common cold, up
per respiratory tract infection, mucopurulent rhinitis, di
agnosis, antimicrobial therapy.
ABBREVIATION. URI, upper respiratory tract infection.
PRINCIPLES
1. Antimicrobial agents should not be given for the
common cold.
2. Mucopurulent rhinitis (thick, opaque, or discolored
mon cold. It is not an indication for antimicrobial
treatment unless it persists for �10 to 14 days.
R
ecent evidence suggests that the common cold
usually includes sinus disease.1 Therefore,
SUPPLEMENT 181
improvement in airway reactivity.30 –33 Because bron
chospasm is commonly triggered by an acute viral
respiratory infection, these children require treat
ment for relief of bronchospasm, not antibiotics.
Careful studies of experimentally induced and cul
ture-confirmed rhinovirus colds in adults have doc
umented that cough persists after fever, myalgia,
sneezing, and sore throat have resolved.27,29,34 In fact,
20% of subjects continue to cough �14 days after
onset of symptoms.29 A clear understanding that pro
longed cough is an expected part of uncomplicated
viral upper respiratory tract infection and does not
itself indicate a bacterial infection of the bronchi or
the sinuses should help practitioners and patients
avoid a large burden of unnecessary antibiotic use.
Prolonged cough caused by other specific patho
gens may benefit from antimicrobial treatment and
should be considered in the differential diagnosis of
prolonged cough. Pertussis classically causes parox
ysms of cough followed by a characteristic inspira
tory whoop. Particularly among older children and
adults, pertussis also can present with a prolonged
cough and no whoop. In a study of 130 university
students with cough for �6 days, 26% were found to
have culture or serology evidence of a recent Borde
tella pertussis infection.35 Treatment with erythromy
cin, if started early in the course of disease, may
decrease the duration of symptoms. However, if
started later in disease, treatment with erythromycin
may only diminish communicability of B pertussis,
but is of no value in hastening resolution of the
cough.36 A diagnosis of pertussis can be confirmed
by culture of the organism or antigen detection from
NP secretions in the acute phase or serologic diag
nosis in the later phases of the illness.
Although M pneumoniae infections may occur in
young children, they are more likely to be mild,
nonpneumonic infections than those in school chil
dren and adolescents, which may cause pneumonia
and prolonged respiratory illness with cough.37–39
Specific antimicrobial therapy may be of benefit in
decreasing communicability and shortening the du
ration of illness, although the effect on the latter is
small.40,41 There are no specific or pathognomonic
signs of cough caused by M pneumoniae infection.
Therefore, treatment should not be given unless the
cough illness is prolonged or pneumonia is docu
mented. Laboratory confirmation of the diagnosis is
usually made by acute- and convalescent-phase se
rologic testing.42 When treatment is elected, a mac
rolide antimicrobial agent or tetracycline for children
�8 years of age should be used.
Diagnosis and management of cough illness/bron
chitis in children with underlying chronic pulmonary
disease must take into consideration differences in ep
idemiology, natural history, and pathogenesis. Chil
dren with cystic fibrosis may benefit from antimicrobial
therapy directed at Pseudomonas aeruginosa, Staphylococ
cus aureus, or Haemophilus influenzae during episodes
characterized by cough, increased secretions, rales,
rhonchi, and fever.43 Similarly, children with other un
derlying severe chronic lung diseases (eg, bronchopul
monary dysplasia, lung hypoplasia, ciliary dyskinesia,
chronic aspiration) may be more likely to benefit from
180 SUPPLEMENT
antibiotic treatment because of increased likelihood of
bacterial colonization, impaired pulmonary clearance
mechanisms, or immune compromise. Treatment must
be tailored for each child; general principles of judi
cious antimicrobial use are particularly appropriate for
these children to decrease the adverse effects from mul
tiple courses of antibiotics and resultant colonization
with antibiotic-resistant organisms.
Children with markedly prolonged cough (4 to 8
weeks) should be investigated for possibly treatable
causes, including reactive airway disease, tuberculo
sis, foreign body aspiration, pertussis, cystic fibrosis,
or sinusitis. If possible, empiric antimicrobial ther
apy should be avoided in the initial management of
a prolonged cough; rather, a specific diagnosis
should be sought.
The practice of restricting antibiotic use to a small
subset of prolonged cough illnesses is supported by the
medical literature. Standard pamphlets or letters ex
plaining the nature of the illness may facilitate the
return to day care or school of a child with a viral
respiratory infection or allergy-induced cough who is
otherwise well. The cost of a follow-up visit for those
few children whose illness is not improving over time
should be balanced against the high likelihood of spon
taneous resolution of the coughing illness without an
tibiotic therapy and the risk to the child and the com
munity of unnecessary antibiotic use.
ACKNOWLEDGMENTS
We authors thank Drs Leah Raye Mabry and Doug Long and
members of the Committee on Infectious Diseases of the American
Academy of Pediatrics, for their careful reviews of this paper.
REFERENCES
1. Chapman RS, Henderson FW, Clyde WA, Collier AM, Denny FW. The
epidemiology of tracheobronchitis in pediatric practice. Am J Epidemiol.
1981;114:786 –797
2. Monto AS, Cavallaro JJ. The Tecumseh study of respiratory illness. II.
Patterns of occurrence of infection with respiratory pathogens,
1965–1969. Am J Epidemiol. 1971;94:280 –289
3. Glezen WP, Denny FW. Epidemiology of acute lower respiratory dis
ease in children. N Engl J Med. 1973;288:498 –505
4. Vinson DC, Lutz LJ. The effect of parental expectations on treatment of
children with a cough: a report from ASPN. J Fam Pract. 1993;37:23–27
5. Orr PH, Scherer K, Macdonald A, Moffatt MEK. Randomized placebo-
controlled trials of antibiotics for acute bronchitis: acritical review of the
literature. J Fam Pract. 1993;36:507–512
6. Dunlay J, Reinhardt R, Donn Roi L. A placebo-controlled, double-blind
trial of erythromycin in adults with acute bronchitis. J Fam Pract. 1987;
25:137–141
7. Franks P, Gleiner JA. The treatment of acute bronchitis with tri
methoprim and sulfamethoxazole. J Fam Pract. 1984;19:185–190
8. Verheij TJM, Hermans J, Mulder JD. Effects of doxycycline in patients
with acute cough and purulent sputum: a double blind placebo con
trolled trial. Br J Gen Pract. 1994;44:400 – 404
9. Stott NCH, West RR. Randomised controlled trial of antibiotics in
patients with cough and purulent sputum. Br Med J. 1976;2:556 –559
10. Williamson HA. A randomized, controlled trial of doxycycline in the
treatment of acute bronchitis. J Fam Pract. 1984;19:481– 486
11. Howie JGR, Clark GA. Double-blind trial of early demethylchlortetra
cycline in minor respiratory illness in general practice. Lancet. 1970;2:
1099 –1102
12. Brickfield FX, Carter WH, Johnson RE. Erythromycin in the treat
ment of acute bronchitis in a community practice. J Fam Pract.
1986;23:119 –122
13. Townsend EH. Chemoprophylaxis during respiratory infections in a
private pediatric practice. Am J Dis Child. 1960;99:566 –573
14. Townsend EH, Radebaugh JF. Prevention of complications of respira
lished in the English language, peer-reviewed medical
literature. A metaanalysis that included six of these
studies concluded that there is no evidence to support
the use of antibiotic treatment for acute bronchitis.5
Three trials that used erythromycin, doxycycline, or
trimethoprim/sulfamethoxasole demonstrated mini
mal improvement in duration of cough and time lost
from work in the group treated with antibiotics.6 – 8 The
remaining four trials, including the two that the au
thors concluded best fulfilled criteria for methodologic
soundness, showed no difference in outcomes between
those who received placebo and those treated with
erythromycin, doxycycline, or tetracycline.9 –12
There are no randomized, placebo-controlled anti
biotic trials of children with cough illness/bronchitis
strictly defined by sputum production; however,
several pediatric studies have evaluated the use of
antibiotics for cough illnesses, which in common
practice are called bronchitis and are treated with
antibiotics.13–16 None of these studies showed any
benefit of antibiotic use for the cough.
Although most practitioners recognize that the
majority of cough illness results from viral infections,
some believe that lower respiratory bacterial super
infections might be averted by prophylactic use of
antimicrobial agents. At least nine trials have evalu
ated the role of antibiotic treatment for preventing
bacterial complications of viral respiratory illnesses.
A metaanalysis of these trials concluded that antibi
otics did not prevent or decrease the severity of
bacterial complications subsequent to viral respira
tory tract infections.17
The lack of benefit from antimicrobial therapy is
consistent with community- and hospital-based
studies in the United States and other areas of the
world that implicate nonbacterial organisms as the
etiologic agents of cough illness/bronchitis. These
studies demonstrate that viral pathogens such as
parainfluenza virus, respiratory syncytial virus, and
influenza virus account for the majority of agents
identified among children with cough illness/bron
chitis.1,2,18,19 Among children �5 years, Mycoplasma
pneumoniae was also recognized to cause cough ill
ness/bronchitis.1 Recently, Chlamydia pneumoniae has
also been isolated from children with nonspecific
cough illness.20 Taken together, there is ample evi
dence that cough illness/bronchitis in children is
primarily caused by viral pathogens or, in the case of
older children, sometimes by M pneumoniae or C
pneumoniae. There is little if any microbiologic evi
dence for an important role of other pathogenic bac
teria in the etiology of cough illness/bronchitis.
Unequivocally establishing the etiology of cough
illness/bronchitis is difficult, because obtaining se
cretions directly from the bronchi of children with
this syndrome is an invasive procedure and seldom
done. Neither the character nor the culture results of
surrogate specimens such as sputum (defined by the
presence of fewer than 10 epithelial cells per high-
power field) or nasopharyngeal (NP) secretions is
sufficiently predictive of a bacterial infection of the
bronchi to be of use in defining the need for antimi
crobial therapy. Sputum, comprising epithelial cells,
polymorphonuclear lymphocytes, and noncellular
elements, is a nonspecific response to airway inflam
mation, produced in response to both viral and bac
terial infections as well as to noninfectious processes.
In a study of 72 acute episodes of wheezy bronchitis
among 22 children 5 to 15 years of age, only 17% of
sputum samples contained a potentially pathogenic
bacterium, and in half of these samples, a viral
pathogen also was isolated.21 Leukocytes were found
in 82% of virus-positive sputum specimens and in
85% of bacteria-positive specimens. Thus, in the ab
sence of physical signs of pneumonia, neither the
production of sputum nor the character of sputum is
predictive of a bacterial etiology for cough. The pres
ence of bacteria in a culture of NP secretions also
should not be used as an indication that cough may
be caused by a bacterial pathogen. Studies have eval
uated the use of NP cultures to predict the causative
organism of other upper and lower respiratory tract
infections, such as otitis media, sinusitis, and pneu
monia, for which there are accepted standard meth
ods for obtaining specimens directly from the site of
infection.22–25 Simultaneous cultures of the nasophar
ynx and middle ear fluid,22 maxillary sinus fluid,24 or
percutaneous lung aspiration specimens25 demon
strated that NP cultures were poor predictors of the
true bacterial pathogens. By analogy, it can be sur
mised that NP cultures are not likely to be useful in
predicting the presence of bacteria in the bronchi.
Finally, it should be noted that the mere presence of
bacteria at the level of the bronchi, even if there were
practical means to collect such specimens, may not
reflect true infection of the bronchial mucosa.
Some practitioners use the presence of fever in
conjunction with cough to diagnose bronchitis and
prescribe antibiotic treatment.4 However, fever is an
expected component of cough illness/bronchitis and
does not indicate that cough is related to a bacterial
infection or that any benefit would be derived from
antimicrobial therapy. In studies of experimentally
and naturally induced viral respiratory infections,
fever was found to be a common sign, especially in
the first 2 days of illness, which resolved over the
ensuing few days.26 –29
Antimicrobial Treatment for Prolonged Cough
(>10 Days) Occasionally May Be Indicated
Pertussis should be treated according to estab
lished recommendations. Mycoplasma pneumoniae in
fection may cause pneumonia and prolonged cough
(usually in children �5 years of age); a macrolide
agent (or tetracycline for children �8 years of age)
may be used for treatment. Children with underlying
chronic pulmonary disease (not including asthma)
occasionally may benefit from antimicrobial therapy
for acute exacerbations.
The majority of prolonged cough illnesses are al
lergic, postinfectious, or viral in nature and do not
require antibiotic therapy. Reactive airway disease
has been recognized recently as one of the most
common causes of recurrent or prolonged cough
among children.30 These children may have minimal
or no appreciable wheezing on physical examination
but may respond dramatically to bronchodilator
therapy, with resolution of cough and documented
SUPPLEMENT 179
 Cough Illness/Bronchitis—Principles of Judicious Use of
Antimicrobial Agents
Katherine L. O’Brien, MD*; Scott F. Dowell, MD, MPH*; Benjamin Schwartz, MD*; S. Michael Marcy, MD‡;
William R. Phillips, MD, MPH§; and Michael A. Gerber, MD�
ABSTRACT. Millions of courses of antibiotics are pre
scribed for children with acute cough illness each year,
despite evidence from randomized, placebo-controlled
trials that such treatment is not effective. Evidence that
children with cough for <10 days should not be treated
with antimicrobial agents is presented. Older children
with prolonged cough or those with underlying lung
disease may benefit from antimicrobial treatment di
rected specifically at B pertussis, M pneumoniae, C pneu
moniae, P aeruginosa, or other specific infections. None
of the routinely prescribed cephalosporin or amino pen
icillin antimicrobials would be effective for these organ
isms. Noninfectious diagnosis should be sought in chil
dren with markedly prolonged cough. Pediatrics 1998;
101:178 –181; bronchitis, cough, diagnosis, antimicrobial
therapy, antimicrobial resistance, pediatrics.
ABBREVIATION. NP, nasopharyngeal.
PRINCIPLES
1. Regardless of duration, nonspecific cough illness/
bronchitis in children rarely warrants antimicro
bial treatment.
2. Antimicrobial treatment for prolonged cough
(�10 days) may be indicated occasionally. Pertus
sis should be treated according to established rec
ommendations. Mycoplasma pneumoniae infection
may cause pneumonia and prolonged cough (usu
ally in children �5 years of age); a macrolide
agent (or tetracycline for children �8 years of age)
may be used for treatment. Children with under
lying chronic pulmonary disease (not including
asthma) may benefit occasionally from antimicro
bial therapy for acute exacerbations.
BACKGROUND AND JUSTIFICATION
B
ronchitis is technically defined as inflammation
of the bronchial respiratory mucosa, resulting in
productive cough. The clinical definition of bron
chitis in children is not well established, but most cli
nicians who make the diagnosis do so for a child with
cough, with or without fever or sputum production.
From the *Childhood and Respiratory Diseases Branch, DBMD, National
Center for Infectious Diseases, Centers for Disease Control and Prevention,
Atlanta, Georgia; ‡Kaiser Permanente, Panorama City, California; §North
EVIDENCE SUPPORTING PRINCIPLES
west Family Medicine, Seattle, Washington; and �Connecticut Children’s
Medical Center, Hartford, Connecticut.
Regardless of Duration, Nonspecific Cough
Received for publication Aug 8, 1997; accepted Sep 11, 1997.
Illness/Bronchitis in Children Rarely Warrants
Reprint requests to (S.F.D.) Centers for Disease Control and Prevention,
Antimicrobial Treatment
Mailstop C-23, 1600 Clifton Rd, NE, Atlanta, GA 30333.
PEDIATRICS (ISSN 0031 4005). Copyright © 1998 by the American Adcad
Seven randomized, placebo-controlled antibiotic tri
emy of Pediartics.
als for bronchitis among adult patients have been pub
178 SUPPLEMENT
Although the term bronchitis does not imply any spe
cific etiology and studies demonstrate that this self-
resolving illness is most commonly caused by viral
pathogens,1–3 in practice, a diagnosis of bronchitis often
results in a prescription for an antimicrobial agent,
reflecting the belief that bacteria cause this illness. Mil
lions of antibiotic courses are prescribed each year for
children diagnosed with bronchitis. In a study of 1398
outpatient visits of children �14 years old with a chief
complaint of cough, bronchitis was diagnosed in 33%
of cases, and 88% of these children were prescribed an
antimicrobial.4
Because the pathologic definition of bronchitis as
inflammation of the bronchi does not reflect the
term’s clinical usage, imply the need for antimicro
bial therapy, or imply a specific etiology, the diag
nosis and management of cough illness in children
will be reviewed here using the term cough illness/
bronchitis. This term excludes more specific diag
noses such as pneumonia, bronchiolitis, and asthma.
A variety of terms are used in the literature to
describe conditions marked by cough, including
bronchitis, wheezy bronchitis, tracheobronchitis, and
asthmatic bronchitis. The lack of consensus regard
ing nomenclature and clinical definitions of cough
illnesses leads to difficulty comparing patient popu
lations and results from studies of cough illness/
bronchitis. The lack of a standardized case definition,
the difficulty of obtaining appropriate specimens for
viral and bacterial diagnostic tests, the high rate of
spontaneous resolution of illness, and the lack of
placebo-controlled treatment trials for pediatric
cough illness/bronchitis all undermine the establish
ment of a firm consensus on diagnosis and treat
ment. However, studies among adolescent and adult
patients, together with the few pediatric studies of
cough illness, provide important information about
the treatment and natural history of cough illness/
bronchitis that can be applied to children. Despite
the need for additional research, information is suf
ficient to provide principles that can be used to limit
unnecessary use of antimicrobial agents for treat
ment of this condition.
treatment trial of children with acute sinusitis (di
agnosed by symptoms of 10 to 30 days and radio
graphic abnormalities) demonstrated that for 50%
of the children in the placebo group, symptoms
improved by day 3 of treatment and for 60% by
day 10 of treatment, compared with 85% and 77%,
respectively, of children treated with either amoxi
cillin or amoxicillin-clavulanic acid.9 Similar re
sults have been observed in the three placebo-
controlled treatment trials conducted among
adults.10,11,31 In addition, despite �-lactamase pro
duction by some isolates of H influenzae and almost
all M catarrhalis, therapy with amoxicillin still is
successful for the initial treatment of acute uncom
plicated sinusitis in most children.8
For recurrent infections or for patients who do
not demonstrate a clinical response in 48 to 72
hours, a �-lactamase-stable agent (eg, amoxicillin
clavulanic acid or �-lactamase-stable cephalospo
rins active against pneumococcus) or an agent ac
tive against penicillin-resistant pneumococci (eg,
clindamycin or high-dose amoxicillin) should be
considered.32 When children experience a recur
rence of symptoms, the practitioner must try to
distinguish clinical relapse from another episode
of viral URI, with or without a bacterial infection
of the paranasal sinuses.
The duration of antimicrobial therapy should be
limited to 7 days beyond the point of substantial
improvement or resolution of signs and symptoms;
this is usually a 10- to 14-day course of treatment.
There is no need for more prolonged therapy (ie, 3 to
4 weeks) unless improvement in signs and symp
toms is delayed. Although one study of abbreviated
courses of antibiotics (ie, �10 days) has been con
ducted among adults,33 there have been no system
atic studies in children.
ACKNOWLEDGMENTS
We thank Drs Ellen R. Wald, Leah Raye Mabry, and Doug Long
and members of the Committee on Infectious Diseases of the
American Academy of Pediatrics for their careful review of this
paper.
REFERENCES
1. McCaig LF, Hughes JM. Trends in antimicrobial drug prescribing
among office-based physicians in the United States. JAMA. 1995;273:
214 –219
2. Monto AS, Ullman BM. Acute respiratory illness in an American com
munity. JAMA. 1974;227:164 –169
3. Badger GF, Dingle JH, Feller AE, Hodges RG, Jordan WS, Rammelkamp
CH. A study of illness in a group of Cleveland families. Am J Hyg.
1953;58:31– 40
4. Wald E, Guerra N, Byers C. Upper respiratory tract infections in young
children: duration of and frequency of complications. Pediatrics. 1991;
87:129 –133
5. Gwaltney J, Phillips C, Miller R, Riker D. Computed tomographic study
of the common cold. N Engl J Med. 1994;330:25–30
6. Gwaltney JM. Acute community-acquired sinusitis. Clin Infect Dis. 1996;
23:1209 –1225
7. Wald ER. Sinusitis in children. Pediatr Infect Dis J. 1988;7:S150 –S153
8. Giebink GS. Childhood sinusitis: pathophysiology, diagnosis and treat
ment. Pediatr Infect Dis J. 1994;13:S55–S65
9. Wald E, Chiponis D, Ledesma-Medina J. Comparative effectiveness of
amoxicillin and amoxicillin-clavulanate potassium in acute paranasal
sinus infections in children: a double-blind, placebo-controlled trial.
Pediatrics. 1986;77:795– 800
10. Lindbaek M, Hjortdahl P, Johnsen UL. Randomised, double blind,
placebo controlled trial of penicillin V and amoxycillin in treatment of
acute sinus infections in adults. Br Med J. 1996;313:325–329
11. Axelsson A, Chidekel N, Grebelius N, Jensen C. Treatment of acute
maxillary sinusitis. Acta Otolaryngol. 1970;70:71–76
12. Williams JW, Sinel DL, Roberts L, Samsa GP. Clinical evaluation for
sinusitis. Making the diagnosis by history and physical examination.
Ann Intern Med. 1992;117:705–710
13. Gwaltney J, Sydnor A, Sande M. Etiology and antimicrobial treatment
of acute sinusitis. Ann Otol Rhinol Laryngol. 1981;90:68 –71
14. Hamory BH, Sande MA, Sydnor A, Seale DL, Gwaltney JM. Etiology
and antimicrobial therapy of acute maxillary sinusitis. J Infect Dis.
1979;139:197–202
15. Gwaltney JM, Hendley JO, Simon G, Jordan WS. Rhinovirus infections
in an industrial population. JAMA. 1967;202:158 –164
16. Farr BM, Conner EM, Betts RF, Oleske J, Minnefor A, Gwaltney JM. Two
randomized controlled trials of zinc gluconate lozenge therapy of ex
perimentally induced rhinovirus colds. Antimicrob Agents Chemother.
1987;31:1183–1187
17. Gohd R. The common cold. N Engl J Med. 1954;250:687– 691
18. Hays GC, Mullard JE. Can nasal bacterial flora be predicted from
clinical findings? Pediatrics. 1972;49:596 –599
19. Wald E, Milmoe G, Bowen A, Ledesma-Medina J, Salamon N, Blue
stone C. Acute maxillary sinusitis in children. N Engl J Med. 1981;
304:749 –754
20. Wald ER. Purulent nasal discharge. Pediatr Infect Dis J. 1991;10:329 –333
21. Wald ER. Management of sinusitis in infants and children. Pediatr Infect
Dis J. 1988;7:449 – 452
22. Wald E, Reilly J, Casselbrant M, et al. Treatment of acute maxillary
sinusitis in childhood: a comparative study of amoxicillin and cefaclor.
J Pediatr. 1984;104:297–302
23. Kogutt MS, Swischuk LE. Diagnosis of sinusitis in infants and children.
Pediatrics. 1973;52:121–124
24. Diament M. The diagnosis of sinusitis in infants and children: x-ray,
computed tomography, and magnetic resonance imaging. J Allergy Clin
Immunol. 1992;90:442– 444
25. Arruda LK, Mimica IM, Sole D, et al. Abnormal maxillary sinus radio
graphs in children: do they represent bacterial infection? Pediatrics.
1990;85:553–558
26. Axelsson A, Chidekel N. Symptomatology and bacteriology correlated
to radiological findings in acute maxillary sinusitis. Acta Otolaryngol.
1972;74:118 –122
27. Glasier CM, Ascher DP, Williams KD. Incidental paranasal sinus ab
normalities on CT of children. Clinical correlations. AJNR Am J Neuro
radiol. 1986;7:861– 864
28. McAlister WH, Lusk R, Muntz HR. Comparison of plain radiographs
and coronal CT scans in infants and children with recurrent sinusitis.
AJR Am J Roentgenol. 1989;153:1259 –1264
29. Glasier CM, Mallory GB, Steele RW. Significance of opacification of the
maxillary and ethmoid sinuses in infants. J Pediatr. 1989;114:45–50
30. Havas TE, Motbey JA, Gullane PJ. Prevalence of incidental abnormali
ties on computed tomographic scans of the paranasal sinuses. Arch
Otolaryngol Head Neck Surg. 1988;114:856 – 859
31. van Buchem FL, Knottnerus JA, Schrijnemaekers VJJ, Peeters MF. Pri
mary care based randomised placebo-controlled trial of antibiotic treat
ment in acute maxillary sinusitis. Lancet. 1997;349:683– 687
32. Wald E. Sinusitis in children. N Engl J Med. 1992;326:319 –323
33. Williams JW, Holleman DR, Samsa GP, Simel DL. Randomized con
trolled trial of 3 vs 10 days of trimethoprim/sulfamethoxazole for acute
maxillary sinusitis. JAMA. 1995;273:1015–1021
SUPPLEMENT 177
plicated viral URIs. Day time cough is less com
mon and may indicate sinus drainage.21
Sinusitis also may be diagnosed among children
who have URI accompanied in the first several
days by specific signs and symptoms indicative of
acute sinus inflammation. These severe signs and
symptoms may include high fever (�39°C), persis
tent fever, periorbital swelling, facial pain, or den
tal pain.21 Sinusitis presenting with more severe
URI symptoms is much less common than sinusitis
presenting with persistent, unimproved URI
symptoms.7,22
Even with application of the strict criteria, some
children who do not have bacterial sinusitis will be
identified for treatment. In a study of 171 children
with nasal discharge or cough lasting from 10 to 30
days, 80% had abnormal maxillary sinus radio
graph findings.9 In another study of the microbi
ology and treatment of acute maxillary sinusitis,
sinus radiography was performed on children 1 to
16 years of age who presented with prolonged
respiratory symptoms (ie, nasal discharge or day
time cough, or both, for 10 to 30 days without
improvement) or severe respiratory symptoms, de
fined by concurrent fever (�39°C) and purulent
rhinorrhea for 3 to 4 days. Fifty children met these
strict clinical criteria and had abnormal radio
graphic findings in at least one of their maxillary
sinuses. Aspiration of the affected sinuses and cul
ture of the material demonstrated that a bacterial
pathogen could be recovered from 70% of these
children.22 Taking these studies together, recovery
of pathogenic bacteria would be expected from
only 56% (ie, 80% � 70%) of children fulfilling
these clinical criteria.
The common cold often includes radiologic ev
idence of sinus involvement; therefore, radio
graphs should be used and interpreted with cau
tion. They may be indicated 1) when episodes of
sinusitis are recurrent, 2) when complications are
suspected, or 3) when the diagnosis is unclear.
Sinusitis is usually a clinical diagnosis; however, in
some circumstances radiography of the sinuses may
be needed to confirm the clinical impression. Find
ings of sinusitis on plain films, computed tomogra
phy (CT), or magnetic resonance imaging include
air–fluid levels, opacification, or mucosal thickening
of �4 mm.22,23 Normal findings on sinus films make
the diagnosis of sinusitis highly unlikely, but abnor
mal findings are only moderately helpful in confirm
ing the diagnosis of acute bacterial sinusitis, because
other conditions including the common cold will
result in abnormal radiographic findings.19,24 –27 CT or
magnetic resonance imaging can be used for more
detailed examination of the sinuses than that af
forded by plain films. Like plain films, these studies
are rarely needed in acute infections unless accom
panied by intracranial or intraorbital complications.
Radiologic investigation should be reserved for spe
cific indications. These include confirming clinical
diagnoses of recurrent sinus infections; evaluating
children with persistent, complicated, or severe in
fections; and situations in which sinus surgery is
being contemplated.24
176 SUPPLEMENT
Radiographic studies performed early in the
course of a respiratory illness are not helpful for
diagnosis of sinusitis, because viral infections of
the upper respiratory tract can themselves cause
mucosal edema, obstruction of the ostiomeatal
complex, and fluid accumulation. Patients with
uncomplicated viral infections may exhibit not
only the same clinical signs and symptoms as those
with bacterial sinusitis (eg, pressure, congestion) but
the same abnormal radiographic findings as well.6 A
study of 31 adults evaluated by CT in the first 48 to 96
hours of uncomplicated viral respiratory illnesses
showed that almost 90% had abnormalities of one or
both maxillary-sinus cavities.5 After 2 weeks, these
findings resolved spontaneously or improved for 79%
of individuals reexamined; none had received antimi
crobial therapy.
In young children, the sinuses may not be devel
oped fully, making radiologic findings difficult to
interpret. Maxillary and ethmoid sinuses are
present at birth, although they are very small.
Frontal and sphenoid sinuses begin to appear at
�5 or 6 years of age but do not become fully
developed until adolescence. In a small proportion
of children, the frontal sinuses may not develop at
all or may develop only unilaterally. Misinterpret
ing absent sinuses as opacified sinuses in children
and adolescents can lead to overdiagnosis of sinus
itis.28 For this reason, sinus films should be inter
preted with great caution for children �1 year of
age.29
There are no radiographic images that alone confirm
a diagnosis of bacterial sinusitis; it is only in the setting
of prolonged symptoms suggestive of a bacterial su
perinfection that radiographic images can support such
a diagnosis. Abnormal images reflect inflammation;
they do not disclose whether the inflammation is viral,5
bacterial,19,25 or allergic30 in origin.
Initial Antimicrobial Treatment of Acute Sinusitis
Should Be With the Most Narrow-spectrum Agent That
Is Active Against the Likely Pathogens
Acute sinusitis is usually caused by the same
bacterial pathogens that cause acute otitis media
(Streptococcus pneumoniae, Haemophilus influenzae
(usually nontypeable), and Moraxella catarrhalis).
In studies in which microbiologic agents are iden
tified by culture of fluid aspirated from the max
illary sinuses of children and adults, S pneumoniae
accounted for 30% to 66% of isolates, H influenzae
and M catarrhalis each for 20%, and viral pathogens
alone for �10% of episodes.11,13,19,25 A study of 30
children with clinical and radiographic findings of
maxillary sinusitis who underwent aspiration of
the maxillary sinus demonstrated recovery of a
bacterial agent in 77% and a virus in 7%.19 Al
though the bacteria isolated from the sinuses were
usually found in the cultures of the nasopharynx,
they were not predictably the predominant spe
cies, suggesting that nasopharyngeal cultures are
not useful to predict the sinus pathogen.
As with acute otitis media, acute sinusitis often
will resolve even without antimicrobial therapy.
A double-blind, placebo-controlled antimicrobial
 cough without improvement for �10 to 14 days),
or more severe upper respiratory tract signs and
symptoms (ie, fever �39°C, facial swelling, facial
pain).
2. The common cold often includes radiologic evi
dence of sinus involvement; therefore, radio
graphs should be used and interpreted with cau
tion. They may be indicated under the following
conditions: when episodes of sinusitis are recur
rent, when complications are suspected, or when
the diagnosis is unclear.
3. Initial antimicrobial treatment of acute sinusitis
should be with the most narrow-spectrum agent
that is active against the likely pathogens.
BACKGROUND AND JUSTIFICATION
E
ach year, millions of children are diagnosed
with sinusitis and prescribed an antimicro
bial agent.1 It is estimated that most pre
school and school children have three to eight
acute viral upper respiratory tract illnesses (URIs)
annually and that bacterial sinusitis complicates
0.5% to 5.0% of these.2– 4 Uncomplicated viral URIs
produce congestion and inflammation of both the
nasal and the sinus mucosa; therefore, they should
be viewed as viral rhinosinusitis infections.5,6 Be
cause viral rhinosinusitis is at least 20 to 200 times
more common than bacterial sinusitis, the use of
appropriate diagnostic criteria to identify accu
rately the small subgroup of patients who may
have a bacterial infection of the sinuses is a pri
mary goal in promoting the judicious use of anti
microbial agents.
Sinusitis is defined as inflammation of the sinus
mucosa. It can be caused by either infectious or
noninfectious processes. Episodes of sinusitis may
be categorized on the basis of duration of symp
toms as acute (symptoms lasting 10 to 30 days),
subacute (symptoms lasting 30 days to 3 months),
or chronic (symptoms lasting �3 months). The
major causative agents differ according to these
categories; the principles described here focus on
acute sinusitis.
The precipitating event in acute sinusitis is usu
ally a viral upper respiratory tract infection that
produces mucosal inflammation.7 The inflamma
tion may result in obstruction of the sinus ostia
and trapping of fluid in the sinus cavities. Without
proper drainage, bacteria that are part of the nor
mal upper respiratory tract flora can be trapped
and proliferate in this space. The pathophysiology
of acute sinusitis is similar to that of acute otitis
media; sinusitis and otitis media may coexist.8 In
addition, as with acute otitis media, �60% of si
nusitis episodes will resolve or improve spontane
ously without antimicrobial therapy.9 –11 By care
fully applying specific clinical criteria for the
diagnosis of acute sinusitis, it should be possible to
limit the use of antimicrobial agents to situations
in which they are most likely to be beneficial.
EVIDENCE SUPPORTING PRINCIPLES
Clinical diagnosis of bacterial sinusitis requires
the following: 1) prolonged nonspecific upper re
spiratory signs and symptoms (ie, rhinosinusitis
and cough without improvement for >10 to 14
days), or 2) more severe upper respiratory tract
signs and symptoms (ie, fever >39°C, facial swell
ing, facial pain).
Judicious antimicrobial therapy for bacterial si
nusitis depends on limiting the use of these agents
to children who have a high likelihood of benefit
ing from treatment. Therefore, the diagnosis of
bacterial sinusitis should be limited to those chil
dren with clinical signs and symptoms that are
most likely to reflect true disease. Acute sinusitis
among older children and adults occasionally can
be diagnosed by the presence of classic signs or
symptoms, such as sinus tenderness, tooth pain,
headache, and high fever.12–14 However, in young
children, these classic signs or symptoms are al
most never present.
Uncomplicated URIs and bacterial sinusitis may be
indistinguishable solely on the basis of the clinical
features observed. The duration of the signs and
symptoms rather than their mere presence, is most
discriminatory in distinguishing these two condi
tions. Therefore, it is important to review and under
stand the natural history of URIs.
The natural history of uncomplicated viral URI
has been well defined in studies of patients with
documented community-acquired viruses as well
as in experimentally induced rhinovirus URI
among adult volunteers.15–17 Sore throat and sneez
ing commonly occur early in the course of illness
and tend to resolve over 3 to 6 days. Fever, mal
aise, and myalgia are reported by a smaller pro
portion of patients, but also resolve by day 6 to 8.
Cough, nasal discharge, and nasal obstruction are
common and persist; up to 25% of patients still
have these symptoms at 14 days.4,15,17 Involvement
of the paranasal sinuses, with thickened mucosa,
infundibular occlusion, and occasional air–fluid
levels, is a consistent aspect of uncomplicated viral
URI.5
Although some believe that mucopurulent rhinitis
(thick, opaque, or discolored nasal discharge) indicates
the presence of bacterial sinusitis, this sign should be
recognized as part of the natural course of a nonspe
cific, uncomplicated viral URI. Natural history studies
of experimental rhinovirus colds reveal that nasal dis
charge changes from clear to purulent during the first
few days of illness.17,18 Furthermore, the color and char
acteristics of the discharge do not predict whether a
bacterial pathogen will be isolated.18
Acute bacterial sinusitis can be diagnosed in
children who have persistent symptoms without
improvement by 10 to 14 days; however, children
with rhinorrhea or cough that is improving by day
10 of illness are likely to have an uncomplicated
viral URI.4 Persistent clinical findings usually in
clude nasal discharge and day time cough. The
nasal discharge may be of any color or quality
(thick, thin, clear, or purulent); thus, the character
of the discharge is not helpful in distinguishing
sinus fluid infected with a bacterial pathogen from
uninfected fluid.19,20 Persistent nocturnal cough is
nonspecific and may be observed during uncom-
SUPPLEMENT 175
 cal pharyngitis. Am J Dis Child. 1977;131:514
6. Wigton RS, Connor JL, Centor RM. Transportability of a decision rule
for the diagnosis of streptococcal pharyngitis. Arch Intern Med. 1986;146:
81– 83
7. American Academy of Pediatrics. Group A streptococcal infections. In:
Peter G, ed. 1997 Red Book. Report of the Committee on Infectious Diseases.
24th ed. Elk Grove Village, IL: American Academy of Pediatrics; 1997:
483– 494
8. Gerber MA, Randolph MF, DeMeo KK. Liposome immunoassay for
rapid identification of group A streptococci directly from throat swabs.
J Clin Microbiol. 1990;28:1463–1464
9. Harbeck RJ, Teague J, Crossen GR, Maul DM, Childers PL. Novel, rapid
optical immunoassay technique for detection of group A streptococci
from pharyngeal specimens: comparison with standard culture meth
ods. J Clin Microbiol. 1993;31:839 – 844
10. Heiter BJ, Bourbeau PP. Comparison of two rapid streptococcal antigen
detection assays with culture for diagnosis of streptococcal pharyngitis.
J Clin Microbiol. 1995;33:1408 –1410
11. Gerber MA, Tanz RR, Kabat W, et al. Optical immunoassay test for group
A �-hemolytic streptococcal pharyngitis. JAMA. 1997;277:899 –903
12. Dale JC, Vetter EA, Contezac JM, Iverson LK, Wollan PC, Cockerill FR
III. Evaluation of two rapid antigen assays, BioStar Strep A OIA and
Pacific Biotech CARDS O. S., and culture for detection of group A
streptococci in throat swabs. J Clin Microbiol. 1994;32:2698 –2701
13. Roe M, Kishiyama C, Davidson K, Schaefer L, Todd J. Comparison of
BioStar A OIA optical immune assay, Abbott TestPack Plus Strep A, and
culture with selective media for diagnosis of group A streptococcal
pharyngitis. J Clin Microbiol. 1995;33:1551–1553
14. Baker DM, Cooper RM, Rhodes C, Weymouth LA, Dalton HP. Superiority
of conventional culture technique over rapid detection of group A Strep
tococcus by optical immunoassay. Diagn Microbiol Infect Dis. 1995;21:61– 64
15. Huck W, Reed BD, French T, Mitchell RS. Comparison of the Directigen
1–2–3 group A strep test with culture for detection of group A beta-
hemolytic streptococci. J Clin Microbiol. 1989;27:1715–1718
16. Donatelli J, Macone A, Goldmann DA, et al. Rapid detection of group A
streptococci: comparative performance by nurses and laboratory tech
nologists in pediatric satellite laboratories using three test kits. J Clin
Microbiol. 1992;30:138 –142
17. Wenger DL, Witte DL, Schrantz RD. Insensitivity of rapid antigen
detection methods and single blood agar plate culture for diagnosing
streptococcal pharyngitis. JAMA. 1992;267:695– 697
18. Brien JH, Bass JW. Streptococcal pharyngitis: optimal site for throat
culture. J Pediatr. 1985;106:781–783
19. Rosenstein BJ, Markowitz M, Gordis L. Accuracy of throat cultures
Acute Sinusitis—Principles of Judicious Use of Antimicrobial Agents
Katherine L. O’Brien, MD*; Scott F. Dowell, MD, MPH*; Benjamin Schwartz, MD*; S. Michael Marcy, MD‡;
William R. Phillips, MD, MPH§; and Michael A. Gerber, MD�
ABSTRACT. Establishing an accurate diagnosis of
bacterial sinusitis is challenging but critical, because
viral rhinosinusitis is at least 20 to 200 times more
common than bacterial infection of the sinuses. Strict
criteria for clinical diagnosis that require either pro
longed and persistent symptoms or an acute severe
presentation are supported with published evidence.
From the *Childhood and Respiratory Diseases Branch, DBMD, National
Center for Infectious Diseases, Centers for Disease Control and Prevention,
Atlanta, Georgia; ‡Kaiser Permanente, Panorama City, California; §North
ABBREVIATIONS. URI, upper respiratory tract illness; CT, com
west Family Medicine, Seattle, Washington; and �Connecticut Children’s
puted tomography.
Medical Center, Hartford, Connecticut.
Received for publication Aug 8, 1997; accepted Sep 11, 1997.
Reprint requests to (S.F.D.) Centers for Disease Control and Prevention,
Mailstop C-23, 1600 Clifton Rd, NE, Atlanta, GA 30333.
1. Clinical diagnosis of bacterial sinusitis requires
PEDIATRICS (ISSN 0031 4005). Copyright © 1998 by the American Acad
the following: prolonged nonspecific upper respi
emy of Pediatrics.
ratory signs and symptoms (ie, rhinosinusitis and
174 SUPPLEMENT
processed in physicians’ offices. J Pediatr. 1970;76:606 – 609
20. Kellogg JA. Suitability of throat culture procedures for detection of
group A streptococci and as reference standards for evaluation of
streptococcal antigen detection kits. J Clin Microbiol. 1990;28:165–169
21. Holmberg SD, Faich GA. Streptococcal pharyngitis and acute rheumatic
fever in Rhode Island. JAMA. 1983;250:2307–2312
22. Middleton DB, D’Amico FD, Merenstein JH. Standardized symptomatic
treatment versus penicillin as initial therapy for streptococcal pharyn
gitis. J Pediatr. 1988;113:1089 –1094
23. Del Mar C. Managing sore throat: a literature review. II. Do antibiotics
confer benefit? Med J Aust. 1992;156:644 – 649
24. Gerber MA, Randolph MF, DeMeo KK, Kaplan EL. Lack of impact of
early antibiotic therapy for streptococcal pharyngitis on recurrence
rates. J Pediatr. 1990;117:853– 858
25. Putto A. Febrile exudative tonsillitis: viral or streptococcal? Pediatrics.
1987;80:6 –12
26. Denson MR. Viral pharyngitis. Semin Pediatr Infect Dis. 1995;6:62– 68
27. Waagner D. Arcanobacterium haemolyticum: biology of the organism and
diseases in man. Pediatr Infect Dis J. 1991;10:933–939
28. Lieu TA, Fleisher GR, Schwartz JS. Cost-effectiveness of rapid latex
agglutination testing and throat culture for streptococcal pharyngitis.
Pediatrics. 1990;85:246 –256
29. Shulman ST, Gerber MA, Tanz RR, Markowitz M. Streptococcal
pharyngitis: the case for penicillin therapy. Pediatr Infect Dis J. 1994;13:1–7
30. Schwartz RH, Wientzen RL, Pedreira F, Feroli EJ, Mella GW, Guandolo
VL. Penicillin V for group A streptococcal pharyngotonsillitis. JAMA.
1981;246:1790 –1795
31. Gerber MA, Randolph MF, Chantary J, Wright LL, De Meo K, Kaplan
EL. Five vs ten days of penicillin V therapy for streptococcal pharyn
gitis. Am J Dis Child. 1987;141:224 –227
32. Pichichero ME, Margolis PA. A comparison of cephalosporins and
penicillins in the treatment of group A beta-hemolytic streptococcal
pharyngitis: a meta-analysis supporting the concept of microbial co
pathogenicity. Pediatr Infect Dis J. 1991;10:275–281
33. Seppala H, Nissinen A, Jarvinen H, et al. Resistance to erythromycin in
group A streptococci. N Engl J Med 1992;326:292–297
34. Fujita K, Murono K, Yoshikawa M, Murai T. Decline of erythromycin
resistance of group A streptococci in Japan. Pediatr Infect Dis J. 1994;13:
1075–1078
35. Seppala H, Klaukka T, Vuopio-Varkila J, et al. The effect of changes
in the consumption of macrolide antibiotics on erythromycin resis
tance in group A streptococci in Finland. N Engl J Med. 1997;337:
441– 446
Radiographic imaging of the sinuses should be used only
in very selected circumstances. A majority of patients with
the common cold will meet radiographic criteria for sinus
itis early in the course of their illness. For patients meeting
these strict criteria, an appropriate narrow-spectrum antimi
crobial agent will be of modest benefit compared with
symptomatic treatment alone. Pediatrics 1998;101:174–177;
sinusitis, diagnosis, antimicrobial therapy, mucopurulent
rhinitis, antimicrobial resistance, pediatrics.
PRINCIPLES
 cal pharyngitis. Am J Dis Child. 1977;131:514
6. Wigton RS, Connor JL, Centor RM. Transportability of a decision rule
for the diagnosis of streptococcal pharyngitis. Arch Intern Med. 1986;146:
81– 83
7. American Academy of Pediatrics. Group A streptococcal infections. In:
Peter G, ed. 1997 Red Book. Report of the Committee on Infectious Diseases.
24th ed. Elk Grove Village, IL: American Academy of Pediatrics; 1997:
483– 494
8. Gerber MA, Randolph MF, DeMeo KK. Liposome immunoassay for
rapid identification of group A streptococci directly from throat swabs.
J Clin Microbiol. 1990;28:1463–1464
9. Harbeck RJ, Teague J, Crossen GR, Maul DM, Childers PL. Novel, rapid
optical immunoassay technique for detection of group A streptococci
from pharyngeal specimens: comparison with standard culture meth
ods. J Clin Microbiol. 1993;31:839 – 844
10. Heiter BJ, Bourbeau PP. Comparison of two rapid streptococcal antigen
detection assays with culture for diagnosis of streptococcal pharyngitis.
J Clin Microbiol. 1995;33:1408 –1410
11. Gerber MA, Tanz RR, Kabat W, et al. Optical immunoassay test for group
A �-hemolytic streptococcal pharyngitis. JAMA. 1997;277:899 –903
12. Dale JC, Vetter EA, Contezac JM, Iverson LK, Wollan PC, Cockerill FR
III. Evaluation of two rapid antigen assays, BioStar Strep A OIA and
Pacific Biotech CARDS O. S., and culture for detection of group A
streptococci in throat swabs. J Clin Microbiol. 1994;32:2698 –2701
13. Roe M, Kishiyama C, Davidson K, Schaefer L, Todd J. Comparison of
BioStar A OIA optical immune assay, Abbott TestPack Plus Strep A, and
culture with selective media for diagnosis of group A streptococcal
pharyngitis. J Clin Microbiol. 1995;33:1551–1553
14. Baker DM, Cooper RM, Rhodes C, Weymouth LA, Dalton HP. Superiority
of conventional culture technique over rapid detection of group A Strep
tococcus by optical immunoassay. Diagn Microbiol Infect Dis. 1995;21:61– 64
15. Huck W, Reed BD, French T, Mitchell RS. Comparison of the Directigen
1–2–3 group A strep test with culture for detection of group A beta-
hemolytic streptococci. J Clin Microbiol. 1989;27:1715–1718
16. Donatelli J, Macone A, Goldmann DA, et al. Rapid detection of group A
streptococci: comparative performance by nurses and laboratory tech
nologists in pediatric satellite laboratories using three test kits. J Clin
Microbiol. 1992;30:138 –142
17. Wenger DL, Witte DL, Schrantz RD. Insensitivity of rapid antigen
detection methods and single blood agar plate culture for diagnosing
streptococcal pharyngitis. JAMA. 1992;267:695– 697
18. Brien JH, Bass JW. Streptococcal pharyngitis: optimal site for throat
culture. J Pediatr. 1985;106:781–783
19. Rosenstein BJ, Markowitz M, Gordis L. Accuracy of throat cultures
Acute Sinusitis—Principles of Judicious Use of Antimicrobial Agents
Katherine L. O’Brien, MD*; Scott F. Dowell, MD, MPH*; Benjamin Schwartz, MD*; S. Michael Marcy, MD‡;
William R. Phillips, MD, MPH§; and Michael A. Gerber, MD�
ABSTRACT. Establishing an accurate diagnosis of
bacterial sinusitis is challenging but critical, because
viral rhinosinusitis is at least 20 to 200 times more
common than bacterial infection of the sinuses. Strict
criteria for clinical diagnosis that require either pro
longed and persistent symptoms or an acute severe
presentation are supported with published evidence.
From the *Childhood and Respiratory Diseases Branch, DBMD, National
Center for Infectious Diseases, Centers for Disease Control and Prevention,
Atlanta, Georgia; ‡Kaiser Permanente, Panorama City, California; §North
ABBREVIATIONS. URI, upper respiratory tract illness; CT, com
west Family Medicine, Seattle, Washington; and �Connecticut Children’s
puted tomography.
Medical Center, Hartford, Connecticut.
Received for publication Aug 8, 1997; accepted Sep 11, 1997.
Reprint requests to (S.F.D.) Centers for Disease Control and Prevention,
Mailstop C-23, 1600 Clifton Rd, NE, Atlanta, GA 30333.
1. Clinical diagnosis of bacterial sinusitis requires
PEDIATRICS (ISSN 0031 4005). Copyright © 1998 by the American Acad
the following: prolonged nonspecific upper respi
emy of Pediatrics.
ratory signs and symptoms (ie, rhinosinusitis and
174 SUPPLEMENT
processed in physicians’ offices. J Pediatr. 1970;76:606 – 609
20. Kellogg JA. Suitability of throat culture procedures for detection of
group A streptococci and as reference standards for evaluation of
streptococcal antigen detection kits. J Clin Microbiol. 1990;28:165–169
21. Holmberg SD, Faich GA. Streptococcal pharyngitis and acute rheumatic
fever in Rhode Island. JAMA. 1983;250:2307–2312
22. Middleton DB, D’Amico FD, Merenstein JH. Standardized symptomatic
treatment versus penicillin as initial therapy for streptococcal pharyn
gitis. J Pediatr. 1988;113:1089 –1094
23. Del Mar C. Managing sore throat: a literature review. II. Do antibiotics
confer benefit? Med J Aust. 1992;156:644 – 649
24. Gerber MA, Randolph MF, DeMeo KK, Kaplan EL. Lack of impact of
early antibiotic therapy for streptococcal pharyngitis on recurrence
rates. J Pediatr. 1990;117:853– 858
25. Putto A. Febrile exudative tonsillitis: viral or streptococcal? Pediatrics.
1987;80:6 –12
26. Denson MR. Viral pharyngitis. Semin Pediatr Infect Dis. 1995;6:62– 68
27. Waagner D. Arcanobacterium haemolyticum: biology of the organism and
diseases in man. Pediatr Infect Dis J. 1991;10:933–939
28. Lieu TA, Fleisher GR, Schwartz JS. Cost-effectiveness of rapid latex
agglutination testing and throat culture for streptococcal pharyngitis.
Pediatrics. 1990;85:246 –256
29. Shulman ST, Gerber MA, Tanz RR, Markowitz M. Streptococcal
pharyngitis: the case for penicillin therapy. Pediatr Infect Dis J. 1994;13:1–7
30. Schwartz RH, Wientzen RL, Pedreira F, Feroli EJ, Mella GW, Guandolo
VL. Penicillin V for group A streptococcal pharyngotonsillitis. JAMA.
1981;246:1790 –1795
31. Gerber MA, Randolph MF, Chantary J, Wright LL, De Meo K, Kaplan
EL. Five vs ten days of penicillin V therapy for streptococcal pharyn
gitis. Am J Dis Child. 1987;141:224 –227
32. Pichichero ME, Margolis PA. A comparison of cephalosporins and
penicillins in the treatment of group A beta-hemolytic streptococcal
pharyngitis: a meta-analysis supporting the concept of microbial co
pathogenicity. Pediatr Infect Dis J. 1991;10:275–281
33. Seppala H, Nissinen A, Jarvinen H, et al. Resistance to erythromycin in
group A streptococci. N Engl J Med 1992;326:292–297
34. Fujita K, Murono K, Yoshikawa M, Murai T. Decline of erythromycin
resistance of group A streptococci in Japan. Pediatr Infect Dis J. 1994;13:
1075–1078
35. Seppala H, Klaukka T, Vuopio-Varkila J, et al. The effect of changes
in the consumption of macrolide antibiotics on erythromycin resis
tance in group A streptococci in Finland. N Engl J Med. 1997;337:
441– 446
Radiographic imaging of the sinuses should be used only
in very selected circumstances. A majority of patients with
the common cold will meet radiographic criteria for sinus
itis early in the course of their illness. For patients meeting
these strict criteria, an appropriate narrow-spectrum antimi
crobial agent will be of modest benefit compared with
symptomatic treatment alone. Pediatrics 1998;101:174–177;
sinusitis, diagnosis, antimicrobial therapy, mucopurulent
rhinitis, antimicrobial resistance, pediatrics.
PRINCIPLES
group in whom classical group A streptococcal
pharyngitis occurs less often.
Pharyngeal irritation occurs frequently in persons
with rhinovirus, corona virus, parainfluenza, influ
enza, adenovirus, and Epstein–Barr virus infection.26
The signs and symptoms of pharyngitis associated
with these viral infections overlap substantially with
those of group A streptococcal pharyngitis; however,
differences in clinical presentation also may exist.
Children with viral pharyngitis often have promi
nent extrapharyngeal signs and symptoms such as
nasal discharge, cough, and hoarseness. Adenoviral
infection, a common cause of prolonged exudative
pharyngitis, may be accompanied by conjunctivitis
(pharyngoconjunctival fever), whereas an Epstein–
Barr virus infection may have other signs of infec
tious mononucleosis (eg, generalized lymphadenop
athy, splenomegaly). Coxsackie viruses and herpes
simplex viruses often cause stomatitis as well as
pharyngitis; vesicular or ulcerative lesions may be
noted on examination.26
Bacteria other than group A Streptococcus are rare
causes of pharyngitis, and many such infections can
be recognized by extrapharyngeal signs.1 Other �-he
molytic streptococci (groups C and G) may be carried
in the pharynx asymptomatically or may cause in
fection resembling that caused by group A strepto
cocci; the course of these infections is self-limited,
and rheumatic fever does not occur. These �-hemo
lytic streptococci could be identified by culture but
not by an antigen-detection test. Neisseria gonorrhea
pharyngitis is rare and typically occurs among ado
lescents; a history of sexual activity would be sug
gestive of this etiology, and pharyngitis may be ac
companied by signs of genital infection or a rash.
Arcanobacterium haemolyticum infection is uncommon
in the United States, characteristically occurs in ad
olescents, and often presents with a scarlatiniform
rash.27 Diphtheria is a rare cause of pharyngitis in
well-immunized populations and may be recognized
by an asymmetric gray pharyngeal membrane that
may extend beyond the borders of the anterior ton
sillar pillars onto the soft palate and/or the uvula.
Because each of these etiologic agents is uncommon
and sequelae such as acute rheumatic fever do not
occur, there is no rationale for empiric antimicrobial
therapy of pharyngitis in children.
The significance of Mycoplasma pneumoniae and
Chlamydia pneumoniae as causes of pharyngitis is un
clear; these infections usually are accompanied by
other signs of respiratory illness, especially cough.
The benefit of antimicrobial therapy for the pharyn
gitis caused by these agents has not been docu
mented.
Because the large majority of pharyngitis episodes
are not caused by group A streptococci, empiric an
timicrobial therapy would result in substantial over-
treatment. The widespread availability of accurate,
inexpensive, diagnostic tests for group A streptococ
cal infections makes a diagnostic strategy of culture
and/or antigen-detection testing for children with
suspected streptococcal pharyngitis both effective
and cost-effective,28 and represents an optimal ap
proach to avoiding the overuse of antibiotics. This
strategy has been presented in algorithm form.1
Penicillin Remains the Drug of Choice for Treating
Group A Streptococcal Pharyngitis
Penicillin has proven highly effective as therapy
for group A streptococcal pharyngitis and in pre
venting acute rheumatic fever. Because of its safety,
efficacy, relatively narrow spectrum, and low cost, it
remains the drug of choice for this indication.
Amoxicillin is an acceptable alternative and often is
prescribed because it is more palatable than penicil
lin and the cost is comparable. Because of its broader
antimicrobial spectrum, however, use of amoxicillin
results in greater selective pressure for the develop
ment of antimicrobial resistance. Penicillin therapy,
administered for 10 days, results in bacteriologic and
clinical cure in �90% of children with group A strep
tococcal pharyngitis.29 Shorter courses of therapy
have been less effective.30,31 Although microbiologi
cal cure rates are slightly higher in children treated
with cephalosporins,32 this may reflect greater effi
cacy in eradicating the organism from children who
actually are carriers rather than improved outcome
in those with acute infection.29 Carriers are at very
low risk for developing acute rheumatic fever and
transmitting infection; therefore, the excess cost of
cephalosporin therapy and the greater selective pres
sure for resistance associated with use of these
broader-spectrum agents are disadvantages that out
weigh the small increment in group A streptococcal
eradication. To date, no group A streptococci resis
tant to �-lactam antibiotics have been identified. Re
sistance to erythromycin, an alternative therapy for
patients who are allergic to penicillin, has been re
ported in several areas.33–35 In both Finland and
Japan, increased rates of erythromycin resistance oc
curred coincident with increasing levels of macrolide
use. As macrolide use subsequently declined—in
Finland as the result of national guidelines recom
mending decreased use of erythromycin for respira
tory and skin infections—so too has the proportion
of erythromycin-resistant group A streptococci.34,35
Because resistance to extended spectrum macrolides
(eg, clarithromycin) or azolides (eg, azithromycin)
would be similar to that for erythromycin and these
agents exert selective pressure for resistance over a
broader range of bacterial pathogens, their use in
treating pharyngitis should be discouraged.
ACKNOWLEDGMENTS
We thank Drs Leah Raye Mabry and Doug Long and members
of the Committee on Infectious Diseases of the American Acad
emy of Pediatrics for their careful review of this document.
REFERENCES
1. Tanz RR, Shulman ST. Diagnosis and treatment of group A streptococ
cal pharyngitis. Semin Pediatr Infect Dis. 1995;6:69 –78
2. Rammelkamp CH. Rheumatic heart disease—a challenge. Circulation.
1958;17:842– 851
3. Stillerman M, Bernstein SH. Streptococcal pharyngitis: evaluation of
clinical syndromes in diagnosis. Am J Dis Child. 1961;101:476 – 489
4. Poses RM, Cebul RD, Collins M, et al. The accuracy of experienced
physicians’ probability estimates for patients with sore throat: implica
tions for decision making. JAMA. 1985;254:925–929
5. Breese BB. A simple scorecard for the tentative diagnosis of streptococ-
SUPPLEMENT 173
by viral agents, treatment of all children with this
illness would result in substantial unnecessary anti
microbial use. The recommendations that follow pro
vide an approach to the diagnosis and treatment of
children with pharyngitis that are consistent with
judicious antimicrobial use.
EVIDENCE IN SUPPORT OF PRINCIPLES
Diagnosis of Group A Streptococcal Pharyngitis Should
Be Made Using a Laboratory Test in Conjunction With
Clinical and Epidemiologic Findings
Symptoms of classic streptococcal pharyngitis in
clude acute onset of pharyngeal pain, dysphagia, and
fever. Malaise, headache, abdominal pain, and vom
iting occur commonly. Rhinorrhea, cough, hoarse
ness, conjunctivitis, and diarrhea are uncommon and
strongly suggest a viral etiology. On examination,
the pharynx is erythematous, a patchy exudate often
is present on the posterior pharynx and tonsils, and
palatal petechiae may be observed. The anterior cer
vical lymph nodes often are enlarged and tender.3
Unfortunately, these clinical findings are neither
sensitive nor specific for group A streptococcal infec
tion. When a diagnosis is based on clinical impres
sion alone, physicians generally overestimate the
probability that patients have streptococcal infec
tion.4 Several schema have been developed to im
prove the ability to predict which patients will have
group A streptococcal pharyngitis by scoring clinical
and epidemiologic findings.2,5,6 None of these sys
tems, however, identifies accurately children who
need treatment and those who do not. Although the
negative predictive value of a low score is good and
may help guide a physician in deciding when a
diagnostic test is needed, the positive predictive
value of even the highest score is limited. In the
evaluation of one system among adults, only 54% of
patients in the most predictive group—those with a
history of fever, tonsillar exudate, anterior cervical
lymphadenopathy, and an absence of cough— had
group A streptococci identified by culture.6
Because the clinical presentation of pharyngitis
does not predict reliably the etiologic agent, when
group A streptococcal infection is suspected, diagno
sis should be based on results of a throat swab cul
ture or antigen-detection test with culture back-up.
Culture of a throat swab specimen is recommended
as the standard for diagnosis.7 Some studies report
the sensitivity of antigen-detection tests to be �90%
in carefully controlled clinical settings,8 –11 but such
tests often have proved less sensitive in routine clin
ical practice.12–17 Consequently, the American Acad
emy of Pediatrics recommends that if an antigen-
detection test is negative in a child with suspected
group A streptococcal pharyngitis, a culture also be
performed.7 Because the specificity of antigen-detec
tion tests is high, confirmation of a positive test is not
required.
Throat cultures may be false-negative if specimens
are obtained or cultured improperly. Samples should
be obtained by vigorous swabbing of both tonsillar
surfaces or fossae and the posterior pharynx; swab
bing the soft palate and uvula should be avoided,
172 SUPPLEMENT
because it dilutes the inoculum.18 Culture methods
are important as well. In one study, results of throat
cultures performed in five physicians’ offices were
compared with a duplicate swab cultured at a refer
ence laboratory. The sensitivities of cultures per
formed in the offices ranged from 73% to 100%;
errors occurred both in isolating group A strepto
cocci and in correctly identifying the organism.19 The
sensitivity of culture also has been reported to vary
depending on the laboratory methods used.17,20 For
both culture and antigen detection, the sensitivity of
the test is dependent on the quality of the specimen,
how well the assay is performed, and the experience
of the person reading the results.
Survey results indicate that many physicians initi
ate antimicrobial therapy for pharyngitis pending
results of throat culture and that antimicrobial ther
apy often is continued despite cultures being re
ported as negative.21 This approach results in sub
stantial antimicrobial overuse and obviates the
benefits of performing a culture. If antibiotics are
provided pending results of culture, physicians
should be diligent in contacting parents if cultures
are negative and should inform them to stop therapy
and discard any remaining antibiotics.
Because early antimicrobial therapy may limit
transmission of illness if the infection is caused by
group A streptococci and may facilitate a child’s
return to school or day care, appropriate therapy
should be initiated as soon as the diagnosis is sup
ported by a laboratory test. It is unclear, however,
whether immediate therapy offers a clinical benefit
compared with symptomatic treatment,22,23 and no
evidence suggests that early antimicrobial therapy
decreases recurrent infection24 or is necessary to pre
vent acute rheumatic fever.2 Negative consequences
of empirically starting therapy include selection of
resistant bacterial pathogens, the risk of hypersensi
tivity or other adverse reactions, and cost. Use of a
rapid antigen-detection test can help clinicians resist
pressure for immediate therapy, because a negative
result may facilitate immediate return to school or
day care.
Antimicrobial Therapy Should Not Be Given to a Child
With Pharyngitis in the Absence of Diagnosed
Group A Streptococcal or Other Bacterial Infection
Viral agents cause most pharyngitis episodes.
Even in patients with pharyngeal exudate and fe
ver, group A streptococci account for a minority of
infections. In one study, diagnostic tests for bacte
rial and viral pathogens were performed on 110
children who had exudative pharyngitis and fever
and had not been treated previously with antibi
otics. Group A streptococci were isolated from
only 12% of children, whereas viral infection was
documented from 31%. In addition, viral agents for
which diagnostic testing was not available, includ
ing rhinovirus and coronavirus, may have ac
counted for infection in some of the children in
whom no etiologic agent was identified.25 The pre
dominance of viral infection was especially noted
among children who were �3 years of age—a
 media. A double-blind crossover study in pediatric practice. N Engl
J Med. 1974;291:664 – 667
57. Schwartz RH, Puglise J, Rodriguez WJ. Sulphamethoxazole prophylaxis
in the otitis-prone child. Arch Dis Child. 1982;57:590 –593
58. Schuller DE. Prophylaxis of otitis media in asthmatic children. Pediatr
Infect Dis. 1983;2:280 –283
59. Liston TE, Foshee WS, Pierson WD. Sulfisoxazole chemoprophylaxis for
frequent otitis media. Pediatrics. 1983;71:524 –530
60. Varsano I, Volovitz B, Mimouni F. Sulfisoxazole prophylaxis of middle ear
effusion and recurrent acute otitis media. Am J Dis Child. 1985;139:632– 635
61. Gonzalez C, Arnold JE, Woody EA, et al. Prevention of recurrent acute
otitis media: chemoprophylaxis versus tympanostomy tubes. Laryngo
scope. 1986;96:1330 –1334
62. Paradise JL. Antimicrobial prophylaxis for recurrent acute otitis media.
Ann Otol Rhinol Laryngol. 1981;90(suppl):53–57
63. Goldstein NA, Sculerati N. Compliance with prophylactic antibiotics for
otitis media in a New York City clinic. Int J Pediatr Otorhinolaryngol.
1994;28:129 –140
64. Prellner K, Fogle-Hansson M, Jorgensen F, Kalm O, Kamme C. Prevention
of recurrent acute otitis media in otitis-prone children by intermittent
prophylaxis with penicillin. Acta Oto-Laryngologica. 1994;114:182–187
65. Heikkinen T, Ruuskanen O, Ziegler T, Waris M, Puhakka H. Short-term
use of amoxicillin-clavulanate during upper respiratory tract infection
for prevention of acute otitis media. J Pediatr. 1995;126:313–316
66. Berman S, Nuss R, Roark R, Huber-Navin C, Grose K, Herrera M.
Effectiveness of continuous vs. intermittent amoxicillin to prevent epi
sodes of otitis media. Pediatr Infect Dis J. 1992;11:63– 67
Pharyngitis—Principles of Judicious Use of Antimicrobial Agents
Benjamin Schwartz, MD*; S. Michael Marcy, MD‡; William R. Phillips, MD, MPH§;
Michael A. Gerber, MD�; and Scott F. Dowell, MD, MPH*
ABSTRACT. Accurate diagnosis of group A strepto
coccal pharyngitis and appropriate antimicrobial ther
apy are important, particularly to prevent nonsuppu
rative sequelae such as rheumatic fever. Most episodes
of sore throat, however, are caused by viral agents.
Clinical findings cannot reliably differentiate strepto
coccal from viral pharyngitis and most physicians tend
to overestimate the probability of a streptococcal in
fection based on history and physical examination
alone. Therefore, diagnosis should be based on results
of a throat culture or an antigen-detection test with
throat culture backup. Presumptively starting therapy
pending results of a culture is discouraged because
treatment often continues despite a negative test re
sult. Other bacterial causes of pharyngitis are uncom
mon and often can be diagnosed based on nonpharyn
geal findings. Penicillin remains the drug of choice for
streptococcal pharyngitis because of its effectiveness,
relatively narrow spectrum, and low cost. No group A
streptococci are resistant to �-lactam antibiotics. High
rates of resistance to macrolides has been documented
in several areas; in Finland, decreased national rates of
macrolide use led to a decline in the proportion of
From the *Childhood and Respiratory Diseases Branch, National Centers
for Infectious Diseases, Centers for Disease Control and Prevention,
Atlanta, Georgia; ‡Kaiser Permanente, Panorama City, California; §North
within 9 days of onset is effective in preventing acute
west Family Medicine, Seattle, Washington; and �Connecticut Children;s
rheumatic fever.2 In addition, treatment of group A
Medical Center, Hartford, Connecticut.
streptococcal infection may prevent suppurative
Reprint requests to (S.F.D.) Centers for Disease Control and Prevention,
Mailstop C-23, 1600 Clifton Rd, NE, Atlanta, GA 30333.
PEDIATRICS (ISSN 0031 4005). Copyright © 1998 by the American Acad
ness, and prevent the spread of infection. Neverthe
emy of Pediatrics.
less, because most episodes of sore throat are caused
67. Daly KA, Giebink GS, Lindgren B, et al. Randomized trial of the efficacy
of trimethoprim-sulfamethoxazole and prednisone in preventing post
tympanostomy tube morbidity. Pediatr Infect Dis J. 1995;14:1068 –1074
68. Bernard PA, Stenstrom RJ, Feldman W, Durieux-Smith A. Randomized,
controlled trial comparing long-term sulfonamide therapy to ventilation
tubes for otitis media with effusion. Pediatrics. 1991;88:215–222
69. Brook I, Gober AE. Prophylaxis with amoxicillin or sulfisoxazole for
otitis media: effect on the recovery of penicillin-resistant bacteria from
children. Clin Infect Dis. 1996;22:143–145
70. Klein JO. Lessons from recent studies on the epidemiology of otitis
media. Pediatr Infect Dis J. 1994;13:1031–1034
71. Niemela M, Uhari M, Mottonen M. A pacifier increases the risk of
recurrent acute otitis media in children in day care centers. Pediatrics.
1995;96:884 – 888
72. Heikkinen T, Ruuskanen O, Waris M, Ziegler T, Arola M, Halonen P.
Influenza vaccination in the prevention of acute otitis media in children
[see Comments]. Am J Dis Child. 1991;145:445– 448
73. Bluestone CD. Surgical management of otitis media: current indications
and role related to increasing bacterial resistance. Pediatr Infect Dis J.
1994;13:1058 –1063
74. Giebink GS. Immunology: promise of new vaccines. Pediatr Infect Dis J.
1994;13:1064 –1068
75. Alho OP, Laara E, Oja H. What is the natural history of recurrent acute
otitis media in infancy? J Fam Pract. 1996;43:258 –264
76. Bitar CN, Steele RW. Use of prophylactic antibiotics in children. Adv
Pediatr Infect Dis. 1995;10:227–262
macrolide-resistant group A streptococci. Pediatrics
1998;101:171–174; group A Streptococcus, pharyngitis,
diagnosis, antimicrobial therapy.
PRINCIPLES
1. Diagnosis of group A streptococcal pharyngitis
should be made based on results of appropriate
laboratory tests in conjunction with clinical and
epidemiologic findings.
2. Antimicrobial therapy should not be given to a
child with pharyngitis in the absence of diagnosed
group A streptococcal or other bacterial infection.
3. A penicillin remains the drug of choice for treat
ing group A streptococcal pharyngitis.
BACKGROUND AND JUSTIFICATION
S
ore throat is one of the most common com
plaints in pediatrics, resulting in millions of
physician office visits each year. Group A Strep
tococcus (S pyogenes), the leading bacterial cause of
pharyngitis, accounts for �15% of all cases.1 Diagno
sis and treatment of streptococcal pharyngitis are
important because antimicrobial therapy initiated
complications, lead to more rapid resolution of ill
SUPPLEMENT 171
 media. A double-blind crossover study in pediatric practice. N Engl
J Med. 1974;291:664 – 667
57. Schwartz RH, Puglise J, Rodriguez WJ. Sulphamethoxazole prophylaxis
in the otitis-prone child. Arch Dis Child. 1982;57:590 –593
58. Schuller DE. Prophylaxis of otitis media in asthmatic children. Pediatr
Infect Dis. 1983;2:280 –283
59. Liston TE, Foshee WS, Pierson WD. Sulfisoxazole chemoprophylaxis for
frequent otitis media. Pediatrics. 1983;71:524 –530
60. Varsano I, Volovitz B, Mimouni F. Sulfisoxazole prophylaxis of middle ear
effusion and recurrent acute otitis media. Am J Dis Child. 1985;139:632– 635
61. Gonzalez C, Arnold JE, Woody EA, et al. Prevention of recurrent acute
otitis media: chemoprophylaxis versus tympanostomy tubes. Laryngo
scope. 1986;96:1330 –1334
62. Paradise JL. Antimicrobial prophylaxis for recurrent acute otitis media.
Ann Otol Rhinol Laryngol. 1981;90(suppl):53–57
63. Goldstein NA, Sculerati N. Compliance with prophylactic antibiotics for
otitis media in a New York City clinic. Int J Pediatr Otorhinolaryngol.
1994;28:129 –140
64. Prellner K, Fogle-Hansson M, Jorgensen F, Kalm O, Kamme C. Prevention
of recurrent acute otitis media in otitis-prone children by intermittent
prophylaxis with penicillin. Acta Oto-Laryngologica. 1994;114:182–187
65. Heikkinen T, Ruuskanen O, Ziegler T, Waris M, Puhakka H. Short-term
use of amoxicillin-clavulanate during upper respiratory tract infection
for prevention of acute otitis media. J Pediatr. 1995;126:313–316
66. Berman S, Nuss R, Roark R, Huber-Navin C, Grose K, Herrera M.
Effectiveness of continuous vs. intermittent amoxicillin to prevent epi
sodes of otitis media. Pediatr Infect Dis J. 1992;11:63– 67
Pharyngitis—Principles of Judicious Use of Antimicrobial Agents
Benjamin Schwartz, MD*; S. Michael Marcy, MD‡; William R. Phillips, MD, MPH§;
Michael A. Gerber, MD�; and Scott F. Dowell, MD, MPH*
ABSTRACT. Accurate diagnosis of group A strepto
coccal pharyngitis and appropriate antimicrobial ther
apy are important, particularly to prevent nonsuppu
rative sequelae such as rheumatic fever. Most episodes
of sore throat, however, are caused by viral agents.
Clinical findings cannot reliably differentiate strepto
coccal from viral pharyngitis and most physicians tend
to overestimate the probability of a streptococcal in
fection based on history and physical examination
alone. Therefore, diagnosis should be based on results
of a throat culture or an antigen-detection test with
throat culture backup. Presumptively starting therapy
pending results of a culture is discouraged because
treatment often continues despite a negative test re
sult. Other bacterial causes of pharyngitis are uncom
mon and often can be diagnosed based on nonpharyn
geal findings. Penicillin remains the drug of choice for
streptococcal pharyngitis because of its effectiveness,
relatively narrow spectrum, and low cost. No group A
streptococci are resistant to �-lactam antibiotics. High
rates of resistance to macrolides has been documented
in several areas; in Finland, decreased national rates of
macrolide use led to a decline in the proportion of
From the *Childhood and Respiratory Diseases Branch, National Centers
for Infectious Diseases, Centers for Disease Control and Prevention,
Atlanta, Georgia; ‡Kaiser Permanente, Panorama City, California; §North
within 9 days of onset is effective in preventing acute
west Family Medicine, Seattle, Washington; and �Connecticut Children;s
rheumatic fever.2 In addition, treatment of group A
Medical Center, Hartford, Connecticut.
streptococcal infection may prevent suppurative
Reprint requests to (S.F.D.) Centers for Disease Control and Prevention,
Mailstop C-23, 1600 Clifton Rd, NE, Atlanta, GA 30333.
PEDIATRICS (ISSN 0031 4005). Copyright © 1998 by the American Acad
ness, and prevent the spread of infection. Neverthe
emy of Pediatrics.
less, because most episodes of sore throat are caused
67. Daly KA, Giebink GS, Lindgren B, et al. Randomized trial of the efficacy
of trimethoprim-sulfamethoxazole and prednisone in preventing post
tympanostomy tube morbidity. Pediatr Infect Dis J. 1995;14:1068 –1074
68. Bernard PA, Stenstrom RJ, Feldman W, Durieux-Smith A. Randomized,
controlled trial comparing long-term sulfonamide therapy to ventilation
tubes for otitis media with effusion. Pediatrics. 1991;88:215–222
69. Brook I, Gober AE. Prophylaxis with amoxicillin or sulfisoxazole for
otitis media: effect on the recovery of penicillin-resistant bacteria from
children. Clin Infect Dis. 1996;22:143–145
70. Klein JO. Lessons from recent studies on the epidemiology of otitis
media. Pediatr Infect Dis J. 1994;13:1031–1034
71. Niemela M, Uhari M, Mottonen M. A pacifier increases the risk of
recurrent acute otitis media in children in day care centers. Pediatrics.
1995;96:884 – 888
72. Heikkinen T, Ruuskanen O, Waris M, Ziegler T, Arola M, Halonen P.
Influenza vaccination in the prevention of acute otitis media in children
[see Comments]. Am J Dis Child. 1991;145:445– 448
73. Bluestone CD. Surgical management of otitis media: current indications
and role related to increasing bacterial resistance. Pediatr Infect Dis J.
1994;13:1058 –1063
74. Giebink GS. Immunology: promise of new vaccines. Pediatr Infect Dis J.
1994;13:1064 –1068
75. Alho OP, Laara E, Oja H. What is the natural history of recurrent acute
otitis media in infancy? J Fam Pract. 1996;43:258 –264
76. Bitar CN, Steele RW. Use of prophylactic antibiotics in children. Adv
Pediatr Infect Dis. 1995;10:227–262
macrolide-resistant group A streptococci. Pediatrics
1998;101:171–174; group A Streptococcus, pharyngitis,
diagnosis, antimicrobial therapy.
PRINCIPLES
1. Diagnosis of group A streptococcal pharyngitis
should be made based on results of appropriate
laboratory tests in conjunction with clinical and
epidemiologic findings.
2. Antimicrobial therapy should not be given to a
child with pharyngitis in the absence of diagnosed
group A streptococcal or other bacterial infection.
3. A penicillin remains the drug of choice for treat
ing group A streptococcal pharyngitis.
BACKGROUND AND JUSTIFICATION
S
ore throat is one of the most common com
plaints in pediatrics, resulting in millions of
physician office visits each year. Group A Strep
tococcus (S pyogenes), the leading bacterial cause of
pharyngitis, accounts for �15% of all cases.1 Diagno
sis and treatment of streptococcal pharyngitis are
important because antimicrobial therapy initiated
complications, lead to more rapid resolution of ill
SUPPLEMENT 171
 REFERENCES
1. McCaig LF, Hughes JM. Trends in antimicrobial drug prescribing
among office-based physicians in the United States. JAMA. 1995;273:
214 –219
2. Klein JO. Current issues in upper respiratory tract infections in infants
and children: rationale for antibacterial therapy. Pediatr Infect Dis J.
1994;13:S5–9
3. Paradise JL. On classifying otitis media as suppurative or nonsuppura
tive, with a suggested clinical schema. J Pediatr. 1987;111:948 –51
4. Stool SE, Berg AO, Berman S, et al. Otitis media with effusion in young
children. Clinical practice guideline. Agency for Health Care Policy and
Research Publication no 94-0622; 1994
5. Rosenfeld RM, Vertrees JE, Carr J, et al. Clinical efficacy of antimicrobial
drugs for acute otitis media: metaanalysis of 5400 children from thirty-
three randomized trials. J Pediatr. 1994;124:355–367
6. Kaleida PH, Casselbrant ML, Rockette HE, et al. Amoxicillin or myrin
gotomy or both for acute otitis media: results of a randomized clinical
trial. Pediatrics. 1991;87:466 – 474
7. Burke P, Bain J, Robinson D, Dunleavey J. Acute red ear in children:
controlled trial of non-antibiotic treatment in general practice. Br Med J.
1991;303:558 –562
8. Rosenfeld RM. What to expect from medical treatment of otitis media.
Pediatr Infect Dis J. 1995;14:731–738
9. Marchant CD, Carlin SA, Johnson CE, Shurin PA. Measuring the com
parative efficacy of antibacterial agents for acute otitis media: the “Pol
lyanna phenomenon.” J Pediatr. 1992;120:72–77
10. Hamrick HJ, Garfunkel JM. Therapy for acute otitis media: applicability
of metaanalysis to the individual patient. J Pediatr. 1994;124:431
11. Hayden GF. Acute suppurative otitis media in children. Diversity of
clinical diagnostic criteria. Clin.Pediatr. 1981;20:99 –104
12. Paradise JL. Managing otitis media: a time for change. Pediatrics. 1995;
96:712–715
13. Isaacson G. The natural history of a treated episode of acute otitis
media. Pediatrics. 1996;98:968 –971
14. Klein JO. Otitis media. Clin Infect Dis. 1994;19:823– 833
15. Weiss JC, Yates GR, Quinn LD. Acute otitis media: making an accurate
diagnosis. Am Fam Physician. 1996;53:1200 –1206
16. Baker RB. Is ear pulling associated with ear infection? Pediatrics. 1992;
90:1006 –1007
17. Schwartz RH, Rodriguez WJ, Brook I, Grundfast KM. The febrile re
sponse in acute otitis media. JAMA. 1981;245:2057–2058
18. Niemela M, Uhari M, Jounio-Ervasti K, Luotonen J, Alho OP, Vierimaa
E. Lack of specific symptomatology in children with acute otitis media.
Pediatr Infect Dis J. 1994;13:765–768
19. Arola M, Ruuskanen O, Ziegler T, et al. Clinical role of respiratory virus
infection in acute otitis media. Pediatrics. 1990;86:848 – 855
20. Green SM, Rothrock SG. Single-dose intramuscular ceftriaxone for acute
otitis media in children. Pediatrics. 1993;91:23–30
21. Charney E, Bynum R, Eldredge D, et al. How well do patients take oral
penicillin? A collaborative study in private practice. Pediatrics. 1967;40:
188 –195
22. Reed BD, Lutz LJ, Zazove P, Ratcliffe SD. Compliance with acute otitis
media treatment. J Fam Pract. 1984;19:627– 632
23. Chaput de Saintonge DM, Levine DF, Savage IT, et al. Trial of three-day
and ten-day courses of amoxycillin in otitis media. Br Med J. 1982;284:
1078 –1081
24. Meistrup-Larsen KI, Sorensen H, Johnsen NJ, Thomsen J, Mygind N,
Sederberg-Olsen J. Two versus seven days penicillin treatment for acute
otitis media. A placebo controlled trial in children. Acta Oto-
Laryngologica. 1983;96:99 –104
25. Bain J, Murphy E, Ross F. Acute otitis media: clinical course among
children who received a short course of high dose antibiotic. Br Med.
1985;291:1243–1246
26. Jones R, Bain J. Three-day and seven-day treatment in acute otitis
media: a double-blind antibiotic trial. J Roy Coll Gen Pract. 1986;36:
356 –358
27. Hendrickse WA, Kusmiesz H, Shelton S, Nelson JD. Five vs. ten days of
therapy for acute otitis media. Pediatr Infect Dis J. 1988;7:14 –23
28. Gooch WM III, Blair E, Puopolo A, et al. Effectiveness of five days of
therapy with cefuroxime axetil suspension for treatment of acute otitis
media. Pediatr Infect Dis J. 1996;15:157–164
29. Barnett ED, Teele DW, Klein JO, Cabral HJ, Kharasch SJ. Comparison
of ceftriaxone and trimethoprim-sulfamethoxazole for acute otitis
media. Greater Boston Otitis Media Study Group. Pediatrics. 1997;99:
23–28
30. Froom J, Culpepper L, Grob P, et al. Diagnosis and antibiotic treatment
170 SUPPLEMENT
of acute otitis media: report from International Primary Care Network.
Br Med J. 1990;300:582–586
31. Lundgren K, Ingvarsson L. Acute otitis media in Sweden. Role of
Branhamella catarrhalis and the rationale for choice of antimicrobial
therapy. Drugs. 1986;31(suppl)3:125–131
32. Gehanno P, Taillebe M, Denis P, et al. Short-course cefotaxime com
pared with five-day co-amoxyclav in acute otitis media in children.
J Antimicrob Chemother. 1990;26(suppl A):29 –36
33. Karma P, Palva T, Kouvalainen K, et al. Finnish approach to the treat
ment of acute otitis media. Report of the Finnish Consensus Conference.
Ann Otol Rhinol Laryngol. 1987;129(suppl):1–19
34. van Buchem FL, Peeters MF, van’t Hof MA. Acute otitis media: a new
treatment strategy. Br Med J. 1985;290:1033–1037
35. Carlin SA, Marchant CD, Shurin PA, Johnson CE, Super DM, Rehmus
JM. Host factors and early therapeutic response in acute otitis media.
J Pediatr. 1991;118:178 –183
36. Hathaway TJ, Katz HP, Dershewitz RA, Marx TJ. Acute otitis media:
who needs posttreatment follow-up? Pediatrics. 1994;94:143–147
37. Harsten G, Prellner K, Heldrup J, Kalm O, Kornfalt R. Treatment failure
in acute otitis media. A clinical study of children during their first three
years of life. Acta Oto-Laryngologica. 1989;108:253–258
38. Hoberman A, Paradise JL, Burch DJ, et al. Equivalent efficacy and
reduced occurrence of diarrhea from a new formulation of amoxicillin/
clavulanate potassium (Augmentin) for treatment of acute otitis media
in children. Pediatr Infect Dis J. 1997;16:463– 470
39. Rosenfeld RM, Post JC. Meta-analysis of antibiotics for the treatment
of otitis media with effusion. Otolaryngol Head Neck Surg. 1992;106:
378 –386
40. Williams RL, Chalmers TC, Stange KC, Chalmers FT, Bowlin SJ. Use of
antibiotics in preventing recurrent acute otitis media and in treating
otitis media with effusion. A meta-analytic attempt to resolve the brou
haha. JAMA. 1993;270:1344 –1351
41. Zielhuis GA, Straatman H, Rach GH, van den Broek P. Analysis and
presentation of data on the natural course of otitis media with effusion
in children. Int J Epidemiol. 1990;19:1037–1044
42. Wald ER. Otitis media and sinusitis: a clinical update. Clin Updates
Pediatr Infect Dis. 1995;1:1– 4
43. Dowell SF, Schwartz B. Resistant pneumococci: protecting patients
through judicious use of antibiotics. Am Fam Physician. 1997;55:
1647–1654
44. Block SL, Harrison CJ, Hedrick JA, et al. Penicillin-resistant Streptococcus
pneumoniae in acute otitis media: risk factors, susceptibility patterns and
antimicrobial management. Pediatr Infect Dis J. 1995;14:751–759
45. Reichler MR, Allphin AA, Breiman RF, et al. The spread of multiply
resistant Streptococcus pneumoniae at a day care center in Ohio. J Infect
Dis. 1992;166:1346 –1353
46. Teele DW, Klein JO, Chase C, Menyuk P, Rosner BA. Otitis media in
infancy and intellectual ability, school achievement, speech, and lan
guage at age 7 years. Greater Boston Otitis Media Study Group. J Infect
Dis. 1990;162:685–94
47. Baldwin CD, Owen MJ, Johnson DL, et al. Effects of early otitis media
with effusion (OME) on cognitive development at 3 and 5 years. Pre
sented at the Meeting of the Pediatric Academic Society; May 1996;
Washington, DC
48. Roberts JE, Burchinal MR, Clarke-Klein SM. Otitis media in early child
hood and cognitive, academic, and behavior outcomes at 12 years of
age. J Pediatr Psychol. 1995;20:645– 660
49. Teele DW, Klein JO, Rosner BA. Epidemiology of otitis media in chil
dren. Ann Otol Rhinol Laryngol. 1980;89(suppl):5– 6
50. Schwartz RH, Rodriguez WJ, Hayden GF, Grundfast KM. The reeval
uation visit for acute otitis media. J Fam Pract. 1987;24:145–148
51. Klein JO. Preventing recurrent otitis: what role for antibiotics? Contemp
Pediatr. 1994;11:44 – 60
52. Lampe RM, Weir MR. Erythromycin prophylaxis for recurrent otitis
media. Clin Pediatr. 1986;25:510 –515
53. Principi N, Marchisio P, Massironi E, Grasso RM, Filiberti G. Prophy
laxis of recurrent acute otitis media and middle-ear effusion. Compar
ison of amoxicillin with sulfamethoxazole and trimethoprim. Am J Dis
Child. 1989;143:1414 –1418
54. Casselbrant ML, Kaleida PH, Rockette HE, et al. Efficacy of antimicro
bial prophylaxis and of tympanostomy tube insertion for prevention of
recurrent acute otitis media: results of a randomized clinical trial. Pedi
atr Infect Dis J. 1992;11:278 –286
55. Gaskins JD, Holt RJ, Kyong CU, Weart CW, Ward J. Chemoprophylaxis
of recurrent otitis media using trimethoprim/sulfamethoxazole. Drug
Intell Clin Pharm. 1982;16:387–390
56. Perrin JM, Charney E, MacWhinney JB Jr, McInerny TK, Miller RL,
Nazarian LF. Sulfisoxazole as chemoprophylaxis for recurrent otitis
Antibiotic Prophylaxis Should Be Reserved for Control
of Recurrent AOM
The efficacy of continuous prophylactic antimicro
bials for the control of recurrent AOM is well-estab
lished, although the decrease in frequency of recur
rent episodes is small.40 Nevertheless, because of the
potential consequences of emergence of additional
resistant pneumococci, a recommendation that anti
biotic prophylaxis for AOM be avoided whenever
possible has been made.12 Others have argued that
prophylaxis remains a valuable therapeutic option
for children with recurrent AOM and should not be
dismissed so readily.51
Trials in which children treated with daily low-dose
antibiotic therapy were compared with those given
placebo have consistently documented a lower inci
dence of AOM in the treated group, whether the anti
biotic used was erythromycin,52 amoxicillin,53,54 tri
methoprim-sulfamethoxazole,53,55 or sulfisoxazole.56 – 61
A metaanalysis summarizing these results concluded
that antibiotic treatment resulted in an average de
crease in the number of episodes of AOM of 0.11 epi
sode per patient per month, or slightly more than one
episode per year.40 The treatment effect tended to be
greater when sulfisoxazole was used, when treatment
was continued for �6 months, or when the population
studied had a high rate of recurrences.40
This last point is important because it indicates
that the type of patient selected for prophylaxis will
determine the utility of the prophylactic regimen.
The benefit of prophylaxis will be greatest if strict
criteria for initiating prophylaxis are used and its use
limited to those who are likely to have frequent
recurrences. The most consistent criterion for pro
phylaxis in the published trials has been three or
more distinct and well-documented episodes of
AOM in the preceding 6 months or four episodes in
the preceding year. Patients at high risk for severe or
recurrent disease who are most likely to benefit from
prophylaxis include those �2 years of age, those in
out-of-home child care, and Native American chil
dren.51,62 On the other hand, some otherwise eligible
children may be poor candidates for prophylaxis
because of their decreased likelihood of compliance
with the regimen, which was �50% in one inner-city
population.63
Alternative approaches to antimicrobial prophy
laxis for otitis media using different schedules have
been attempted, but none have been as consistently
beneficial as continuous prophylaxis as outlined
above. Intermittent prophylaxis using antimicrobials
administered at the onset of signs of upper respira
tory infection was found to be beneficial in prevent
ing recurrent AOM in one study,64 but not another,65
and was significantly less effective than continuous
prophylaxis when the two methods were com
pared.66 Prophylactic trimethoprim-sulfamethox
azole in conjunction with prednisone after tympa
nostomy tube insertion decreased the short-term rate
of tube extrusion, but there was no beneficial effect
on the rate of AOM recurrence and no overall long-
term benefit.67 An attempt at antibiotic prophylaxis
rather than tympanostomy tube insertion has been
advocated in one study of children with long-
standing OME and hearing loss, but surgically
treated patients had a lower rate of treatment
failure and better short-term hearing than those on
prophylaxis.68
The benefit of any form of prophylactic therapy
must be weighed against the risk of promoting anti
biotic resistance. Evidence that even short courses of
antimicrobial therapy are associated with an in
creased risk of nasopharyngeal carriage as well as of
invasive disease with resistant bacteria has been re
viewed above and elsewhere.43 In addition, there is
specific evidence that antibiotic prophylaxis in
creases the likelihood of nasopharyngeal coloniza
tion with resistant pneumococci45,69 and the pro
portion of children with �-lactamase-producing
organisms in middle ear effusions.54,69 This effect is
seen among children given amoxicillin prophylaxis,
but not among those given sulfisoxazole.69 Impor
tantly, the rate of colonization with resistant strains
returned to baseline levels several months after pro
phylaxis was discontinued.69
Other interventions that may decrease the inci
dence of recurrent AOM without the risks of antibi
otic prophylaxis include eliminating smoking in the
home,70 reducing day care attendance,70 eliminating
pacifiers,71 and giving influenza vaccine.72 Insertion
of tympanostomy tubes has been demonstrated to be
an effective means of reducing the frequency of re
current AOM and may be a reasonable alternative to
antimicrobial prophylaxis in selected children.73
Conjugate pneumococcal vaccines may provide an
important alternative in the future.74 Parents should
also be reassured that the incidence of recurrent
AOM appears to decrease with increasing age of the
child.75
Control of recurrent AOM among children with
three or more well-documented and separate epi
sodes in the preceding 6 months or four or more
episodes in the preceding 12 months is the only
indication for which evidence of the beneficial effects
of antibiotic prophylaxis has been consistent and
persuasive. Because of the potential consequences of
promoting resistant bacteria to both the patient and
the community, prophylaxis should not be initiated
for other indications. When initiated, the duration of
prophylactic therapy should be no more than 6
months, because longer courses are less effective and
may be more likely to promote colonization with
resistant bacteria.40,76 Either sulfisoxazole or amoxi
cillin is the agent of choice; cephalosporins have not
been demonstrated to be effective. Sulfisoxazole has
been used in the majority of controlled trials of pro
phylaxis, appears to be more efficacious at prevent
ing recurrences than the other agents, and may be
less likely than amoxicillin to promote colonization
with �-lactamase-producing bacteria or resistant
pneumococci.
ACKNOWLEDGMENTS
We thank Drs Jerome O. Klein, Jack L. Paradise, Leah Raye
Mabry, and Doug Long and members of the Committee on Infec
tious Diseases of the American Academy of Pediatrics for their
careful review of this paper.
SUPPLEMENT 169
Antimicrobials Are Not Indicated for Initial Treatment
of OME
Recent comprehensive reviews of the literature
have been conducted and an expert panel of the US
AHCPR has addressed the issue of antibiotic treat
ment for OME. Results of these analyses indicate that
in the majority of cases, antimicrobial therapy can be
deferred safely while OME resolves spontaneously,
and that antimicrobials are effective at resolving ef
fusion in only a minority of cases.
Three metaanalyses of published trials of antibiotic
therapy for OME have concluded that there is a small
but statistically significant effect on short-term reso
lution.4,39,40 Most of these trials enrolled children with
documented middle ear effusion but no recent his
tory of AOM. No beneficial effect of therapy was
seen in those studies that included children with
illnesses characterized by a high natural cure rate,
such as children with effusion after a recent episode
of AOM.39 Approximately 65% of all cases of OME
will resolve within 3 months without antibiotic ther
apy,41 as will 90% of the subset of OME that imme
diately follows a diagnosed episode of AOM. Al
though the overall difference in the rate of short-term
resolution between treated and untreated children in
the metaanalyses was statistically significant, about
seven children would have to be treated with anti
microbials for one to benefit.8 Of greater importance,
however, is that there was no significant difference in
the incidence of OME when assessed �1 month after
treatment was completed, whether placebo or anti
biotic therapy was used.40 These findings have
prompted many experts to recommend that middle
ear effusion in the absence of AOM should not be
treated with antimicrobials at all.42
Guidelines for the diagnosis and treatment of
OME have been published recently by an expert
panel convened by the US AHCPR and endorsed by
the American Academy of Pediatrics, the American
Academy of Family Physicians, and the American
Academy of Otolaryngology–Head and Neck Sur
gery.4 For initial treatment of OME, the panel en
dorsed either of two options with similar long-term
outcomes: observation with no therapy or antibiotic
therapy.
With the accumulation of evidence that antibiotic
use increases the risk for both colonization and in
vasive disease with penicillin-resistant Streptococcus
pneumoniae,43 observation without antibiotic therapy
now appears to be the preferred option. For the
practicing physician faced with a well-appearing
child with a middle ear effusion, considerations of
risks and benefits to that individual child appropri
ately outweigh concerns about the emergence of an
timicrobial resistance in the community as a whole.
Thus, the observation that children treated with a
course of antimicrobials are at increased risk to be
come carriers of nonsusceptible pneumococci as a
result of that treatment,44 and that carriers of resis
tant strains are more likely to fail antibiotic therapy,45
must take precedence over the sometimes marginal
benefits of antibiotic therapy for that child.
The AHCPR guidelines recommend antibiotic
168 SUPPLEMENT
therapy or bilateral myringotomy with insertion of
tympanotomy tubes for patients in whom bilateral
effusion has been documented to persist for 3
months and is accompanied by significant bilateral
hearing loss. This approach is reasonable, because
persistent middle ear effusions in infancy have been
associated in some studies with deficits in cognitive
function and school achievement at age 7 years,46
although this has not been a consistent finding,4 and
recent evidence indicates that cognitive deficits, if
present, may be related more to diminished maternal
responsiveness secondary to the hearing loss than to
the hearing loss per se.47,48
The AHCPR panel defined a patient with OME as
a child between 1 and 3 years of age with effusion
present 6 weeks after an acute episode of otitis me
dia, with no apparent symptoms, and with no un
derlying medical condition. The panel estimated that
25% to 35% of all diagnoses of otitis media would fit
the criteria of OME.4 Were antimicrobials deferred
for this group of children alone, 6 to 8 million courses
of unnecessary antibiotic therapy could be avoided
each year.
Persistent Middle Ear Effusion After Therapy for AOM
Is Expected and Does Not Require Retreatment
The natural history of appropriately treated AOM
is for middle ear effusion to persist for weeks to
months, a fact that may not be recognized clearly by
physicians who reexamine ears soon after therapy is
completed. Approximately 70% of children will have
fluid in the middle ear at 2 weeks, 50% at 1 month,
20% at 2 months, and 10% at 3 months, despite
appropriate antibiotic therapy.14,42,49 Thus, when mid
dle ear fluid is detected in asymptomatic children at
follow-up visits for AOM, administering additional
courses of antimicrobials is generally unnecessary.50
An important step in reducing the burden of unnec
essary antibiotic treatment for otitis media is the
recognition that persistent effusions are part of
the expected course of AOM and do not warrant
therapy.
It may appear difficult to distinguish the child who
has a persistent middle ear effusion as part of the
natural course of appropriately treated AOM from
the child who has a new effusion as part of a second
episode of acute disease, but this distinction can be
made by using the same criteria listed above to dis
tinguish AOM from OME. When the effusion is ac
companied by new onset of local or systemic signs or
symptoms of infection, such as fever or persistent ear
pain, AOM is diagnosed and a course of antimicro
bials is administered. On the other hand, middle ear
effusion in a child who has had an episode of AOM
in the previous 2 to 3 months and in whom signs of
acute illness are absent or nonspecific, such as rhi
norrhea alone, would not warrant a second course of
antimicrobials. Irrespective of the recent history of
middle ear disease, the administration of a course of
antimicrobials should be recommended only for
those children with both middle ear effusion and
new onset of local or systemic illness, or with bilat
eral effusions accompanied by documented hearing
loss for �3 months, as discussed above.
establishing the presence of middle ear effusion,
without which the diagnosis of AOM cannot be sup
ported.4,12 (In rare circumstances, the practitioner
may observe signs of acute inflammation in the
hours before fluid accumulates in the middle ear
cavity.13) Pneumatic otoscopy should be used to as
sess four principal characteristics of the tympanic
membrane: position, color, translucency, and mobil
ity.14 The use of visual otoscopy alone is discouraged
because of the inability to assess the mobility of the
tympanic membrane.4 Newer diagnostic tools such
as tympanometry and acoustic reflectometry can aid
in establishing the presence of fluid and in validating
the examiner’s skills through repeated use and com
parison with visual observation.
Agreement may be more difficult on which signs
and symptoms of acute local or systemic illness are
sufficient to establish the diagnosis of AOM in con
junction with middle ear effusion. The diagnosis can
be established by the presence of local signs such as
otorrhea with evidence of middle ear origin, a bulg
ing tympanic membrane that has cloudy or yellow
fluid visible behind it or is distinctly red, or local
symptoms such as ear pain.15 Ear-pulling in the ab
sence of other symptoms is not necessarily attribut
able to AOM.16 Fever may be indicative of AOM,
although in the absence of any other findings, such
as ear pain or a red or bulging tympanic membrane,
fever often may be unrelated to middle ear effusion.17
Other signs and symptoms such as rhinorrhea,
cough, irritability, headache, anorexia, vomiting, or
diarrhea may be present but are not specific for
AOM.18 Although viral upper respiratory infections
frequently precede or accompany AOM, the pres
ence of rhinorrhea or other nonspecific signs or
symptoms of upper respiratory infection alone is not
adequate to differentiate AOM from OME. These
nonspecific symptoms usually reflect an underlying
or preceding viral illness and do not resolve as rap
idly after appropriate antibiotic therapy as do fever
and ear pain.19
Uncomplicated AOM May Be Treated With a 5- to
7-Day Course of Antimicrobials in Certain Patients
In the United States, AOM traditionally has been
treated with a 10-day course of antimicrobials. There
are few controlled data to support such a practice,
which seems to have been carried over from the
recommendations for 10 days of penicillin for strep
tococcal pharyngitis.20 Although physicians pre
scribe 10-day courses, children often fail to complete
them.21,22
A number of randomized trials have compared
shorter courses of antimicrobial therapy, ranging
from 2 to 7 days, with more traditional courses and
have reported satisfactory results.23–27 Most of the
trials were conducted in Europe, where differences
in standard care are such that the results may not be
easily applicable in the United States. One compari
son was of 2 days versus 7 days of penicillin V, an
antibiotic not often recommended or used to treat
AOM in the United States.24 Two of the trials en
rolled only children �3 years of age, although most
antibiotic failures are reported in those �18
months.25,26 A trial from the United States reported
no difference in outcome among 59 children who
received 5 days of cefaclor (90% success) compared
with 64 who received 10 days of cefaclor (92% suc
cess).27 However, this study, like those cited previ
ously, may not have had the statistical power to
detect a clinically significant difference. A recent trial
including 719 patients reported that the efficacy of 5
days of cefuroxime axetil was equivalent to 10 days
of either cefuroxime or amoxicillin/clavulanate.28
Perhaps more persuasive are reports that a single
dose of ceftriaxone, which produces therapeutic mid
dle ear concentrations of antibiotic for only 3 to 5
days, is equally effective as a 10-day course of amoxi
cillin or trimethoprim-sulfamethoxazole.20,29 In any
case, although the evidence to support shorter
courses of antimicrobials is not optimal, the evidence
to support 10 to 14 days of antimicrobials is practi
cally nonexistent. In parts of Europe, deferring anti
biotic therapy unless symptoms persist for �2 days
or treating with 5 to 7 days of antimicrobials is the
standard of care, and cure rates between 66% and
92% have been recorded among children treated only
with analgesics and observation.6,30 –34
Certainly, there are theoretic advantages to de
creasing the duration of therapy to 5 to 7 days for
uncomplicated AOM. One would anticipate a reduc
tion in selective pressure favoring resistant organ
isms, both in the community and in the individual
patient. In fact, shorter courses may reflect more
realistically the actual dispensing practices of parents
and make it more likely that the medications are
given as prescribed.
Although the available data support the use of
short-course therapy for older children with mild
AOM, such treatment has not been well-evaluated in
children with severe or complicated AOM. Ten or
more days of antimicrobials may be necessary for
those children who present with perforation of the
tympanic membrane.27 In addition, the trials assess
ing efficacy of shorter courses generally excluded
patients at higher risk for treatment failure, such as
those with underlying medical conditions and those
with chronic or recurrent otitis media.35 Data sup
porting short courses of therapy in such patients are
therefore lacking, and short-course therapy for these
patients cannot be recommended until more data
become available.
Short-course therapy also may not be appropriate
for younger children. Children �15 months to 2
years of age are at increased risk for treatment fail
ure, even with conventional dosing.35–37 The eight
trials of short-course therapy reviewed above en
rolled �250 children �18 months of age, but most
did not analyze the success of therapy separately for
this group. Recently, a randomized trial comparing 5
days with 10 days of amoxicillin/clavulanate docu
mented significant differences favoring the 10-day
regimen among children �2 years of age.38 In the
absence of additional data testing the efficacy of
short course treatment in this age group, it seems
prudent to restrict short-course therapy to children
�2 years of age.
SUPPLEMENT 167
plish this goal, and will avoid up to 8 million unneces
sary courses of antibiotics annually. Criteria for defining
these conditions are presented, as well as the evidence
supporting deferring antibiotic treatment. Discussions of
shortened courses of antibiotics for AOM and restricted
indications for antimicrobial prophylaxis are also pre
sented. Pediatrics 1998;101:165–171; antimicrobial resis
tance, antimicrobial use, otitis media, upper respiratory
infection, antimicrobial therapy, pediatrics, acute otitis
media, otitis media with effusion, prophylaxis.
ABBREVIATION. AHCPR, Agency for Health Care Policy and
Research.
PRINCIPLES
1. Episodes of otitis media should be classified as
acute otitis media (AOM) or otitis media with
effusion (OME).
2. Antimicrobials are indicated for treatment of
AOM; however, diagnosis requires documented
middle ear effusion and signs or symptoms of
acute local or systemic illness.
3. Uncomplicated AOM may be treated with a 5- to
7-day course of antimicrobials in certain patients.
4. Antimicrobials are not indicated for initial treat
ment of OME; treatment may be indicated if effu
sions persist for �3 months.
5. Persistent middle ear effusion (OME) after ther
apy for AOM is expected and does not require
retreatment.
6. Antimicrobial prophylaxis should be reserved for
control of recurrent AOM, defined by �3 distinct
and well-documented episodes/6 months or �4
episodes/12 months.
BACKGROUND AND JUSTIFICATION
O
titis media consistently leads the list of the
most common indications for outpatient an
timicrobial use in the United States.1 In recent
years, the number of office visits for otitis media has
increased out of proportion to the increase in popu
lation size, from 9.9 million visits in 1975 to 24.5
million in 1990. It is not clear why the diagnosis is
being made so much more often, although some
authorities have suggested an association with in
creased use of out-of-home child care.2
Because of its importance as an indication for an
tibiotic use, efforts to influence antibiotic prescribing
practices have consistently begun by addressing oti
tis media. As a result of this emphasis, there is a
considerable body of literature on which recommen
dations can be based. The relative efficacy of antibi
otic treatment for AOM and OME has been well-
defined, the natural history of appropriately treated
AOM is understood to include persistent middle ear
effusions for several weeks in the majority of chil
dren, and the indications for prophylaxis have been
evaluated. Yet children continue to routinely receive
antimicrobials for OME detected as an incidental
finding, for asymptomatic effusions detected only a
few weeks after an uncomplicated episode of AOM,
and in prophylactic regimens initiated in patients
who have not met strict criteria. More work is
needed to bring current antibiotic prescribing prac
166 SUPPLEMENT
tices in line with indications available from the con
siderable body of recent literature on otitis media.
The following guidelines are intended to begin this
process by highlighting situations in which antibiotic
use may be reduced without compromising patient
care.
EVIDENCE SUPPORTING PRINCIPLES
Episodes of Otitis Media Should Be Classified as AOM
or OME
Distinguishing each episode of otitis media in this
manner leads directly to a management strategy that
optimizes treatment for those children who require
it, but curtails the use of antimicrobials for children
in whom they would not be beneficial. The distinc
tion between these entities is usually clear, but clas
sification of some patients with equivocal otoscopic
findings may require careful clinical judgment.3
AOM is defined as the presence of fluid in the
middle ear in association with signs or symptoms of
acute local or systemic illness. Accompanying signs
and symptoms may be specific for AOM, such as
otalgia or otorrhea; or nonspecific, such as fever.
Antimicrobial agents are indicated for this condition,
as discussed below.
OME is defined as the presence of fluid in the
middle ear in the absence of signs or symptoms of
acute infection. Antimicrobials may be appropriately
deferred for this group of children, in agreement
with recommendations of an expert panel convened
by the US Agency for Health Care Policy and Re
search (AHCPR).4
Antimicrobials Are Indicated for Treatment of AOM
The cumulative evidence from randomized con
trolled trials in which antibiotic therapy has been
compared with no therapy for AOM is persuasive in
favoring antibiotic therapy, although the treatment
effect is small.5–7 Approximately 80% of untreated
children have clinical resolution by 7 to 14 days,
compared with �95% of those treated with antimi
crobials.5 Differences among the various antimicro
bials in terms of clinical efficacy, if present, are gen
erally too small to be detected. The benefit of
antimicrobial treatment is most apparent when
pathogenic bacteria are isolated from middle ear
fluid, when bacterial eradication is used to assess
outcome, or when clinical outcome was assessed at 2
to 3 days, rather than 7 to 14 days.6,8 –10
Diagnosis of AOM
Although there is general agreement that antimi
crobials are indicated for AOM, there is no such
agreement on how to establish the diagnosis. Specific
criteria for the diagnosis have been notoriously dif
ficult to validate or standardize, perhaps reflecting
the diversity of criteria used in practice and in clin
ical trials. For example, a survey of 165 pediatricians
reported 147 different sets of criteria for the diagno
sis of AOM.11 Furthermore, in clinical trials in which
standardization is even more essential, 18 different
sets of criteria were used in 26 trials.11
Agreement can be reached on the essential steps in
nying documents are a first step toward accomplish
ing this objective.
ACKNOWLEDGMENTS
We thank the members of the Committee on Infectious Diseases
of the American Academy of Pediatrics and Drs Leah Raye Mabry
and Doug Long for their careful reviews of this document.
REFERENCES
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antimicrobial era. Science. 1992;257:1050 –1055
3. Barnett ED, Klein JO. The problem of resistant bacteria for the manage
ment of acute otitis media. Pediatr Clin North Am. 1995;42:509 –517
4. Hofmann J, Cetron MS, Farley MM, et al. The prevalence of drug-
resistant Streptococcus pneumoniae in Atlanta. N Engl J Med. 1995;333:
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17. Ford KL, Mason EO Jr, Kaplan SL, Lamberth LB, Tillman J. Factors
associated with middle ear isolates of Streptococcus pneumoniae resistant
Otitis Media—Principles of Judicious Use of Antimicrobial Agents
Scott F. Dowell, MD, MPH*; S. Michael Marcy, MD‡; William R. Phillips, MD, MPH§;
Michael A. Gerber, MD�; and Benjamin Schwartz, MD*
From the *Childhood and Respiratory Diseases Branch, National Center for
ABSTRACT. Otitis media is the leading indication for
Infectious Diseases, Centers for Disease Control and Prevention, Atlanta,
outpatient antimicrobial use in the United States. Over-
Georgia; ‡Kaiser Permanente, Panorama City, California; §Northwest Fam
ily Medicine, Seattle, Washington; and �Connecticut Children’s Medical
Center, Hartford, Connecticut.
Received for publication Aug 8, 1997; accepted Sep 11, 1997.
Reprint requests to (S.F.D.) Centers for Disease Control and Prevention,
is to identify the subset of patients who are unlikely to
Mailstop C-23, 1600 Clifton Rd, NE, Atlanta, GA 30333.
benefit from antibiotics. Conscientiously distinguishing
PEDIATRICS (ISSN 0031 4005). Copyright © 1998 by the American Acad
acute otitis media (AOM) from otitis media with effusion
emy of Pediatrics.
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SUPPLEMENT 165
 Principles of Judicious Use of Antimicrobial Agents for Pediatric Upper

Respiratory Tract Infections

Scott F. Dowell, S. Michael Marcy, William R. Phillips, Michael A. Gerber and

Benjamin Schwartz

Pediatrics 1998;101;163-165

DOI: 10.1542/peds.101.1.S1.163

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nying documents are a first step toward accomplish
ing this objective.
ACKNOWLEDGMENTS
We thank the members of the Committee on Infectious Diseases
of the American Academy of Pediatrics and Drs Leah Raye Mabry
and Doug Long for their careful reviews of this document.
REFERENCES
1. McCaig LF, Hughes JM. Trends in antimicrobial drug prescribing
among office-based physicians in the United States. JAMA. 1995;273:
214 –219
2. Cohen ML. Epidemiology of drug resistance: implications for a post-
antimicrobial era. Science. 1992;257:1050 –1055
3. Barnett ED, Klein JO. The problem of resistant bacteria for the manage
ment of acute otitis media. Pediatr Clin North Am. 1995;42:509 –517
4. Hofmann J, Cetron MS, Farley MM, et al. The prevalence of drug-
resistant Streptococcus pneumoniae in Atlanta. N Engl J Med. 1995;333:
481– 486
5. Anonymous. Report of the ASM task force on antibiotic resistance.
Antimicrob Agents Chemother. 1995;39(suppl):1–23
6. Jernigan DB, Cetron MS, Breiman RF. Minimizing the impact of drug-
resistant Streptococcus pneumoniae (DRSP): a strategy from the DRSP
working group. JAMA. 1996;275:206 –209
7. O’Brien TF. The global epidemic nature of antimicrobial resistance and
the need to monitor and manage it locally. Clin Infect Dis. 1997;
24(suppl):S2– 8
8. McGowan JE Jr. Antimicrobial resistance in hospital organisms and its
relation to antibiotic use. Rev Infect Dis. 1983;5:1033–1048
9. Reichler MR, Allphin AA, Breiman RF, et al. The spread of multiply
resistant Streptococcus pneumoniae at a day care center in Ohio. J Infect
Dis. 1992;166:1346 –1353
10. Dowell SF, Schwartz B. Resistant pneumococci: protecting patients
through judicious use of antibiotics. Am Fam Physician. 1997;55:
1647–1654
11. Radetsky MS, Istre GR, Johansen TL, et al. Multiply resistant pneumo
coccus causing meningitis: its epidemiology within a day-care centre.
Lancet. 1981;2:771–773
12. Robins-Browne RM, Kharsany ABM, Koornhof HJ. Antibiotic-resistant
pneumococci in hospitalized children. J Hyg. 1984;93:9 –16
13. Duchin JS, Breiman RF, Diamond A, et al. High prevalence of multi-
drug-resistant Streptococcus pneumoniae among children in a rural
Kentucky community. Pediatr Infect Dis J. 1995;14:745–750
14. Zenni MK, Cheatham SH, Thompson JM, et al. Streptococcus pneumoniae
colonization in the young child: association with otitis media and re
sistance to penicillin. J Pediatr. 1995;127:533–537
15. Jackson MA, Shelton S, Nelson JD, McCracken GH Jr. Relatively peni
cillin-resistant pneumococcal infections in pediatric patients. Pediatr
Infect Dis J. 1984;3:129 –132
16. Pallares R, Gudiol F, Linares J, et al. Risk factors and response to
antibiotic therapy in adults with bacteremic pneumonia caused by
penicillin-resistant pneumococci. N Engl J Med. 1987;317:18 –22
17. Ford KL, Mason EO Jr, Kaplan SL, Lamberth LB, Tillman J. Factors
associated with middle ear isolates of Streptococcus pneumoniae resistant
Otitis Media—Principles of Judicious Use of Antimicrobial Agents
Scott F. Dowell, MD, MPH*; S. Michael Marcy, MD‡; William R. Phillips, MD, MPH§;
Michael A. Gerber, MD�; and Benjamin Schwartz, MD*
From the *Childhood and Respiratory Diseases Branch, National Center for
Infectious Diseases, Centers for Disease Control and Prevention, Atlanta,
Georgia; ‡Kaiser Permanente, Panorama City, California; §Northwest Fam-
ily Medicine, Seattle, Washington; and �Connecticut Children’s Medical
Center, Hartford, Connecticut.
Received for publication Aug 8, 1997; accepted Sep 11, 1997.
Reprint requests to (S.F.D.) Centers for Disease Control and Prevention,
Mailstop C-23, 1600 Clifton Rd, NE, Atlanta, GA 30333.
PEDIATRICS (ISSN 0031 4005). Copyright © 1998 by the American Acad-
emy of Pediatrics.
Downloaded from www.pediatrics.org by on July 12, 2005
to penicillin in a children’s hospital. J Pediatr. 1991;119:941–944
18. Tan TQ, Mason EO Jr, Kaplan SL. Penicillin-resistant systemic pneumo
coccal infections in children: a retrospective case– control study. Pediat
rics. 1993;92:761–767
19. Nava JM, Bella F, Garau J, et al. Predictive factors for invasive disease
due to penicillin-resistant Streptococcus pneumoniae: a population-based
study. Clin Infect Dis. 1994;19:884 – 890
20. Block SL, Harrison CJ, Hedrick JA, et al. Penicillin-resistant Streptococcus
pneumoniae in acute otitis media: risk factors, susceptibility patterns and
antimicrobial management. Pediatr Infect Dis J. 1995;14:751–759
21. Moreno F, Crisp C, Jorgensen JH, Patterson JE. The clinical and molec
ular epidemiology of bacteremias at a university hospital caused by
pneumococci not susceptible to penicillin. J Infect Dis. 1995;172:427– 432
22. Brook I, Gober AE. Prophylaxis with amoxicillin or sulfisoxazole for
otitis media: effect on the recovery of penicillin-resistant bacteria from
children. Clin Infect Dis. 1996;22:143–145
23. Worrall G, Chaulk P. Hope or experience? Clinical practice guidelines in
family practice. J Fam Pract. 1996;42:353–356
24. Paradise JL. Managing otitis media: a time for change. Pediatrics. 1995;
96:712–715
25. Goldman DA, Weinstein RA, Wenzel RP, et al. Strategies to prevent and
control the emergence and spread of antimicrobial-resistant microor
ganisms in hospitals: a challenge to hospital leadership. JAMA. 1996;
275:234 –240
26. Grimshaw JM, Russell IT. Effect of clinical guidelines on medical
practice: a systematic review of rigorous evaluations. Lancet. 1993;342:
317–322
27. Mainous AG III, Hueston WJ, Clak JR. Antibiotics and upper respira
tory infection: do some folks think there is a cure for the common cold?
J Fam Pract. 1996;42:357–361
28. Barden LS, Dowell SF, Schwartz B, Lackey C. Current attitudes regard
ing antibiotic use: results from physicians’ and parents’ focus group
discussions. International Conference on Acute Respiratory Infections;
July 1997; Canberra, Australia. Abstract. Page 77
29. Hamm RM, Hicks RJ, Bemben DA. Antibiotics and respiratory
infections: are patients more satisfied when expectations are met? J Fam
Pract. 1996;43:56 – 62
30. Schwartz B, Bell DM, Hughes JM. Preventing the emergence of antimi
crobial resistance: a call for action by clinicians, public health officials,
and parents. JAMA. 1997;278:944 –945
31. Fujita K, Murono K, Yoshikawa M, Murai T. Decline of erythromycin
resistance of group A streptococci in Japan. Pediatr Infect Dis J. 1994;13:
1075–1078
32. Baquero F, Martinez-Beltran J, Loza E. A review of antibiotic resistance
patterns of Streptococcus pneumoniae in Europe. J Antimicrob Chemother.
1991;28(suppl C):31–38
33. Arason VA, Kristinsson KG, Sigurdsson JA, Stefansdottir G, Molstad S,
Gudmundsson S. Do antimicrobials increase the carriage rate of peni
cillin resistant pneumococci in children? Cross-sectional prevalence
study. Br Med J. 1996;313:387–391
34. Boken DJ, Chartrand SA, Goering RV, Kruger R, Harrison CJ. Coloni
zation with penicillin-resistant Streptococcus pneumoniae in a child-care
center. Pediatr Infect Dis J. 1995;14:879 – 884
35. Stephenson J. Icelandic researchers are showing the way to bring down
rates of antibiotic-resistant bacteria. JAMA. 1996;275:175
ABSTRACT. Otitis media is the leading indication for
outpatient antimicrobial use in the United States. Over-
diagnosis of and unnecessary prescribing for this condi
tion has contributed to the spread of antimicrobial resis-
tance. A critical step in reducing unnecessary prescribing
is to identify the subset of patients who are unlikely to
benefit from antibiotics. Conscientiously distinguishing
acute otitis media (AOM) from otitis media with effusion
(OME), and deferring antibiotics for OME will accom-
SUPPLEMENT 165
with �-lactam antibiotic resistant nasopharyngeal
flora.22
Children can be protected from resistant bacteria
through the judicious use of antimicrobial agents by
their health care providers. This is the message that
will be most persuasive in discussions between pa
tients and care givers: not that withholding antibiot
ics should be advocated for the benefit of the com
munity as a whole, but that unnecessary antibiotic
use increases the individual patient’s risk that infec
tion will be caused by drug-resistant organisms.
WHY PRINCIPLES FOR JUDICIOUS
13 million prescriptions for pharyngitis.1 In a recent
ANTIMICROBIAL USE NOW?
review of the Medicaid database in Kentucky, 60% of
Practice guidelines have proliferated in recent
years, and US practitioners have been inundated
with more than 1800 sets of guidelines.23 It is impor
tant that the present set of principles are evidence-
based and that they have been developed in an effort
to improve both patient care and the public health, as
opposed to containing costs or restricting care. They
were developed in response to concern from profes
sional organizations, physicians, and public health
officials about the need to promote “judicious anti
biotic use.”5,6,24 The principles that follow represent a
multispecialty collaborative effort among members
of Centers for Disease Control and Prevention,
American Academy of Pediatrics, and American
Academy of Family Physicians to assist local groups
that are developing their own guidelines for appro
priate use of antibiotics.
Efforts have been made to ensure that the follow
ing principles are based on scientific evidence from
peer-reviewed literature. For each of the five condi
tions, searches of Medline were conducted for
English-language articles published from January
1966 through July 1996. Search words were related to
the disease entity and the specific question of interest
(for example, “otitis media/prevention and control”
and “prophylaxis”) and the results supplemented by
reviewing articles from bibliographies of textbooks,
review articles, and symposium publications. Ab
stracts and unpublished work were excluded. Em
phasis was placed on randomized controlled trials of
antimicrobial therapy, studies that included a pla
cebo group, studies with strictly defined diagnostic
criteria or bacteriologic confirmation, and studies
among pediatric patients. In some instances, trials
among adults, studies with small sample sizes, or
descriptive studies were considered; these instances
are noted.
The development of principles alone is unlikely to
evoke substantial change. Widespread adoption into
routine clinical practice will occur only through con
certed and sustained efforts to disseminate and pro
mote these messages at national and local medical
meetings. In addition, endorsement by the major
professional organizations as well as by regional and
local opinion leaders will be necessary. However,
changes in practice are most likely to result if input
from local practitioners is considered.25,26 Therefore,
we anticipate that these principles will serve as a
basis for the local development and promotion of
practice guidelines. Improving antimicrobial use also
164 SUPPLEMENT
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will require effective communication with patients
and parents about when antibiotic therapy is or is not
needed. Most importantly, practitioners must see
these principles as sensible and believe the goal of
controlling antimicrobial resistance worthy of the
efforts required to curtail antibiotic use.
Currently, millions of courses of unnecessary an
tibiotics are given each year. From 1990 to 1992,
almost one in six physician office visits resulted in an
antimicrobial prescription. These included �17 mil
lion prescriptions for nonspecific upper respiratory
infection, 16 million prescriptions for bronchitis, and
patients diagnosed with the common cold were
treated with an antibiotic.27
Physicians report many pressures to prescribe un
necessary antibiotics, but most often cited is the un
realistic expectation for antibiotics on the part of
patients or parents.28 However, most parents do not
acknowledge that they pressure their physician for
antibiotics.28 An important recent finding was that
patient satisfaction with an office visit for respiratory
infections was correlated with the quality of the
patient–physician interaction but not with the pre
scription of an antibiotic.29 A national campaign to
improve parental and patient awareness about anti
microbial resistance and unnecessary antibiotic use is
underway.30 Improved understanding by the general
public as well as the realization by physicians that
patient satisfaction is not dependent on prescribing
an antibiotic should help conscientious physicians in
their efforts to restrict antibiotic overuse.
If unnecessary antibiotic use can be curtailed, there
are indications that the community as well as the
individual patient will benefit. In Japan, a remark
able 62% of group A streptococcal isolates were re
sistant to erythromycin in 1974, when macrolides
accounted for 22% of all antibiotic use. By 1988,
macrolides accounted for only 8% of antibiotic use,
and �2% of group A streptococcal isolates were
resistant to erythromycin.31
Similar observations have now been reported for
resistant pneumococci as well. Reviews of antibiotic
resistance patterns in Spain and Iceland have shown
a correlation between those regions with the lowest
antibiotic use and those with the lowest rates of
penicillin-resistant pneumococci.32,33 A small study of
colonization with pneumococci among day care cen
ter attendees in Omaha, although uncontrolled for
the effects of season and other factors, demonstrated
a striking decrease in the proportion of children with
resistant strains—from 53% to 7%— concomitant
with a decrease in antibiotic use by the attendees.34 In
Iceland, publicity campaigns directed at the problem
of pneumococcal resistance and its relationship to
antibiotic use resulted in a decrease in sales of anti
microbial agents and a concomitant decrease in the
prevalence of resistant pneumococcal isolates.35
Reducing the spread of resistant bacterial patho
gens through judicious antimicrobial use is good for
the individual patient and community and is feasi
ble. The specific principles outlined in the accompa
 Principles of Judicious Use of Antimicrobial Agents for Pediatric Upper

Respiratory Tract Infections

Scott F. Dowell, MD, MPH*; S. Michael Marcy, MD‡; William R. Phillips, MD, MPH§;

Michael A. Gerber, MD�; and Benjamin Schwartz, MD*

ABSTRACT. This article introduces a set of principles
to define judicious antimicrobial use for five conditions
that account for the majority of outpatient antimicrobial
use in the United States. Data from the National Center
for Health Statistics indicate that in recent years, approx
imately three fourths of all outpatient antibiotics have
been prescribed for otitis media, sinusitis, bronchitis,
pharyngitis, or nonspecific upper respiratory tract infec
tion.1 Antimicrobial drug use rates are highest for chil
dren1; therefore, the pediatric age group represents the
focus for the present guidelines. The evidence-based
principles presented here are focused on situations in
which antimicrobial therapy could be curtailed without
compromising patient care. They are not formulated as
comprehensive management strategies. For most upper
respiratory infections that require antimicrobial treat
ment, there are several appropriate oral agents from
which to choose. Although the general principles of se
lecting narrow-spectrum agents with the fewest side ef
fects and lowest cost are important, the principles that
follow include few specific antibiotic selection recom
mendations. Pediatrics 1998;101:163–165; antimicrobial
resistance, antimicrobial use, upper respiratory infection,
otitis media, pediatrics, sinusitis.
THE IMPORTANCE OF JUDICIOUS
taxime.4 In response to this growing problem, control
ANTIMICROBIAL USE AND NEED FOR SPECIFIC
of the spread of antimicrobial resistance has been
PRINCIPLES
resistant Neisseria gonorrhea, Shigella dysenteriae, or
Pseudomonas aeruginosa.
Antimicrobial resistance among respiratory patho
gens has become a common clinical problem and its
management a part of routine office practice. Cur
rently, �90% of Moraxella catarrhalis and 25% of non-
typeable Haemophilus influenzae produce �-lacta
mase,3 requiring treatment with �-lactamase-stable
cephalosporins or combination drugs that include
�-lactamase inhibitors such as amoxicillin-clavu
lanate.
The sense of urgency for the control of resistance
in community-acquired pathogens has come in re
sponse to the recent dramatic emergence of illness
caused by multiply drug-resistant Streptococcus pneu
moniae. In the United States, the pneumococcus was
almost universally sensitive to penicillin until the
1980s. In the last several years, however, there has
been a rapid increase in the number of strains resis
tant to penicillin, extended-spectrum cephalosporins,
and many other antibiotics. In 1994 in Atlanta, �25%
of invasive pneumococcal isolates were nonsuscep
tible to penicillin, and 9% were resistant to cefo

identified as a priority by many organizations, in

T
he emergence of bacterial strains that are in
creasingly resistant to antimicrobial agents is a
growing national and worldwide concern. The
specter of a “post-antimicrobial era,” raised several
years ago,2 has been given credence by the spread of
organisms such as vancomycin-resistant enterococci
and multidrug-resistant tuberculosis, both essen
tially untreatable with routinely available antibiotics.
Such infections remain primarily confined for the
present to populations with special vulnerability,
such as those in hospital intensive care units or high-
risk populations in the inner cities. Practitioners may
more frequently encounter treatment dilemmas
resulting from organisms such as multiply drug-
From the *Childhood and Respiratory Diseases Branch, National Centers
antibiotic use has been identified as a risk factor for
for Infectious Diseases, Centers for Disease Control and Prevention, At
cluding the Centers for Disease Control and Preven
tion, the American Society for Microbiology, the
World Health Organization, the American Academy
of Family Physicians, and the American Academy of
Pediatrics.5–7
The widespread use of antimicrobials, whether ap
propriate or inappropriate, has driven the emergence
and spread of resistant organisms. The association of
resistance with the use of antibiotics has been docu
mented in both inpatient8 and outpatient9 settings.
For example, more than five cross-sectional studies
have documented that the likelihood of culturing a
resistant strain of pneumococcus from the nasophar
ynx is increased if the patient recently completed a
course of antibiotics.9 –14 More importantly, among
patients with invasive pneumococcal disease, recent

lanta, Georgia; ‡Kaiser Permanente, Panorama City, California; §Northwest

infection with multiply drug-resistant strains in

Family Medicine, Seattle, Washington; and �Connecticut Children’s Medical
more than seven studies that have addressed this
Center, Hartford, Connecticut.
question.10,15–21 This process can be reversed through
Received for publication Aug 8, 1997; accepted Sep 11, 1997.
judicious use of antibiotics, as illustrated by the ob
Reprint requests to (S.F.D.) Centers for Disease Control and Prevention,

Mailstop C-23, 1600 Clifton Rd, NE, Atlanta, GA 30333.

servation that terminating �-lactam antibiotic pro

PEDIATRICS (ISSN 0031 4005). Copyright © 1998 by the American Acad
phylaxis and thereby reducing selective pressure
emy of Pediatrics.
leads to a reduction in the proportion of patients

PEDIATRICS Vol. 101 No. 1 January 1998 163

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(P � .9); and 35% reported clinical improvement,
compared with 31% of those treated with placebo
(P � .6).
Thus, mucopurulent rhinitis is part of the natural
course of viral rhinosinusitis, and there is no good
evidence that children with this syndrome benefit
from treatment with antimicrobials unless symptoms
persist for 10 to 14 days without improvement. The
recent emergence of resistant pneumococci, together
with evidence that children on antimicrobials are at
increased risk, suggests that antimicrobials should be
withheld from patients with colds accompanied by
mucopurulent rhinitis.
ACKNOWLEDGMENTS
We thank Drs Leah Raye Mabry and Doug Long and members
of the Committee on Infectious Diseases of the American Acad
emy of Pediatrics for their careful review of this paper.
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