Principles of Judicious Use of Antimicrobial Agents for Pediatric UpperRespiratory Tract Infections

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

Pediatrics 1998;101;163-165 DOI: 10.1542/peds.101.1.S1.163

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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

Hardy et al34 (1956) 217 Abx* or placebo symptomatic 20%

Rate of all infectious No difference between abx complications abx 15%, and placebo

Townsend35 (1960) 845 Abx† or symptomatic placebo 15%

Rate of all infectious No difference between abx treatment complications abx 14%, and symptomatic

Townsend10 (1962) 781 Abx† or symptomatic symptomatic 9%

Rate of complications (eg., No difference between abx treatment AOM) abx 3.5%, and symptomatic

Lexomboon et al11 (1971) 261 PCN V or tetracycline or symptomatic 2.6%

Not improved or complicated No difference between abx

Gordon et al36 (1974) 89 placebo

Abx‡ or placebo abx 5%, placebo 5%

Improved symptoms or signs and placebo

Abx do not change short-data not provided in term course of URI

Stott and West12 (1976) 212 Doxycycline or placebo publication

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

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

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 Bacterialand Mycotic Diseases, National Center for Infectious Diseases, Centers forDisease Control and Prevention, Public Health Service, US Department ofHealth and Human Services, Atlanta, Georgia; ‡Kaiser Permanente, Pan-orama City, California; §Northwest Family 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.

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

nasal discharge) frequently accompanies the com-mon cold. It is not an indication for antimicrobial treatment unless it persists for �10 to 14 days.

BACKGROUND AND JUSTIFICATION

Recent evidence suggests that the common cold usually includes sinus disease.1 Therefore, viral rhinosinusitis is used in this paper as a

synonym for the common cold syndrome or nonspe-

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

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

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 Bacterialand Mycotic Diseases, National Center for Infectious Diseases, Centers forDisease Control and Prevention, Public Health Service, US Department ofHealth and Human Services, Atlanta, Georgia; ‡Kaiser Permanente, Pan-orama City, California; §Northwest Family 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.

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

nasal discharge) frequently accompanies the com-mon cold. It is not an indication for antimicrobial treatment unless it persists for �10 to 14 days.

BACKGROUND AND JUSTIFICATION

Recent evidence suggests that the common cold usually includes sinus disease.1 Therefore, viral rhinosinusitis is used in this paper as a

synonym for the common cold syndrome or nonspe-

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

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-

180 SUPPLEMENT

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 ofAntimicrobial 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

Bronchitis 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, NationalCenter for Infectious Diseases, Centers for Disease Control and Prevention,Atlanta, Georgia; ‡Kaiser Permanente, Panorama City, California; §North-west Family Medicine, Seattle, Washington; and �Connecticut Children’sMedical 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 Adcad-emy of Pediartics.

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.

EVIDENCE SUPPORTING PRINCIPLES

Regardless of Duration, Nonspecific Cough Illness/Bronchitis in Children Rarely Warrants Antimicrobial Treatment

Seven randomized, placebo-controlled antibiotic tri-als for bronchitis among adult patients have been pub-

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

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

176 SUPPLEMENT

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

Each 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-

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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

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

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, NationalCenter for Infectious Diseases, Centers for Disease Control and Prevention,Atlanta, Georgia; ‡Kaiser Permanente, Panorama City, California; §North-west Family Medicine, Seattle, Washington; and �Connecticut Children’sMedical 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.

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.

ABBREVIATIONS. URI, upper respiratory tract illness; CT, com-puted tomography.

PRINCIPLES 1. Clinical diagnosis of bacterial sinusitis requires

the following: prolonged nonspecific upper respi-ratory signs and symptoms (ie, rhinosinusitis and

174 SUPPLEMENT

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

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

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, NationalCenter for Infectious Diseases, Centers for Disease Control and Prevention,Atlanta, Georgia; ‡Kaiser Permanente, Panorama City, California; §North-west Family Medicine, Seattle, Washington; and �Connecticut Children’sMedical 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.

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.

ABBREVIATIONS. URI, upper respiratory tract illness; CT, com-puted tomography.

PRINCIPLES 1. Clinical diagnosis of bacterial sinusitis requires

the following: prolonged nonspecific upper respi-ratory signs and symptoms (ie, rhinosinusitis and

174 SUPPLEMENT

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,

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

172 SUPPLEMENT

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

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

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 Centersfor Infectious Diseases, Centers for Disease Control and Prevention,Atlanta, Georgia; ‡Kaiser Permanente, Panorama City, California; §North-west Family Medicine, Seattle, Washington; and �Connecticut Children;sMedical Center, Hartford, Connecticut.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.

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

Sore 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 within 9 days of onset is effective in preventing acute rheumatic fever.2 In addition, treatment of group A streptococcal infection may prevent suppurative complications, lead to more rapid resolution of ill-ness, and prevent the spread of infection. Neverthe-less, because most episodes of sore throat are caused

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

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

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 Centersfor Infectious Diseases, Centers for Disease Control and Prevention,Atlanta, Georgia; ‡Kaiser Permanente, Panorama City, California; §North-west Family Medicine, Seattle, Washington; and �Connecticut Children;sMedical Center, Hartford, Connecticut.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.

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

Sore 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 within 9 days of onset is effective in preventing acute rheumatic fever.2 In addition, treatment of group A streptococcal infection may prevent suppurative complications, lead to more rapid resolution of ill-ness, and prevent the spread of infection. Neverthe-less, because most episodes of sore throat are caused

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

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

170 SUPPLEMENT

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.

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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

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.

168 SUPPLEMENT

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

Otitis 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-

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

166 SUPPLEMENT

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

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

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 forInfectious Diseases, Centers for Disease Control and Prevention, Atlanta,Georgia; ‡Kaiser Permanente, Panorama City, California; §Northwest Fam-ily Medicine, Seattle, Washington; and �Connecticut Children’s MedicalCenter, 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.

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

Principles of Judicious Use of Antimicrobial Agents for Pediatric UpperRespiratory Tract Infections

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

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

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- diagnosis of and unnecessary prescribing for this condi-ily Medicine, Seattle, Washington; and �Connecticut Children’s Medical tion has contributed to the spread of antimicrobial resis-Center, Hartford, Connecticut. Received for publication Aug 8, 1997; accepted Sep 11, 1997. tance. A critical step in reducing unnecessary prescribing 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. (OME), and deferring antibiotics for OME will accom-

SUPPLEMENT 165Downloaded from www.pediatrics.org by on July 12, 2005

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 JUDICIOUSANTIMICROBIAL USE NOW?

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

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 13 million prescriptions for pharyngitis.1 In a recent review of the Medicaid database in Kentucky, 60% of 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-

164 SUPPLEMENT Downloaded from www.pediatrics.org by on July 12, 2005

Principles of Judicious Use of Antimicrobial Agents for Pediatric UpperRespiratory 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 JUDICIOUSANTIMICROBIAL USE AND NEED FOR SPECIFIC

PRINCIPLES

The 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 Centersfor Infectious Diseases, Centers for Disease Control and Prevention, At-lanta, Georgia; ‡Kaiser Permanente, Panorama City, California; §NorthwestFamily Medicine, Seattle, Washington; and �Connecticut Children’s MedicalCenter, 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.

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-taxime.4 In response to this growing problem, control of the spread of antimicrobial resistance has been identified as a priority by many organizations, in-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 antibiotic use has been identified as a risk factor for infection with multiply drug-resistant strains in more than seven studies that have addressed this question.10,15–21 This process can be reversed through judicious use of antibiotics, as illustrated by the ob-servation that terminating �-lactam antibiotic pro-phylaxis and thereby reducing selective pressure leads to a reduction in the proportion of patients

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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.

REFERENCES 1. Gwaltney JM. Acute community acquired sinusitis. Clin Infect Dis.

1996;23:1209–1225 2. Monto AS, Ullman BM. Acute respiratory illness in an American com-

munity. The Tecumseh study. JAMA. 1974;227:164–169 3. Badger GF, Dingle JH, Feller AE, Hodges RG, Jordan WS, Rammelkamp

CH Jr. A study of illness in a group of Cleveland families. II. Incidence of the common respiratory diseases. Am J Hyg. 1953;58:31–40

4. Dingle JH, Badger GF, Jordan WS Jr. Common respiratory diseases. In: Illness in the Home: A study of 25 000 Illnesses in a Group of Cleveland Families. Cleveland, OH: The Press of Western Reserve University; 1964:66–88

5. Turner RB. The epidemiology, pathogenesis, and treatment of the com-mon cold. Sem Pediatr Infect Dis. 1995;6:57–61

6. Wald ER, Dashefsky B, Byers C, Guerra N, Taylor F. Frequency and severity of infections in day care. J Pediatr. 1988;112:540–546

7. Mainous AG, Hueston WJ, Clark JR. Antibiotics and upper respiratory infection: do some folks think there is a cure for the common cold? J Fam Pract. 1996;42:357–361

8. Schwartz RH, Freij BJ, ZIAI M, Sheridan MJ. Antimicrobial prescribing for acute purulent rhinitis in children: a survey of pediatricians and family practitioners. Pediatr Infect Dis J. 1997;16:185–190

9. Dowell SF, Schwartz B. Resistant pneumococci: protecting patients through judicious antibiotic use. Am Fam Physician. 1997;15:1647–1654

10. Townsend EJ Jr, Radebaugh JF. Prevention of complications of respira-tory illnesses in a pediatric practice. Semin Pediatr Infect Dis. 1962;266: 683–689

11. Lexomboon U, Duangmani C, Kusalasai V, Sunakorn P, Olson LC, Noyes HE. Evaluation of orally administered antibiotics for treatment of upper respiratory infections in Thai children. J Pediatr. 1971;78:772–778

12. Stott NC, West RR. Randomised controlled trial of antibiotics in patients with cough and purulent sputum. Br Med J. 1976;2:556–559

13. Kaiser L, Lew D, Stalder H, et al. Effects of antibiotic treatment in the subset of common-cold patients who have bacteria in nasopharyngeal secretions. Lancet. 1996;347:1507–1510

14. Anderson LJ, Patriarca PA, Hierholzer JC, Noble GR. Viral respiratory illnesses. Med Clin North Am. 1983;67:1009–1030

15. Horn ME, Brain E, Gregg I, Yealland SJ, Inglis JM. Respiratory viral

infection in childhood. A survey in general practice, Rohampton, 1967–1972. J Hyg. 1975;74:157–168

16. Dajani A, Taubert K, Ferrieri P, et al. Treatment of acute streptococcal pharyngitis and prevention of rheumatic fever: a statement for health professionals. Pediatrics. 1995;96:758–764

17. Berman S. Otitis media in children. N Engl J Med. 1995;332:1560–155 18. Wald ER. Sinusitis in children. N Engl J Med. 1992;326:319–323 19. 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

20. Biedel CW. Modification of recurrent otitis media by short-term sulfon-amide therapy. Am J Dis Child. 1978;132:681–683

21. Prellner K, Fogle-Hansson M, Jorgensen F, Kalm O, Kamme C. Preven-tion of recurrent acute otitis media in otitis-prone children by intermit-tent prophylaxis with penicillin. Acta Otolaryngol. 1994;114:182–187

22. 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

23. Dowell SF, Marcy SM, Phillips WR, et al. Otitis media—principles of judicious use of antimicrobial agents. Pediatrics. 1998;101(suppl): 165–171

24. 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

25. Gwaltney JM, Park J, Paul RA, Edelman DA, O’Connor RR, Turner RB. Randomized controlled trial of clemastine fumarate for treatment of experimental rhinovirus colds. Clin Infect Dis. 1996;22:656–662

26. Cherry JD. The common cold. In: Feigin RD, Cherry JD, eds. Textbook of Pediatric Infectious Diseases. 3rd ed. Philadelphia, PA: WB Saunders; 1992:137–142

27. Jackson GG, Dowling HF, Muldoon RL. Present concepts of the com-mon cold. Am J Public Heath. 1962;52:940–945

28. van Volkenburgh VA, Frost WH. Acute minor respiratory diseases prevailing in a group of families residing in Baltimore, Maryland, 1928–1930. Prevalence, distribution and clinical description of observed cases. Am J Hyg. 1933;17:122–153

29. Todd JK, Todd N, Damato J, Todd WA. Bacteriology and treatment of purulent nasopharyngitis: a double blind, placebo-controlled evalua-tion. Pediatr Infect Dis J. 1984;3:226–232

30. Wald ER, Milmoe GJ, Bowen AD, Ledesma-Medina J, Salamon N, Bluestone CD. Acute maxillary sinusitis in children. N Engl J Med. 1981;13:749–754

31. Cloutier MM. The coughing child. Etiology and treatment of a common symptom. Postgrad Med. 1983;73:169–175

32. Todd JK. Bacteriology and clinical relevance of nasopharyngeal and oropharyngeal cultures. Pediatr Infect Dis J. 1984;3:159–163

33. Cronk GA, Naumann DE, McDermott K, Menter P, Swift MB. A con-trolled study of the effect of oral penicillin G in the treatment of non-specific upper respiratory infections. Am J Med. 1954;16:804–809

34. Hardy LM, Traisman HS. Antibiotics and chemotherapeutic agents in the treatment of uncomplicated respiratory infections in children. J Pe-diatr. 1956;48:146–156

35. Townsend EH Jr. Chemoprophylaxis during respiratory infection in private practice. Am J Dis Child. 1960;99:566–573

36. Gordon M, Lovell S, Dugdale AE. The value of antibiotics in minor respiratory illness in children. A controlled trial. Med J Aust. 1974;1: 304–306

37. 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

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