PEDIATRICS Vol. 101 No. 1 Supplement January 1998, pp. 181-184

The Common ColdPrinciples of Judicious Use of Antimicrobial Agents

Nancy Rosenstein^*, William R. Phillips^§, Michael A. Gerber, S. Michael Marcy, Benjamin Schwartz^*, and Scott F. Dowell^*

From the ^* Childhood and Respiratory Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, US Department of Health and Human Services, Atlanta, Georgia;  Kaiser Permanente, Panorama City, California; ^§ Northwest Family Medicine, Seattle, Washington; and  Connecticut Children's Medical Center, Hartford, Connecticut.

	ABSTRACT

Top Abstract References

Most children will suffer between 3 and 8 colds per year, and over half of patients seen for the common cold are given an antimicrobial prescription. Unnecessary 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 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.

	PRINCIPLES

1. Antimicrobial agents should not be given for the common cold.
2. Mucopurulent rhinitis (thick, opaque, or discolored nasal discharge) frequently accompanies the common 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 nonspecific upper respiratory tract infection (URI). The acute illness typically is characterized by rhinorrhea, sore throat, cough, and fever. Because of the difficulty 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 common 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 duration.⁸

Rhinosinusitis and mucopurulent rhinitis are almost 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, tetracycline, or placebo showed similar results: 4.6% of the placebo group either did not improve or presented with evidence of a complication (eg, pneumonia) by 8 days, compared with 4.6% of the antimicrobial 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 doxycycline or placebo, showed a reduction in the proportion with rhinorrhea at day 5 that was no longer apparent by day 10.¹² More recently, a trial of treatment with amoxicillin/clavulanate versus placebo among 314 adults with cold symptoms showed that antimicrobial treatment, although not beneficial overall, was helpful at day 5 in a subgroup of patients with isolation of Streptococcus pneumoniae, Moraxella catarrhalis, or Haemophilus influenzae on a nasal swab.¹³ Given the modest benefit of antimicrobial agents even in these subgroups and the lack of benefit in most other studies (Table)1, antimicrobial agents are not indicated for treatment of viral rhinosinusitis.

The agents causing the common cold identified most commonly are rhinoviruses and coronaviruses, which together account for up to 60% of infections.^2,14,15 Because these viruses are difficult to identify, 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 sequential outbreaks caused by different viruses, such as respiratory syncytial virus; influenza virus; coronavirus; rhinovirus; and parainfluenza 1, 2, and 3 viruses, interspersed with endemic infections caused by others, such as respiratory adenovirus. Occasionally, clinical findings may suggest a specific viral agent; some respiratory adenovirus infections (such as serotypes 3, 4, and 7) may present with pharyngitis 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 common cold also may precede or accompany focal infections 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 begun 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 Furthermore, this approach is less effective than standard 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 reduction in symptoms may be larger than the marginal benefit in symptoms demonstrated in certain subgroups 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 without the risk of antimicrobial-resistant bacterial colonization or infection.
  Mucopurulent rhinitis (thick, opaque, or discolored 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 predictable course. Unnecessary antimicrobial therapy can be avoided by recognizing the signs and symptoms 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 inoculation 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 irritation. Within a few hours, sneezing and watery nasal discharge may occur, often accompanied by systemic complaints such as low-grade fever, malaise, headache, anorexia, and myalgias.²⁶ Cough occurs in 60% to 80% of viral rhinosinusitis^15,27,28 and does not necessarily suggest a bacterial etiology. One to three days after the onset of illness, nasal secretions typically become thicker and more mucopurulent because they contain desquamated epithelial cells, polymorphonuclear cells, and bacteria that normally colonize the upper respiratory tract.²⁸ Physicians often 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 rhinosinusitis with little time for improvement between episodes.

In 1984, Todd³² randomized 142 children with mucopurulent nasopharyngitis into groups that received either antimicrobials (cephalexin), symptomatic therapy, or placebo. Although bacteria often were identified in nasal secretions, antimicrobial treatment did not reduce the number of potentially pathogenic organisms obtained from nasopharyngeal 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 (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.

	FOOTNOTES

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.

	ACKNOWLEDGMENTS

We 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 review of this paper.

	ABBREVIATIONS

URI, upper respiratory tract infection.

	REFERENCES

Top Abstract References

1. Gwaltney JM Acute community acquired sinusitis. Clin Infect Dis. 1996; 23:1209-1225 [Medline]
2. Monto AS, Ullman BM Acute respiratory illness in an American community. The Tecumseh study. JAMA. 1974; 227:164-169 [Abstract/Free Full Text]
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 common 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 [CrossRef][Medline]
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 [Medline]
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 [CrossRef][Medline]
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 respiratory 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 [CrossRef][Medline]
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, Effects of antibiotic treatment in the subset of common-cold patients who have bacteria in nasopharyngeal secretions. Lancet. 1996; 347:1507-1510 [CrossRef][Medline]
14. Anderson LJ, Patriarca PA, Hierholzer JC, Noble GR Viral respiratory illnesses. Med Clin North Am. 1983; 67:1009-1030 [Medline]
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, Treatment of acute streptococcal pharyngitis and prevention of rheumatic fever: a statement for health professionals. Pediatrics. 1995; 96:758-764 [Abstract/Free Full Text]
17. Berman S Otitis media in children. N Engl J Med. 1995; 332:1560-155 [Free Full Text]
18. Wald ER Sinusitis in children. N Engl J Med. 1992; 326:319-323 [Medline]
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 [Medline]
20. Biedel CW Modification of recurrent otitis media by short-term sulfonamide therapy. Am J Dis Child. 1978; 132:681-683 [Abstract/Free Full Text]
21. 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 Otolaryngol. 1994; 114:182-187 [Medline]
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 [CrossRef][Medline]
23. Dowell SF, Marcy SM, Phillips WR, Otitis mediaprinciples of judicious use of antimicrobial agents. Pediatrics. 1998; 101(suppl):165-171 [Abstract/Free Full Text]
24. Berman S, Nuss R, Roark R, Huber-Navin C, Grose K, Herrera M Effectiveness of continuous vs. intermittent amoxicillin to prevent episodes of otitis media. Pediatr Infect Dis J. 1992; 11:63-67 [Medline]
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 [Medline]
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 common cold. Am J Public Heath. 1962; 52:940-945 [CrossRef]
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 evaluation. Pediatr Infect Dis J. 1984; 3:226-232 [Medline]
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 [Abstract/Free Full Text]
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 controlled study of the effect of oral penicillin G in the treatment of non-specific upper respiratory infections. Am J Med. 1954; 16:804-809 [CrossRef][Medline]
34. Hardy LM, Traisman HS Antibiotics and chemotherapeutic agents in the treatment of uncomplicated respiratory infections in children. J Pediatr. 1956; 48:146-156 [CrossRef][Medline]
35. Townsend EH Jr Chemoprophylaxis during respiratory infection in private practice. Am J Dis Child. 1960; 99:566-573 [Abstract/Free Full Text]
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 [Medline]
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