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Pediatric Drugs

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01-03-2008 | Current Opinion

Acute Otitis Media in Children

Association with Day Care Centers — Antibacterial Resistance, Treatment, and Prevention

Authors: Dr David Greenberg, Sigalit Hoffman, Eugene Leibovitz, Ron Dagan

Published in: Pediatric Drugs | Issue 2/2008

Abstract

Children attending day care centers (DCCs) frequently carry antibacterial-resistant organisms in their nasopharynx, leading to acute otitis media (AOM) that may be refractory to antibacterial treatment. The development and spread of resistant organisms are facilitated in DCCs as a result of the following: (i) large numbers of children; (ii) frequent close person-to-person contact; and (iii) a wide use of antimicrobial medications. Intensive antimicrobial usage provides the selection pressure that favors the emergence of resistant organisms, while DCCs provide an ideal environment for transmission of these organisms.

The American Academy of Pediatrics and American Academy of Family Physicians’ guidelines recommend high-dose amoxicillin/clavulanic acid (rather than amoxicillin alone) as the first therapeutic choice in the treatment of AOM in children attending DCCs. The introduction of the 7-valent pneumococcal conjugated vaccine (PCV7) had a major role in decreasing the number of episodes of Streptococccus pneumoniae AOM secondary to the serotypes included in the vaccine. It also had a major role in reducing the nasopharyngeal carriage of vaccine-type S. pneumoniae (and in particular of antibacterial-resistant organisms), preventing, in this way, its spread to contacts in the community. However, the recent observation of increased rates of antibacterial-resistant non-vaccine serotype S. pneumoniae may erode the success of PCV7.

Culpepper L, Froom J, Barteids AI, et al. Acute otitis media in adults: a report from the International Primary Care Network. J Am Board Fam Pract 1993; 6: 333–9PubMed

Faden H, Duffy L, Boeve M. Otitis media: back to basics. Pediatr Infect Dis J 1998; 17: 1105–12; quiz 1112–3PubMedCrossRef

Pelton SI. New concepts in the pathophysiology and management of middle ear disease in childhood. Drugs 1996; 52Suppl. 2: 62–6; discussion 66–7PubMedCrossRef

Teele DW, Klein IO, Rosner B. Epidemiology of otitis media during the first seven years of life in children in greater Boston: a prospective, cohort study. I Infect Dis 1989; 160: 83–94CrossRef

Klein IO, Teele DW, Pelton SI. New concepts in otitis media: results of investigations of the Greater Boston Otitis Media Study Group. Adv Pediatr 1992; 39: 127–56PubMed

Hoberman A, Marchant CD, Kaplan SL, et al. Treatment of acute otitis media consensus recommendations. Clin Pediatr (Phila) 2002; 41: 373–90CrossRef

Dewey C, Midgeley E, Maw R. The relationship between otitis media with effusion and contact with other children in a British cohort studied from 8 months to 3½ years. The ALSPAC (Avon Longitudinal Study of Pregnancy and Childhood) Study Team. Int I Pediatr Otorhinolaryngol 2000; 55: 33–45CrossRef

Ross AK, Croft PR, Collins M. Incidence of acute otitis media in infants in a general practice. I R Coll Gen Pract 1988; 38: 70–2

Giebink GS, Berzins IK, Marker SC, et al. Experimental otitis media after nasal inoculation of Streptococcus pneumoniae and influenza A virus. Infect Immun 1980; 30: 445–50PubMed

10.

McCullers IA, Karlstrom A, Iverson AR, et al. Novel strategy to prevent otitis media caused by colonizing Streptococcus pneumoniae. PLoS Pathogens 2007; 3: 1–3CrossRef

11.

Henderson FW, Collier AM, Sanyal MA, et al. A longitudinal study of respiratory viruses and bacteria in the etiology of acute otitis media with effusion. N Engl I Med 1982; 306: 1377–83CrossRef

12.

Glezen WP, Taber LH, Frank AL, et al. Influenza virus infections in infants. Pediatr Infect Dis I 1997; 16: 1065–8CrossRef

13.

Glezen WP. Prevention of acute otitis media by prophylaxis and treatment of influenza virus infections. Vaccine 2001; 19: S56–8CrossRef

14.

Dagan R, Barkay G, Leibovitz E, et al. Will reduction of antibiotic use reduce antibiotic resistance? The pneumococcus paradigm. Pediatr Infect Dis I 2006; 25: 981–6CrossRef

15.

Giebink GS. The microbiology of otitis media. Pediatr Infect Dis J 1989; 8: S18–20PubMedCrossRef

16.

Bluestone CD, Stephenson IS, Martin LM. Ten-year review of otitis media pathogens. Pediatr Infect Dis I 1992; 11: S7–11CrossRef

17.

Block SL. Causative pathogens, antibiotic resistance and therapeutic considerations in acute otitis media. Pediatr Infect Dis I 1997; 16: 449–56CrossRef

18.

Jacobs MR, Dagan R, Appelbaum PC, et al. Prevalence of antimicrobial-resistant pathogens in middle ear fluid: multinational study of 917 children with acute otitis media. Antimicrob Agents Chemother 1998; 42: 589–95PubMed

19.

Gungor A, Bluestone CD. Antibiotic theory in otitis media. Curr Allergy Asthma Rep 2001; 1: 364–72PubMedCrossRef

20.

Sagraves R. Increasing antibiotic resistance: its effect on the therapy for otitis media. I Pediatr Health Care 2002; 16: 79–85

21.

Faden H, Duffy L, Wasielewski R, et al. Relationship between nasopharyngeal colonization and the development of otitis media in children. I Infect Dis 1997; 175: 1440–5CrossRef

22.

Harabuchi Y, Faden H, Yamanaka N, et al. Nasopharyngeal colonization with nontypeable Haemophilus influenzae and recurrent otitis media. I Infect Dis 1994; 170: 862–6CrossRef

23.

Leach AI, Boswell IB, Asche V, et al. Bacterial colonization of the nasopharynx predicts very early onset and persistence of otitis media in Australian aboriginal infants. Pediatr Infect Dis I 1994; 13: 983–9CrossRef

24.

American Academy of Pediatrics and American Academy of Family Physicians. Subcommittee on Management of Acute Otitis Media. Clinical practice guideline: diagnosis and management of acute otitis media. Pediatrics 2004; 113: 1451–65CrossRef

25.

Niemela M, Uhari M, Jounio-Ervasti K, et al. Lack of specific symptomatology in children with acute otitis media. Pediatr Infect Dis J 1994; 13: 765–8PubMedCrossRef

26.

Bluestone CD. Pathogenesis of otitis media: role of eustachian tube. Pediatr Infect Dis J 1996; 15: 281–91PubMedCrossRef

27.

Heikkinen T, Thint M, Chonmaitree T. Prevalence of various respiratory viruses in the middle ear during acute otitis media. N Engl J Med 1999; 340: 260–4PubMedCrossRef

28.

Thorburn CE, Knott SJ, Edwards DI. In vitro activities of oral beta-lactams at concentrations achieved in humans against penicillin-susceptible and -resistant pneumococci and potential to select resistance. Antimicrob Agents Chemother 1998; 42: 1973–9PubMed

29.

Doern GV, Pfaller MA, Kugler K, et al. Prevalence of antimicrobial resistance among respiratory tract isolates of Streptococcus pneumoniae in North America: 1997 results from the SENTRY antimicrobial surveillance program. Clin Infect Dis 1998; 27: 764–70PubMedCrossRef

30.

Dagan R. Clinical significance of resistant organisms in otitis media. Pediatr Infect Dis J 2000; 19: 378–82PubMedCrossRef

31.

Leibovitz E, Raiz S, Piglansky L, et al. Resistance pattern of middle ear fluid isolates in acute otitis media recently treated with antibiotics. Pediatr Infect Dis J 1998; 17: 463–9PubMedCrossRef

32.

Leibovitz E, Dagan R. Antibiotic treatment for acute otitis media. Int J Antimicrob Agents 2000; 15: 169–77PubMedCrossRef

33.

Leibovitz E, Dagan R. Otitis media therapy and drug resistance. Part I: management principles. Infect Med 2001: 212–6

34.

Leibovitz E, Dagan R. Otitis media therapy and drug resistance. Part 2: current concepts and new directions. Infect Med 2001: 263–70

35.

Sinus and Allergy Health Partnership. Antibacterial treatment guidelines for acute bacterial rhinosinusitis. Otolaryngol Head Neck Surg 2000; 123: S5–31CrossRef

36.

Doern GV, Brueggemann AB, Pierce G, et al. Antibiotic resistance among clinical isolates of Haemophilus influenzae in the United States in 1994 and 1995 and detection of beta-lactamase-positive strains resistant to amoxicillin-clavulanate: results of a national multicenter surveillance study. Antimicrob Agents Chemother 1997; 41: 292–7PubMed

37.

Jacobs MR, Felmingham D, Appelbaum PC, et al. The Alexander Project 1998–2000: susceptibility of pathogens isolated from community-acquired respiratory tract infection to commonly used antimicrobial agents. J Antimicrob Chemother 2003; 52: 229–46PubMedCrossRef

38.

Dagan R, Givon-Lavi N, Shkolnik L, et al. Acute otitis media caused by antibiotic-resistant Streptococcus pneumoniae in Southern Israel: implicaiton for immunizing with conjugate vaccines. J Inf Dis 2000; 181: 1322–9CrossRef

39.

Hausdorff WP, Yothers G, Dagan R, et al. Multinational study of pneumococcal serotypes causing acute otitis media in children. Pediatr Infect Dis J 2002; 21: 1008–16PubMedCrossRef

40.

Del Beccaro MA, Mendelman PM, Inglis AF, et al. Bacteriology of acute otitis media: a new perspective. J Pediatr 1992; 120: 81–4PubMedCrossRef

41.

Pichichero ME, Pichichero CL. Persistent acute otitis media: I. Causative pathogens. Pediatr Infect Dis J 1995; 14: 178–83PubMedCrossRef

42.

del Castillo F, Garcia-Perea A, Baquero-Artigao F. Bacteriology of acute otitis media in Spain: a prospective study based on tympanocentesis. Pediatr Infect Dis J 1996; 15: 541–3PubMed

43.

Jorgensen JH. Update on mechanisms and prevalence of antimicrobial resistance in Haemophilus influenzae. Clin Infect Dis 1992; 14: 1119–23PubMedCrossRef

44.

Mendelman PM, Chaffin DO, Stull TL, et al. Characterization of non-β-lactamase-mediated ampicillin resistance in Haemophilus influenzae. Antimicrob Agents Chemother 1984; 25: 747–53CrossRef

45.

Hasegawa Y, Yamamoto K, Chiba N, et al. Diversity of ampicillin-resistance genes in Haemophilus influenzae in Japan and the United States. Microb Drug Resist 2003; 9: 39–46PubMedCrossRef

46.

Kaczmarek FS, Gootz TD, Dib-Hajj F, et al. Genetic and molecular characterization of β-lactamase-negative ampicillin-resistant Haemophilus influenzae with unusually high resistance to ampicillin. Antimicrob Agents Chemother 2004; 48: 1630–9PubMedCrossRef

47.

Klein JO. Microbiologic efficacy of antibacterial drugs for acute otitis media. Pediatr Infect Dis J 1993; 12: 973–5PubMedCrossRef

48.

Howie VM, Ploussard JH. Efficacy of fixed combination antibiotics versus separate components in otitis media: effectiveness of erythromycin estrolate, triple sulfonamide, ampicillin, erythromycin estolate- triple sulfonamide, and placebo in 280 patients with acute otitis media under two and one-half years of age. Clin Pediatr (Phila) 1972; 11: 205–14CrossRef

49.

Howie VM, Dillard R, Lawrence B. In vivo sensitivity test in otitis media: efficacy of antibiotics. Pediatrics 1985; 75: 8–13PubMed

50.

Eskola J, Kilpi T, Palmu A, et al. Efficay of a pneumococcal conjugate vaccine against acute otitis media. N Engl J Med 2001; 344: 403–9PubMedCrossRef

51.

Kilpi T, Ahman H, Jokinen J, et al. Protective efficacy of a second pneumococcal conjugate vaccine against pneumococcal acute otitis media in infants and children: randomized, controlled trial of a 7-valent pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine in 1666 children. Clin Infect Dis 2003; 37: 1155–64PubMedCrossRef

52.

Casey J, Pichichero ME. Changes in frequency and pathogens causing acute otitis media in 1995–2003. Pediatr Infect Dis J 2004; 23: 824–8PubMedCrossRef

53.

Block SL, Hedrick J, Harrison CJ, et al. Community-wide vaccination with the heptavalent pneumococcal conjugate alters the microbiology of acute otitis media. Pediatr Infect Dis J 2004; 23: 829–33PubMedCrossRef

54.

Reichler MR, Allphin AA, Breiman RF, et al. The spread of multiply resistant Streptococcus pneumoniae in a day care center in Ohio. J Infect Dis 1992; 166: 1346–53PubMedCrossRef

55.

Cherian T, Steinhoff M, Harrison LH, et al. A cluster of invasive pneumococcal disease in young children in child care. JAMA 1994; 271: 695–7PubMedCrossRef

56.

Barnes DM, Whittier S, Gilligan PH, et al. Transmission of multiply-resistant serotype 23F Streptococcus pneumoniae in group day care: evidence suggesting capsular transformation of the resistant strain in vivo. J Infect Dis 1995; 171: 890–6PubMedCrossRef

57.

Yagupsky P, Porat N, Fraser D, et al. Acquisition, carriage, and transmission of pneumococci with decreased antibiotic susceptibility in young children attending a day care facility in southern Israel. J Infect Dis 1998; 177: 1003–12PubMedCrossRef

58.

Givon-Lavi N, Dagan R, Fraser D, et al. Marked differences in pneumococcal carriage and resistance patterns between day care centers located within a small area. Clin Infect Dis 1999; 29: 1274–80PubMedCrossRef

59.

Huang SS, Finkelstein JA, Lipsitch M. Modeling community and individual-level effects of child-care attendance on pneumococcal carriage. Clin Infect Dis 2005; 40: 1215–22PubMedCrossRef

60.

Rosenfeld RM, Vertrees JE, Carr J, et al. Clinical efficacy of antimicrobial drugs for acute otitis media: meta-analysis of 5400 children from thirty-three randomized trials. J Pediatr 1994; 124: 355–67PubMedCrossRef

61.

Del Mar C, Glasziou P, Hayem M. Are antibiotics indicated as initial treatment for children with acute otitis media? A meta-analysis. BMJ 1997; 314: 1526–9PubMedCrossRef

62.

Glasziou PP, Del Mar CB, Hayem M, et al. Antibiotics for acute otitis media in children. Cochrane Database Syst Rev 2000; (4): CD000219

63.

Appleman C, van Baien F, Van de Lisdonk E, et al. Otitis media acuta. NHG-standard (eerste heirziening). Huisarts Wet 1999; 42: 362–6

64.

Otters HBM, van der Wouden JC, Schellevis FG, et al. Trends in prescribing antibiotics for children in Dutch general practice. J Antimicrob Chemother 2004; 53: 361–6PubMedCrossRef

65.

van Buchem FL, Peeters MF, van’t Hof MA. Acute otitis media: a new treatment strategy. BMJ (Clin Res Ed) 1985; 290: 1033–7CrossRef

66.

Little P, Gould C, Moore M, et al. Predictors of poor outcome and benefits from antibiotics in children with acute otitis media: pragmatic randomised trial. BMJ 2002; 325: 22PubMedCrossRef

67.

Dagan R, McCracken Jr GH. Flaws in design and conduct of clinical trials in acute otitis media. Pediatr Infect Dis J 2002; 21: 894–902PubMedCrossRef

68.

Wald E. Acute otitis media: more trouble with the evidence. Pediatr Infect Dis J 2003; 22: 103–4PubMed

69.

Rovers MM, Glasziou P, Appelman CL, et al. Antibiotics for acute otitis media: a meta-analysis with individual patient data. Lancet 2006; 368: 1429–35PubMedCrossRef

70.

Kaleida PH, Casselbrant ML, Rockette HE, et al. Amoxicillin or myringotomy or both for acute otitis media: results of a randomized clinical trial. Pediatrics 1991; 87: 466–74PubMed

71.

Van Zuijlen DA, Schilder AG, Van Balen FA, et al. National differences in incidence of acute mastoiditis: relationship to prescribing patterns of antibiotics for acute otitis media? Pediatr Infect Dis J 2001; 20: 140–4PubMedCrossRef

72.

Piglansky L, Leibovitz E, Raiz S, et al. Bacteriologic and clinical efficacy of high dose amoxicillin for therapy of acute otitis media in children. Pediatr Infect Dis J 2003; 22: 405–13PubMed

73.

Dagan R, Hoberman A, Johnson C, et al. Bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate in children with acute otitis media. Pediatr Infect Dis J 2001; 20: 829–37PubMedCrossRef

74.

Green SM, Rothrock SG. Single-dose intramuscular ceftriaxone for acute otitis media in children. Pediatrics 1993; 91: 23–30PubMed

75.

Leibovitz E, Piglansky L, Raiz S, et al. Bacteriologic and clinical efficacy of one day vs three day intramuscular ceftriaxone for treatment of nonresponsive acute otitis media in children. Pediatr Infect Dis J 2000; 19: 1040–5PubMedCrossRef

76.

Dowell SF, Butler JC, Giebink GS, et al. Acute otitis media: management and surveillance in an era of pneumococcal resistance: a report from the Drug-resistant Streptococcus pneumoniae Therapeutic Working Group. Pediatr Infect Dis J 1999; 18: 1–9PubMed

77.

Rosenfeld RM, Kay D. Natural history of untreated otitis media. In: Rosenfeld RM, Bluestone CD, editors. Evidence-based otitis media. 2nd ed. Hamilton (ON): BC Becker, Inc., 2003: 180–98

78.

Uhari M, Kontiokari T, Koskela M, et al. Xylitol chewing gum in prevention of acute otitis media: double blind randomised trial. BMJ 1996; 313: 1180–84PubMedCrossRef

79.

Uhari M, Tapiainen T, Kontiokari T. Xylitol in preventing acute otitis media. Vaccine 2000; 19: S1144–7CrossRef

80.

Hautalahti O, Renko M, Tapiainen T, et al. Failure of xylitol given three times a day for preventing acute otitis media. Pediatr Infect Dis J 2007; 26: 423–7PubMedCrossRef

81.

Black S, Shinefield H, Fireman B, et al. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Pediatr Infect Dis J 2000; 19: 187–95PubMedCrossRef

82.

Fireman B, Black SB, Shinefield HS, et al. Impact of the pneumococcal conjugate vaccine on otitis media. Pediatr Infect Dis J 2003; 22: 10–6PubMedCrossRef

83.

Whitney CG, Pilishvili T, Farley MM, et al. Effectiveness of seven-valent pneumococcal conjugate vaccine against pneumococcal disease: a matched case-control study. Lancet 2006; 368: 1495–502PubMedCrossRef

84.

Grijalva CG, Nuorti JP, Arbogast PG, et al. Decline in pneumonia admissions after routine childhood immunisation with pneumococcal conjugate vaccine in the USA: a time-series analysis. Lancet 2007; 369: 1179–86PubMedCrossRef

85.

Poehling KA, Szilagyi PG, Grijalva CG, et al. Reduction of frequent otitis media and pressure-equilizing tube insertions in children after introduction of pneumococcal conjugate vaccine. Pediatrics 2007; 119: 707–15PubMedCrossRef

86.

Dagan R, Melamed R, Muallem M, et al. Reduction of nasopharyngeal carriage during the second year of life by a heptavalent conjugate pneumococcal vaccine. J Infect Dis 1996; 174: 1271–8PubMedCrossRef

87.

Dagan R, Givon-Lavi N, Zamir O, et al. Reduction of nasopharyngeal carriage of Streptococccus pneumoniae after administration of a 9-valent pneumococcal conjugate vaccine in toddlers attending day care centers. J Infect Dis 2002; 185: 927–36PubMedCrossRef

88.

Dagan R, Givon-Lavi N, Zamir O, et al. Effect of a nonavalent conjugate vaccine on carriage of antibiotic-resistant Streptococcus pneumoniae in day care centers. Pediatr Infect Dis J 2003; 22: 532–9PubMed

89.

O’Brien KL, Dagan R. The potential indirect effect of conjugate pneumococcal vaccines. Vaccine 2003; 21: 1815–25PubMedCrossRef

90.

Bogaert D, De Groot R, Hermans PW. Streptococcus pneumoniae colonization: the key to pneumococcal disease. Lancet Infect Dis 2004; 4: 144–54PubMedCrossRef

91.

Dagan R, Givon-Lavi N, Shkolnik L, et al. Acute otitis media caused by antibiotic-resistant Streptococcus pneumoniae in southern Israel: implication for immunizing with conjugate vaccines. J Infect Dis 2000; 181: 1322–9PubMedCrossRef

92.

Givon-Lavi N, Fraser D, Dagan R. Vaccination of day-care center atendees reduces carriage of Streptococcus pneumoniae among their younger siblings. Pediatr Infect Dis J 2003; 22: 524–32PubMed

93.

Madhi SA, Klugman KP, and The Vaccine Trialist Group. A role for Streptococcus pneumoniae in virus-associated pneumonia. Nat Med 2004; 10: 811–3PubMedCrossRef

94.

Dagan R, Sikuler-Cohen M, Zamir O, et al. Effect of a conjugate pneumococcal vaccine on the occurrence of respiratory infections and antibiotic use in day-care center attendees. Pediatr Infect Dis J 2001; 20: 951–8PubMedCrossRef

95.

Porat N, Barkai G, Jacobs MR, et al. Four antibiotic-resistant Streptococcus pneumoniae clones unrelated to the pneumococcal conjugate vaccine serotypes, including 2 new serotypes, causing acute otitis media in southern Israel. J Infect Dis 2004; 189: 385–92PubMedCrossRef

96.

Porat N, Arguedas A, Spratt BG, et al. Emergence of penicillin-nonsusceptible Streptococcus pneumoniae clones expressing serotypes not present in the antipneumococcal conjugate vaccine. J Infect Dis 2004; 190: 2154–61PubMedCrossRef

97.

Principi N, Esposito S. Are we ready for universal influenza vaccination in paediatrics? Lancet Infect Dis 2004; 4: 75–83PubMedCrossRef

98.

Clements DA, Langdon L, Bland C, et al. Influenza A vaccine decreases the incidence of otitis media in 6- to 30-month-old children in day care. Arch Pediatr Adolesc Med 1995; 149: 1113–7PubMedCrossRef

99.

Hoberman A, Greenberg DP, Paradise JL, et al. Efficacy of inactivated influenza vaccine in preventing acute otitis media in young children: a randomized controlled trial. JAMA 2003; 290: 1608–16PubMedCrossRef

100.

Vesikari T, Fleming DM, Aristegui JF, et al. Safety, efficacy, and effectiveness of cold-adapted influenza vaccine-trivalent against community-acquired, culture-confirmed influenza in young children attending day care. Pediatrics 2006; 118: 2298–312PubMedCrossRef

101.

Nuorti JP, Butler JC, Farley MM, et al. Cigarette smoking and invasive pneumococcal disease. Active Bacterial Core Surveillance Team. N Engl J Med 2000; 342: 681–9PubMedCrossRef

102.

Greenberg D, Givon-Lavi N, Broides A, et al. The contribution of smoking and exposure to tobacco smoke to Streptococcus pneumoniae and Haemophilus influenzae carriage in children and their mothers. Clin Infect Dis 2006; 42: 897–903PubMedCrossRef

Title: Acute Otitis Media in Children
Association with Day Care Centers — Antibacterial Resistance, Treatment, and Prevention
Authors: Dr David Greenberg
Sigalit Hoffman
Eugene Leibovitz
Ron Dagan
Publication date: 01-03-2008
Publisher: Springer International Publishing
Published in: Pediatric Drugs / Issue 2/2008
Print ISSN: 1174-5878
Electronic ISSN: 1179-2019
DOI: https://doi.org/10.2165/00148581-200810020-00002

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Acute Otitis Media in Children

Association with Day Care Centers — Antibacterial Resistance, Treatment, and Prevention

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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