Current management of pediatric acute otitis media

Expert Review of Anti-Infective Therapy

Volumn 8, Issue 2, 2010, Pages 151-161

  Leibovitz, Eugene ^a   Broides, Arnon ^b   Greenberg, David ^b   Newman, Nitza ^b  

^a BEN GURION UNIVERSITY OF THE NEGEV   (Israel)

^b BEN GURION UNIVERSITY OF THE NEGEV   (Israel)

Author keywords

acute otitis media; antibiotics; guidelines; observation; Streptococcus pneumoniae; vaccines

Indexed keywords

AMOXICILLIN; AMOXICILLIN PLUS CLAVULANIC ACID; AZITHROMYCIN; CEFTRIAXONE; CLINDAMYCIN; PNEUMOCOCCUS VACCINE; ANTIINFECTIVE AGENT;

ACTIVE IMMUNIZATION; ACUTE OTITIS MEDIA; ANTIBIOTIC THERAPY; CLINICAL OBSERVATION; DISEASE SEVERITY; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG HYPERSENSITIVITY; DRUG MEGADOSE; ERADICATION THERAPY; HAEMOPHILUS INFLUENZAE; HUMAN; INFECTION PREVENTION; INFECTION RESISTANCE; MORAXELLA CATARRHALIS; NONHUMAN; PATIENT ASSESSMENT; RECURRENT INFECTION; REVIEW; SEROTYPE; STREPTOCOCCUS GROUP A; STREPTOCOCCUS PNEUMONIAE; TREATMENT OUTCOME; ACUTE DISEASE; ANTIBIOTIC RESISTANCE; INFANT; MICROBIOLOGY; OTITIS MEDIA; PRESCHOOL CHILD;

ACUTE DISEASE; ANTI-BACTERIAL AGENTS; CHILD, PRESCHOOL; DRUG RESISTANCE, BACTERIAL; HUMANS; INFANT; OTITIS MEDIA; PNEUMOCOCCAL VACCINES;

EID: 85047688152     PISSN: 14787210     EISSN: 17448336     Source Type: Journal    
DOI: 10.1586/eri.09.112     Document Type: Review

References (112)

1. Culpepper L, Froom J, Bartelds AI et al. Acute otitis media in adults: A report from the International Primary Care Network. J. Am. Board Fam. Pract. 6, 333-339 (1993).
2. Faden H, Duffy L, Boeve M. Otitis media: Back to basics. Pediatr. Infect. Dis. J. 7, 1105-1112 (1998).
3. Pelton SI. New concepts in the pathophysiology and management of middle ear disease in childhood. Drugs 52(Suppl. 2), 62-66; discussion 66-67 (1996).
4. Teele DW, Klein JO, Rosner B. Epidemiology of otitis media during the first seven years of life in children in greater Boston: A prospective, cohort study. J. Infect. Dis. 160, 83-94 (1989).
5. Klein JO, Teele DW, Pelton SI. New concepts in otitis media: Results of investigations of the Greater Boston Otitis Media Study Group. Adv. Pediatr. 39, 127-156 (1992).
6. Hoberman A, Marchant CD, Kaplan SL, Feldman S. Treatment of acute otitis media consensus recommendations. Clin. Pediatr. (Phila.) 41, 373-390 (2002).
7. Dagan R, Barkay G, Leibovitz E, Dreifuss E, Greenberg D. Will reduction of antibiotic use reduce antibiotic resistance? The pneumococcus paradigm. Pediatr. Infect. Dis. J. 25, 981-986 (2006).
8. Giebink GS. The microbiology of otitis media. Pediatr. Infect. Dis. J. 8, S18-S20 (1989).
9. Bluestone CD, Stephenson JS, Martin LM. Ten-year review of otitis media pathogens. Pediatr. Infect. Dis. J. 11, S7-S11 (1992).
10. Block SL. Causative pathogens, antibiotic resistance and therapeutic considerations in acute otitis media. Pediatr. Infect. Dis. J. 16, 449-456 (1997).
11. Jacobs MR, Dagan R, Appelbaum PC, Burch DJ. Prevalence of antimicrobial-resistant pathogens in middle ear fluid: Multinational study of 917 children with acute otitis media. Antimicrob. Agents Chemother. 42, 589-595 (1998). (Pubitemid 28114813)
12. Baquero F. Pneumococcal resistance to b-lactam antibiotics: A global geographic overview. Microb. Drug Resist. 1, 115-120 (1993).
13. Appelbaum PC. Epidemiology and in vitro susceptibility of drug-resistant Streptococcus pneumoniae. Pediatr. Infect. Dis. J. 15, 932-934 (1996).
14. Black S, Shinefield H, Fireman B et al. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Northern California Kaiser Permanente Vaccine Study Center Group. Pediatr. Infect. Dis. J. 19, 187-195 (2000).
15. Fireman B, Black SB, Shinefield HR, Lee J, Lewis E, Ray P. Impact of the pneumococcal conjugate vaccine on otitis media. Pediatr. Infect. Dis. J. 22, 10-16 (2003).
16. Eskola J, Kilpi T, Palmu A et al. Efficay of a pneumococcal conjugate vaccine against acute otitis media. N. Engl. J. Med. 344, 403-409 (2001). First study demonstrating the clinical and bacteriologic efficacy of a pneumococcal conjugate vaccine in reducing the rates of acute otitis media (AOM). (Pubitemid 32128672)
17. Casey J, Pichichero ME. Changes in frequency and pathogens causing acute otitis media in 1995-2003. Pediatr. Infect. Dis. J. 23, 824-828 (2004).
18. 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. 23, 829-833 (2004).
19. Pelton SI, Loughlin AM, Marchant CD. Seven valent pneumococcal conjugate vaccine immunization in two Boston communities. Changes in serotypes and antimicrobial susceptibility among Streptococcus pneumoniae isolates. Pediatr. Infect. Dis. J. 23, 1015-1022 (2004).
20. Porat N, Barkai G, Jacobs MR, Trefler R, Dagan R. 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. 189, 385-392 (2004).
21. 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. 190, 2154-2161 (2004).
22. Pelton SI, Huot H, Finkelstein JA et al. Emergence of 19A as virulent and multidrug resistant pneumococcus in Massachusetts following universal immunization of infants with pneumococcal conjugate vaccine. Pediatr. Infect. Dis. J. 26, 468-472 (2007). Researchers report a significant increase in invasive pneumococcal diseases due to serotype 19A in Massachusetts (USA) 3 years after the introduction of seven-valent pneumococcal conjugate vaccine (PCV7).
23. Pichichero ME, Casey JR. Emergence of a multiresistant serotype 19A pneumococcal strain not included in the 7-valent conjugate vaccine as an otopathogen in children. JAMA 298, 1772-1778 (2007). Describes nine cases of complicated AOM caused by a new genotype of serotype 19A resistant to all US FDA-approved antibiotics for use in children with AOM.
24. Klugman KP, McGee L. Resurgence of the multiresistant pneumococcus in the United States: A commentary. Pediatr. Infect. Dis. J. 26, 473-474 (2007).
25. American Academy of Pediatrics and American Academy of Family Physicians. Clinical Practice Guideline. Subcommittee on Management of Acute Otitis Media. Diagnosis and management of acute otitis media. Pediatrics 113, 1451-1465 (2004). Basic guidelines to be used in the treatment of AOM; introduces for the first time the recommendation for the use of the 'watchful waiting' method in the USA.
26. Faden H, Duffy L, Wasielewski R, Wolf J, Krystofik D, Tung Y. Relationship between nasopharyngeal colonization and the development of otitis media in children. Tonawanda/ Williamsville Pediatrics. J. Infect. Dis. 175, 1440-1445 (1997).
27. Harabuchi Y, Faden H, Yamanaka N, Duffy L, Wolf J, Krystofik D. Nasopharyngeal colonization with nontypeable Haemophilus influenzae and recurrent otitis media. Tonawanda/ Williamsville Pediatrics. J. Infect. Dis. 170, 862-866 (1994).
28. Leach AJ, Boswell JB, Asche V, Nienhuys TG, Mathews JD. Bacterial colonization of the nasopharynx predicts very early onset and persistence of otitis media in Australian aboriginal infants. Pediatr. Infect. Dis. J. 13, 983-989 (1994).
29. Heikkinen T, Thint M, Chonmaitree T. Prevalence of various respiratory viruses in the middle ear during acute otitis media. N. Engl. J. Med. 340, 260-264 (1999). (Pubitemid 29063267)
30. Gungor A, Bluestone CD. Antibiotic theory in otitis media. Curr. Allergy Asthma Rep. 1, 364-372 (2001).
31. Doern GV, Pfaller MA, Kugler K, Freeman J, Jones RN. 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. 27, 764-770 (1998).
32. Dagan R. Clinical significance of resistant organisms in otitis media. Pediatr. Infect. Dis. J. 19, 378-382 (2000).
33. Sagraves R. Increasing antibiotic resistance: Its effect on the therapy for otitis media. J. Pediatr. Health Care 16, 79-85 (2002).
34. Leibovitz E, Raiz S, Piglansly L et al. Resistance pattern of middle ear fluid isolates in acute otitis media recently treated with antibiotics. Pediatr. Infect. Dis. J. 17, 463-469 (1998).
35. Leibovitz E, Dagan R. Otitis media therapy and drug resistance. Part 1: Management principles. Infect. Med. 18, 212-216 (2001). (Pubitemid 32374221)
36. Dagan R, Givon-Lavi N, Shkolnik L, Yagupsky P, Fraser D. Acute otitis media caused by antibiotic-resistant Streptococcus pneumoniae in southern Israel: Implication for immunizing with conjugate vaccines. J. Infect. Dis. 181, 1322-1329 (2000).
37. Leibovitz E. Complicated otitis media and its implications. Vaccine 26S, G16-G19 (2008).
38. Klein JO. Microbiologic efficacy of antibacterial drugs for acute otitis media. Pediatr. Infect. Dis. J. 12, 973-975 (1993).
39. Leibovitz E, Greenberg D, Piglansky L et al. Recurrent acute otitis media occurring within one month from completion of antibiotic therapy: Relationship to the original pathogen. Pediatr. Infect. Dis. J. 22, 209-216 (2003). Established that the etiology of recurrent AOM occurring during a 1-month period after the successful completion of antibiotic treatment for the initial AOM episode is very different than previously thought: New pathogens are recovered in 72% of cases.
40. Hausdorff WP, Yothers G, Dagan R et al. Multinational study of pneumococcal serotypes causing acute otitis media in children. Pediatr. Infect. Dis. J. 21, 1008-1016 (2002).
41. Del Beccaro MA, Mendelman PM, Inglis AF et al. Bacteriology of acute otitis media: A new perspective. J. Pediatr. 120, 81-84 (1992).
42. Pichichero ME, Pichichero CL. Persistent acute otitis media: I. Causative pathogens. Pediatr. Infect. Dis. J. 14, 178-183 (1995).
43. 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. 15, 541-543 (1996).
44. Beekmann SE, Heilmann KP, Richter SS, Garcia-de-Lamas J, Doern GV. Antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and group A b-haemolytic streptococci in 2002-2003. Results of the multinational GRASP Surveillance Program. Int. J. Antimicrob. Agents 25, 148-156 (2005).
45. Doern GV, Jones RN, Pfaller MA, Kugler K. Haemophilus influenzae and Moraxella catarrhalis from patients with community-acquired respiratory tract infections: Antimicrobial susceptibility patterns from the SENTRY antimicrobial Surveillance Program (United States and Canada, 1997). Antimicrob. Agents Chemother. 43, 385-389 (1999).
46. Kilpi T, Herva E, Kaijalainen T, SyrjanenR, Takala AK. Bacteriology of acute otitis media in a cohort of Finnish children followed fro the first two years of life. Pediatr. Infect. Dis. J. 20, 654-662 (2001).
47. Jorgensen JH. Update on mechanisms and prevalence of antimicrobial resistance in Haemophilus influenzae. Clin. Infect. Dis. 14, 1119-1123 (1992).
48. Mendelman PM, Chaffin DO, Stull TL et al. Characterization of nonb-lactamase-mediated ampicillin resistance in Haemophilus influenzae. Antimicrob. Agents Chemother. 25, 747-753 (1984).
49. 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. 9, 39-46 (2003).
50. Kaczmarek FS, Gootz TD, Dib-Hajj F, Shang W, Hallowell S, Cronan M. Genetic and molecular characterization of b-lactamase-negative ampicillin-resistant Haemophilus influenzae with unusually high resistance to ampicillin. Antimicrob. Agents Chemother. 48, 1630-1639 (2004).
51. Murphy TF, Kirkham C. Biofilm formation by nontypeable Haemophilus influenzae: Strain variability, outer membrane antigen expression and role of pili. BMC Microbiol. 2, 7 (2002).
52. Hall-Stoodley L, Hu FZ, Gieseke A, Nistico L. Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media. JAMA 296, 202-211 (2006).
53. Bakaletz LO. Bacterial biofilms in otitis media: Evidence and relevance. Pediatr. Infect. Dis. J. 26, S17-S19 (2007).
54. Bluestone C, Stephenson J, Martin L. Ten-year review of otitis media pathogens. Pediatr. Infect. Dis. J. 11, S7-S11 (1992).
55. Guevara S, Soley C, Arguedas A, Porat N, Dagan R. Seasonal distribution of otitis media pathogens among Costa Rican children. Pediatr. Infect. Dis. J. 27, 12-16 (2008).
56. Broides A, Greenberg D, Givon-Lavi N, Leiberman A, Dagan R, Leibovitz E. Acute otitis media caused by Moraxella catarrhalis: Epidemiologic and clinical characteristics. Presented at: 27th Annual Meeting of the European Society for Paediatric Infectious Diseases. Brussels, Belgium, 8-13 June 2009 (Abstract 586).
57. Valentine E. Bacteriologic study of middle ear infections. J. Infect. Dis. 35, 177-183 (1924).
58. Segal N , Givon-Lavi N, Leibovitz E, Yagupsky P, Leiberman A, Dagan R. Acute otitis media caused by Streptococcus pyogenes in children. Clin. Infect. Dis. 41, 35-41 (2005).
59. Prymula R, Peeters P, Chrobok V et al. Pneumococcal capsular polysaccharide conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and nontypable Haemophilus influenzae: A randomized double-blind efficacy study. Lancet 367, 740-848 (2006). AOM trial using an 11-valent pneumococcal conjugate vaccine with the protein D of Haemophilus influenzae as carrier and showing, in addition to a major decrease in vaccine-type pneumococcal AOM, a 35.3% decrease in AOM associated with H. influenzae.
60. Poehling KA, Lafleur BJ, Szilagyi PG et al. Population-based impact of pneumococcal conjugate vaccine in young children. Pediatrics 114, 755-761 (2004).
61. 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 119, 707-715 (2007).
62. Zhau F, Shefer A, Kong Y, Nuorti P. Trends in acute otitis media-related health care utilization by privately insured young children in the United States, 1997-2004. Pediatrics 121, 253-260 (2008). Reports a much higher than expected decrease in the number of visit to physicians due to otitis media, as a result of the routine use of PCV7, but also possibly due to a decrease in the antibiotic use for AOM and also the implementation of the 'watchful waiting' method
63. Richter SS, Heilmann KP, Dohrn CL, Rishi F, Beekmann SE, Doern GV. Changing epidemiology of antimicrobial-resistant Streptococcus pneumoniae in the United States, 2004-2005. Clin. Infect. Dis. 48, e23-e33 (2009). Shows that in the USA, the penicillin-resistant Streptococcus pneumoniae epidemiology has changed as a result of PCV7 introduction, with the main result being a decrease in the prevalence of isolates highly resistant to penicillin, an increase in the isolates nonsusceptible to erythromycin and no change in the prevalence of multidrug-resistant isolates.
64. Farrell DJ, Klugman KP, Pichichero M. Increased antimicrobial resistance among nonvaccine serotypes of Streptococcus pneumoniae in the pediatric population after the introduction of 7-valent pneumococcal vaccine in the United States. Pediatr. Infect. Dis. J. 26, 123-128 (2007). Describes the shift in antimicrobial resistance among the nonvaccine serotypes of S. pneumoniae following the introduction of PCV7 in the USA, a continuous process that is expected worldwide.
65. Dagan R, Givon-Lavi N, Zamir O et al. Reduction of nasopharyngeal carriage of Streptococcus pneumoniae after administration of a 9-valent pneumococcal conjugate vaccine in toddlers attending day care centers. J. Infect. Dis. 185, 927-936 (2002).
66. Dagan R, Givon-Lavi N, Zamir O, Frazer D. Effect of a nine-valent conjugate vaccine on carriage of antibiotic-resistant Streptococcus pneumoniae in day care centers. Pediatr. Infect. Dis. J. 22, 532-539 (2003).
67. Ghaffar F, Barton T, Lozano J et al. Effect of the 7-valent pneumococcal conjugate vaccine on nasopharyngeal colonization by Streptococcus pneumoniae in the first 2 years of life. Clin. Infect. Dis. 39, 930-938 (2004).
68. Brook I, Grober AE. Bacteriology of spontaneously draining acute otitis media in children before and after the introduction of pneumococcal vaccination. Pediatr. Infect. Dis J. 28, 640-642 (2009).
69. Pelton SI, Loughlin AM, Marchant CD. Seven valent pneumococcal conjugate vaccine immunization in two Boston communities. Changes in serotypes and antimicrobial susceptibility among Streptococcus pneumoniae isolates. Pediatr. Infect. Dis. J. 23, 1015-1022 (2004).
70. Porat N, Barkai G, Jacobs MR, Trefler R, Dagan R. 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. 189, 385-392 (2004).
71. 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. 190, 2154-2161 (2004).
72. Dagan R, Givon-Lavi N, Leibovitz E, Greenberg D, Porat N. Introduction and proliferation of multiresistant Streptococcus pneumoniae serotype 19A clones causing acute otitis media in an unvaccinated population. J. Infect. Dis. 199, 776-785 (2009). Based on data collected in Israel from patients with AOM before the introduction of pneumococcal conjugate vaccines, the authors suggest that the increase in the 19A serotype recovery rates and its antibiotic resistance, occurring in the absence of antipneumococcal immunization with PCV7, was mainly related to antibiotic overuse.
73. 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. 124, 355-367 (1994).
74. Del Mar C, Glasziou P, Hayem M. Are antibiotics indicated as initial treatment for children with acute otitis media? A meta-analysis. Br. Med. J. 314, 1526-1529 (1997). (Pubitemid 27216070)
75. Glasziou PP, Del Mar CB, Hayem M, Sanders SL. Antibiotics for acute otitis media in children. Cochrane Database Syst. Rev. 1, CD000219 (2000).
76. van Buchem FL, Peeters MF, van 't Hof MA. Acute otitis media: A new treatment strategy. Br. Med. J. (Clin. Res. Ed.) 290, 1033-1037 (1985). Basis of the 'watchful waiting' treatment method for AOM, practiced in Holland for more than 20 years.
77. Little P, Gould C, Moore M, Warner G, Dunleavey J, Williamson I. Predictors of poor outcome and benefits from antibiotics in children with acute otitis media: Pragmatic randomised trial. Br. Med. J. 325, 1-6 (2002).
78. Dagan R, McCracken GH Jr. Flaws in design and conduct of clinical trials in acute otitis media. Pediatr. Infec. Dis. J. 21, 894-902 (2002).
79. Wald E. Acute otitis media: More trouble with the evidence. Pediatr. Infect. Dis. J. 22, 103-104 (2003).
80. Pichichero ME, Casey JR. Comparison of study designs for acute otitis media trials. Int. J. Pediatr. Otolaryngol. 72, 737-750 (2008).
81. Pichichero ME, Casey JR. Diagnostic inaccuracy and subject exclusion render placebo and observational studies of acute otitis media inconclusive. Pediatr. Infect. Dis. J. 27, 958-962 (2008).
82. Rovers MM, Glasziou P, Appelman CL et al. Antibiotics for acute otitis media: A meta-analysis with individual patient data. Lancet 368, 1429-1435 (2006).
83. Leibovitz E, Asher E, Piglansky L et al. Is bilateral acute otitis media clinically different than unilateral acute otitis media? Pediatr. Infect. Dis. J. 26, 589-592 (2007).
84. Kaleida PH, Casselbrant ML, Rockette HE et al. Amoxicillin or myringotomy or both for acute otitis media: Results of a randomized clinical trial. Pediatrics 87, 466-474 (1991).
85. Klein JO. The "in vivo sensitivity test" for acute otitis media revisited. Pediatr. Infect. Dis. J. 17, 774-775 (1998).
86. Dagan R, Leibovitz E. Bacterial eradication in the treatment of acute otitis media. Lancet Infect. Dis. 2, 593-604 (2002).
87. 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. 22, 405-413 (2003). The only available study demonstrating the bacteriologic efficacy of the high-dose amoxicillin in the treatment of AOM; it showed that, in cases where the treatment fails, it selects for b-lactamase-producing organisms and provides the answer for the appropriate antibiotic treatment in such cases (a drug stable to b-lactamases).
88. Dagan R, Leibovitz E, Fliss DM et al. Bacteriologic efficacies of oral azithromycin and oral cefaclor in treatment of acute otitis media in infants and young children. Antimicrob. Agents Chemother. 44, 43-50 (2000).
89. Dagan R, Johnson CE, McLinn S et al. Bacteriologic and clinical efficacy of amoxicillin/clavulanate vs. azithromycin in acute otitis media. Pediatr. Infect. Dis. J. 19, 95-104 (2000).
90. Hoberman A, Dagan R, Leibovitz E et al. Large dosage amoxicillin/ clavulanate compared with azithromycin for the treatment of bacterial acute otitis media in children. Pediatr. Infect. Dis. J. 24, 525-532 (2005).
91. Scaglione F. Predicting the clinical efficacy of antibiotics: Toward definitive criteria. Pediatr. Infect. Dis. J. 16(Suppl.), S56-S59 (1997).
92. Weisblum B. Erythromycin resistance by ribosome modification. Antimicrob. Agents Chemother. 39, 577-585 (1995).
93. Leibovitz E, Piglansky L, Raiz S, Press J, Leiberman A, Dagan R. 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. 19, 1040-1045 (2000).
94. Leiberman A, Leibovitz E, Piglansky L et al. The bacteriologic and clinical efficacy of trimethoprim/sulfamethoxazole in the treatment of acute otitis media in children. Pediatr. Infect. Dis. J. 20, 260-264 (2001). (Pubitemid 32240264)
95. Dagan R, Schneider S, Givon-Lavi N et al. Failure to achieve early bacterial eradication increases clinical failure rate in acute otitis media in young children. Pediatr. Infect. Dis. J. 27, 200-206 (2008). Recent double-tympanocentesis study finally demonstrating the relationship between bacterial eradication (by efficacious antibiotic drugs) of otopathogens and clinical improvement at the end of therapy of patients with AOM.
96. Asher E, Dagan R, Greenberg D et al. Persistence of pathogens despite clinical improvement in antibiotic-treated acute otitis media is associated with clinical and bacteriologic relapse. Pediatr. Infect. Dis. J. 27, 296-301 (2008). Demonstrates, in a large number of patients, the relationship between bacterial eradication/or a lack of eradication of the main otopathogens causing AOM and clinical and bacteriologic relapses of AOM.
97. Rodriguez WJ, Schwartz RH. Streptococcus pneumoniae causes otitis media with higher fever more redness of tympanic membrane than Haemophilus influenzae or Moraxella catarrhalis. Pediatr. Infect. Dis. J. 18, 942-944 (1999).
98. Palmu AA, Herva E, Savolainene H et al. Association of clinical signs and symptoms with bacterial findings in acute otitis media. Clin. Infect. Dis. 83, 234-242 (2004).
99. Olson LC, Jackson MA. Only the pneumococccus. Pediatr. Infect. Dis. J. 81, 849-850 (1999).
100. Leibovitz E, Jacobs MR, Dagan R. Haemophilus influenzae: A significant pathogen in acute otitis media. Pediatr. Infect. Dis. J. 23, 1142-1155 (2004).
101. Barkai G, Leibovitz E, Givon-Lavi N, Dagan R. Potential contribution by nontypable Haemophilus influenzae in protracted and recurrent acute otitis media. Pediatr. Infect. Dis. J. 28, 466-471 (2009).
102. Canafax DM, Yuan Z, Chonmaitree T et al. Amoxicillin middle ear fluid penetration and pharmacokinetics in children with acute otitis media. Pediatr. Infect. Dis. J. 17, 149-156 (1998).
103. Pichichero ME, Reed MD. Variations in amoxicillin pharmacokinetic/ pharmacodynamic parameters may explain treatment failures in acute otitis media. Paediatr. Drugs 11, 243-249 (2009).
104. 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. 20, 829-837 (2001). (Pubitemid 32880315)
105. Pichichero ME. A review of evidence supporting the American Academy of Pediatrics recommendation for prescribing cephalosporin antibiotics for penicillin-allergic patients. Pediatrics 115, 1048-1057 (2005).
106. Fenoll A, Gimenez MJ, Robledo O et al. In vitro activity of oral cephalosporins against pediatric isolates of Streptococcus pneumoniae nonsusceptible to penicillin, amoxicillin or erythromycin. J. Chemother. 20, 175-179 (2008).
107. Arguedas A, Emparanza P, Schwartz RH et al. A randomized, multicenter, double blind, double dummy trial of single dose azithromycin versus high dose amoxicillin for treatment of uncomplicated acute otitis media. Pediatr. Infect. Dis. J. 24, 153-161 (2005). (Pubitemid 40250775)
108. Green SM, Rothrock SG. Single-dose intramuscular ceftriaxone for acute otitis media in children. Pediatrics 91, 23-30 (1993).
109. Uhari M, Kontiokari T, Koskela M, Niemela M. Xylitol chewing gum in prevention of acute otitis media: Double blind randomised trial. Br. Med. J. 313, 1180-1183 (1996). (Pubitemid 126752390)
110. Ukari M, Tapiainen T, Kontiokari T. Xylitol in preventing acute otitis media. Vaccine 19, S144-S147 (2000).
111. Hautalahti O, Renko M, TapiainenT, Kontiokari T, Pokka T, Uhari M. Failure of xylitol given three times a day for preventing acute otitis media. Pediatr. Infect. Dis. J. 26, 423-427 (2007).
112. Roos K, Grahn Hakansson E, Holm S. Effect of recolonization with 'interfering' a streptococci on recurrences of acute and secretory otitis media in children: Randomized placebo controlled trials. Br. Med. J. 322, 1-4 (2001).