Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Emergence of macrolide resistance and clinical use of macrolide antimicrobials in children

Macrolide계 항균제 내성 출현과 소아에서의 임상적 적용

  • Choi, Eun Hwa (Department of Pediatrics, Seoul National University College of Medicine)
  • 최은화 (서울대학교 의과대학 소아과학교실)
  • Received : 2008.08.28
  • Accepted : 2008.09.05
  • Published : 2008.10.15
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Abstract

Macrolide antimicrobial agents including erythromycin, roxithromycin, clarithromycin, and azithromycin are commonly used in the treatment of respiratory tract infections in children. Newer macrolides that have structural modifications of older drug erythromycin show improved change in the spectrum of activity, dosing, and administration. However, recent studies reported that increasing use of macrolide antibiotics is the main force driving the development of macrolide resistance in streptococci. In particular, azithromycin use is more likely to select for macrolide resistance with Streptococcus pneumoniae than is clarithromycin use, a possible reflection of its much longer half life. Recently, erythromycin resistance rates of S. pneumoniae and Streptococcus pyogenes are rapidly increasing in Korea. Two main mechanisms of acquired macrolide resistance have been described, altered binding site on the bacterial ribosome encoded by the ermB gene and active macrolide efflux pump encoded by the mef gene. Relationship between the susceptibility of S. pneumoniae and the response to macrolides has been shown in studies of acute otitis media, but less clear in cases of pneumonia. This article reviews the spectrum of activity, pharmacokinetic properties, mechanisms of action and resistance, and clinical implication of resistance on the treatment of respiratory tract infections in children.

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References

  1. Klein JO. History of macrolide use in pediatrics. Pediatr Infect Dis J 1997;16:427-31 https://doi.org/10.1097/00006454-199704000-00025
  2. Sturgill MG, Rapp RP. Clarithromycin: review of a new macrolide antibiotic with improved microbiologic spectrum and favorable pharmacokinetic and adverse effect profiles. Ann Pharmacother 1992;26:1099-108 https://doi.org/10.1177/106002809202600912
  3. Piscitelli SC, Danziger LH, Rodvold KA. Clarithromycin and azithromycin: new macrolide antibiotics. Clin Pharm 1992; 11:137-52
  4. Hansen LH, Mauvais P, Douthwaite S. The macrolideketolide antibiotic binding site is formed by structures in domains II and V of 23S ribosomal RNA. Mol Microbiol 1999;31:623-31 https://doi.org/10.1046/j.1365-2958.1999.01202.x
  5. Ballow CH, Amsden GW. Azithromycin: the first azalide antibiotic. Ann Pharmacother 1992;26:1253-61 https://doi.org/10.1177/106002809202601014
  6. Zuckerman JM. Macrolide and ketolides: azithromycin, clarithromycin, telithromycin. Infect Dis Clin N Am 2004;18:621- 49 https://doi.org/10.1016/j.idc.2004.04.010
  7. National Committee for Clincal Laboratory Standards (NCCLS). Performance standards for antimicrobial susceptibility testing, 18th ed. NCCLS document M100S18. Wayne, PA:NCCLS, 2008
  8. Hardy DJ, Swanson RN, Rode RA, Marsh K, Shipkowitz NL, Clement JJ. Enhancement of the in vitro and in vivo activities of clarithromycin against Haemophilus influenzae by 14-hydroxy-clarithromycin, its major metabolite in humans. Antimicrob Agents Chemother 1990;34:1407-13 https://doi.org/10.1128/AAC.34.7.1407
  9. Douthwaite S, Hansen LH, Mauvais P. Macrolide-ketolide inhibition of MLS-resistant ribosomes is improved by alternative drug interaction with domain II of 23S rRNA. Mol Microbiol 2000;36:183-93 https://doi.org/10.1046/j.1365-2958.2000.01841.x
  10. Leclercq R, Courvalin P. Bacterial resistance to macrolide, lincosamide, and streptogramin antibiotics by target modification. Antimicrob Agents Chemother 1991;35:1267-72 https://doi.org/10.1128/AAC.35.7.1267
  11. Malhotra-Kumar S, Lammens C, Coenen S, Van Herck K, Goossens H. Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: a randomised, double-blind, placebo-controlled study. Lancet 2007;10;369:482-90
  12. Stephens DS, Zughaier SM, Whitney CG, Baughman WS, Barker L, Gay K, et al. Incidence of macrolide resistance in Streptococcus pneumoniae after introduction of the pneumococcal conjugate vaccine: population-based assessment. Lancet 2005;365:855-63 https://doi.org/10.1016/S0140-6736(05)71043-6
  13. Hyde TB, Gay K, Stephens DS, Vugia DJ, Pass M, Johnson S, et al. Macrolide resistance among invasive Streptococcus pneumoniae isolates. JAMA 2001;286:1857-62 https://doi.org/10.1001/jama.286.15.1857
  14. Doern GV. Antimicrobial use and the emergence of antimicrobial resistance with Streptococcus pneumoniae in the United States. Clin Infect Dis 2001;33(S):S187-92 https://doi.org/10.1086/321812
  15. Perez-Trallero E, Fernandez-Mazarrasa C, Garcia-Rey C, Bouza E, Aguilar L, Garcia-de-Lomas J, et al. Antimicrobial susceptibilities of 1,684 Streptococcus pneumoniae and 2,039 Streptococcus pyogenes isolates and their ecological relationships: results of a 1-year (1998-1999) multicenter surveillance study in Spain. Antimicrob Agents Chemother 2001;45:3334-40 https://doi.org/10.1128/AAC.45.12.3334-3340.2001
  16. Song JH, Jung SI, Ko KS, Kim NY, Son JS, Chang HH, et al. High prevalence of antimicrobial resistance among clinical Streptococcus pneumoniae isolates in Asia (an ANSORP study). Antimicrob Agents Chemother 2004;48:2101-7 https://doi.org/10.1128/AAC.48.6.2101-2107.2004
  17. Lee HJ, Park JY, Jang SH, Kim JH, Kim EC, Choi KW. High incidence of resistance to multiple antimicrobials in clinical isolates of Streptococcus pneumoniae from a university hospital in Korea. Clin Infect Dis 1995;20:826-35 https://doi.org/10.1093/clinids/20.4.826
  18. Choi EH, Kim SH, Eun BW, Kim SJ, Kim NH, Lee J, et al. Streptococcus pneumoniae serotype 19A in children, South Korea. Emerg Infect Dis 2008;14:275-81 https://doi.org/10.3201/eid1402.070807
  19. Lee TJ, Chun JK, Choi KM, Yong DE, Lee KW, Kim DS. Trends in serotype distribution of clinical isolates of Streptococcus pneumoniae: A single center experience from 2001 to 2006. Korean J Pediatr Infect Dis 2006;13:115-23 https://doi.org/10.14776/kjpid.2006.13.2.115
  20. Dagan R, Johnson CE, McLinn S, Abughali N, Feris J, Leibovitz E, et al. Bacteriologic and clinical fficacy of amoxicillin/ clavulanate vs. azithromycin in acute otitis media. Pediatr Infect Dis J 2000;19:95-104 https://doi.org/10.1097/00006454-200002000-00002
  21. Dagan R, Leibovitz E, Leiberman A, Yagupsky P. Clinical significance of antibiotic resistance in acute otitis media and implication of antibiotic treatment on carriage and spread of resistant organisms. Pediatr Infect Dis J 2000;19:S57-65 https://doi.org/10.1097/00006454-200005001-00009
  22. American Academy of Pediatrics and American Academy of Family Physicians, Subcommittee on Management of Acute Otitis Media. Diagnosis and management of acute otitis media. Pediatrics 2004;113:1451-65 https://doi.org/10.1542/peds.113.5.1451
  23. Kogan R, Martinez MA, Rubilar L, Paya E, Quevedo I, Puppo H. Comparative randomized trial of azithromycin versus erythromycin and amoxicillin for treatment of community- acquired pneumonia in children. Pediatr Pulmonol 2003;35:91-8 https://doi.org/10.1002/ppul.10180
  24. Plouffe J, Schwartz DB, Kolokathis A, Sherman BW, Arnow PM, Gezon JA, et al. Clinical efficacy of intravenous followed by oral azithromycin monotherapy in hospitalized patients with community-acquired pneumonia. The Azithromycin Intravenous Clinical Trials Group. Antimicrob Agents Chemother 2000;44:1796-802 https://doi.org/10.1128/AAC.44.7.1796-1802.2000
  25. Kelley MA, Weber DJ, Gilligan P, Cohen MS. Breakthrough pneumococcal bacteremia in patients being treated with azithromycin and clarithromycin. Clin Infect Dis 2000;31: 1008-11 https://doi.org/10.1086/318157
  26. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC. Infectious Diseases Society of America/ American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44S2:S27-72 https://doi.org/10.1086/511159
  27. Seppala H, Nissinen A, Yu Q, Huovinen P. Three different phenotypes of erythromycin-resistant Streptococcus pyogenes in Finland. J Antimicrob Chemother 1993;32:885-91 https://doi.org/10.1093/jac/32.6.885
  28. Borzani M, Luca MD, Varotto F. A survey of susceptibility to erythromycin amongst Streptococcus pyogenes isolates in Italy. J Antimicrob Chemother 1997;40:457-8 https://doi.org/10.1093/jac/40.3.457
  29. De Azavedo JC, Yeung RH, Bast DJ, Duncan CL, Borgia SB, Low DE. Prevalence and mechanisms of macrolide resistance in clinical isolates of group A streptococci from Ontario, Canada. Antimicrob Agents Chemother 1999;43:2144-7
  30. Richter SS, Heilmann KP, Beekmann SE, Miller NJ, Miller AL, Rice CL, et al. Macrolide-resistant Streptococcus pyogenes in the United States, 2002-2003. Clin Infect Dis 2005; 41:599-608 https://doi.org/10.1086/432473
  31. Jung HS, Park SE, Lee HJ, Kim EC, Kim JH. Clinical features of infections caused by Streptococcus pyogenes in children and their antimicrobial susceptibility. Korean J Infect Dis 1998;30:419-25 https://doi.org/10.1080/00365549850160756
  32. Koh EH, Maeng KY, Kim S, Lee NY. Antibiotic susceptibility of Streptococcus pyogenes and association of erythromycin resistance phenotype with resistance to tetracycline. Korean J Lab Med 2004;24:297-300
  33. Kim YH, Cha SH, Ma SH, Kim SK, Lee YH. Antibiotic sensitivity test of Streptococcus pyogenes obtained in patients with streptococcal infections, 2000. Korean J Pediatr Infect Dis 2002;9:79-84
  34. Uh Y, Jang IH, Park JS, Kwon OG, Yoon KJ. Erythromycin resistance phenotype of Streptococcus pyogenes. Korean J Clin Microbiol 1999;2:131-4
  35. Yoon KJ, Uh Young, Hwang GY, Jang IH, Lee MK. Distributions of macrolide-lincosamide-streptogramin (MLS) resistance types in $\beta$-hemolytic streptococci. Korean J Clin Microbiol 2001;4:16-21
  36. Nakae M, Murai T, Kaneko Y, Mitsuhashi S. Drug resistance in Streptococcus pyogenes isolated in Japan (1974- 1975). Antimicrob Agents Chemother 1977;12:427-8 https://doi.org/10.1128/AAC.12.3.427
  37. Bass JW, Weisse ME, Plymyer MR, Murphy S, Eberly BJ. Decline of erythromycin resistance of group A beta-hemolytic streptococci in Japan. Arch Pediatr Adolesc Med 1994; 148:67-71 https://doi.org/10.1001/archpedi.1994.02170010069016
  38. Koo HK, Baek SC, Ma SH, Lee HJ, Cha SH. Trends of the Incidence of Erythromycin-Resistant Group A Streptococci in Korea from 1998 through 2000. Infection and Chemother 2004;36:75-82
  39. Matsuoka M, Narita M, Okazaki N, Ohya H, Yamazaki T, Ouchi K, et al. Characterization and molecular analysis of macrolideresistant Mycoplasma pneumoniae clinical isolates obtained in Japan. Antimicrob Agents Chemother 2004;48: 462-30 https://doi.org/10.1128/AAC.48.12.4624-4630.2004
  40. Waites KB. New concepts of Mycoplasma pneumoniae infections in children. Pediatr Pulmonol 2003;36:267-78 https://doi.org/10.1002/ppul.10346
  41. Kastner U, Guggenbichler JP. Influence of macrolide antibiotics on promotion of resistance in the oral flora of children. Infection 2001;29:251-6 https://doi.org/10.1007/s15010-001-1072-3

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