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최근 4년간 국내 단일 의료기관을 내원한 소아청소년에서 분리된 폐구균의 항생제 감수성 양상 분석

Antibiotics Susceptability of Streptococcus pneumoniae Isolated from Single Tertiary Childrens' Hospital Since 2014 and Choice of Appropriate Empirical Antibiotics

  • 정지원 (울산대학교 의과대학 서울아산병원 소아청소년과) ;
  • 유리나 (울산대학교 의과대학 서울아산병원 소아청소년과) ;
  • 성흥섭 (울산대학교 의과대학 서울아산병원 진단검사의학과) ;
  • 김미나 (울산대학교 의과대학 서울아산병원 진단검사의학과) ;
  • 이진아 (울산대학교 의과대학 서울아산병원 소아청소년과)
  • Jung, Jiwon (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Yoo, Ree Nar (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Sung, Hungseop (Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, Mina (Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Lee, Jina (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine)
  • 투고 : 2018.09.04
  • 심사 : 2018.12.09
  • 발행 : 2019.04.25

초록

목적: 최근 4년간 서울아산병원에 내원한 소아청소년에서 분리된 폐구균의 항생제 감수성 양상을 파악하여, 3차 의료기관 내원 환자에서 발생한 폐구균 감염증에서 적절한 경험적 항균 요법을 제시하고자 하였다. 방법: 2014년 3월부터 2018년 5월까지서울아산병원어린이병원에폐구균감염으로입원하였던 18세미만의환아를대상으로 연령, 성별, 기저질환 및 폐구균의 ${\beta}-lactams$ 및 macrolide 항생제 감수성 양상을 후향적 의무 기록을 통해 조사하였다. Fallon 등이 제시한 Monte Carlo simulation 모델을 이용하여 경구 amoxicillin의 치료 효과를 예측하였다. 결과: 총 63례의 폐구균 감염증이 연구에 포함되었고, 87.3%(55례)는 기저질환이 있는 환아에서 발생하였다. 20.6%(13례)가 혈액(11례)을 포함한 무균성 체액에서 분리된 침습성 감염증이었으며, 폐구균에 의한 뇌수막염은 발생하지 않았다. Amoxicillin, 정주용 penicillin, cefotaxime 및 erythromycin에 대한 내성률은 각각 50.8%, 31.8%, 25.4% 및 95.2%이었으며, amoxicillin과 cefotaxime에 대한 고도 내성률은 각각 23.8% 및 9.5%이었다. Monte Carlo simulation에 의하면 경구용 amoxicillin을 90 mg/kg/day의 용량으로 투여 시 적절한 치료 효과를 기대할 수 있는 amoxicillin MIC 값은 $2.0{\mu}g/mL$ 이하로서 본 연구에서 포함된 비침습성 폐구균의 46.0%가 이 범위에 속하였다. 결론: 최근 4년간 기저질환을 가진 소아환자에서 분리된 폐구균 중 amoxicillin 및 cefotaxime에 고도 내성을 보이는 균주의 비율이 증가하였으며, erythromycin에 대하여 95% 이상 내성이다. 이에 다양한 기저질환을 동반한 고위험군 환아에서 발생한 폐구균 감염증에서 신중한 경험적 항생제 선택이 필요하겠으며, 침습 감염 및 내성 확산 방지를 위한 적절한 폐구균 백신 접종이 필수적이다.

Purpose: We investigated the distribution and antimicrobial resistance of pneumococcal isolates from hospitalized children at Asan Medical Center for recent 4 years, and aimed to recommend proper choice of empirical antibiotics for pneumococcal infection. Methods: From March 2014 to May 2018, children admitted to Asan Medical Center Childrens' Hospital with pneumococcal infection were subjected for evaluation of minimal inhibitory concentration (MIC) for ${\beta}-lactams$ and macrolide antibiotics. Patient's age, underlying disease, gender were retrospectively collected. Using Monte Carlo simulation model and MIC from our study, we predicted the rate of treatment success with amoxicillin treatment. Results: Sixty-three isolates were analyzed including 20.6% (n=13) of invasive isolates, and 79.4% (n=50) of non-invasive isolates; median age were 3.3 years old, and 87.3% of the pneumococcal infections occurred to children with underlying disease. Overall susceptibility rate was 49.2%, 68.2%, and 74.6% for amoxicillin, parenteral penicillin, and cefotaxime respectively. 23.8% and 9.5% of the isolates showed high resistance for amoxicillin, and cefotaxime. Only 4.8% (n=3) were susceptible to erythromycin. Monte Carlo simulation model revealed the likelihood of treatment success was 46.0% at the dosage of 90 mg/kg/day of amoxicillin. Conclusions: Recent pneumococcal isolates from pediatric patients with underlying disease revealed high resistance for amoxicillin and cefotaxime, and high resistance for erythromycin. Prudent choice of antibiotics based on the local data of resistance cannot be emphasized enough, especially in high risk patients with underlying disease, and timely vaccination should be implemented for prevention of the spread of resistant strains.

키워드

참고문헌

  1. Kim KH, Sohn YM, Kang JH, Kim KN, Kim DS, Kim JH, et al. The causative organisms of bacterial meningitis in Korean children, 1986-1995. J Korean Med Sci 1998;13:60-4. https://doi.org/10.3346/jkms.1998.13.1.60
  2. Hausdorff WP, Feikin DR, Klugman KP. Epidemiological differences among pneumococcal serotypes. Lancet Infect Dis 2005;5:83-93. https://doi.org/10.1016/S1473-3099(05)70083-9
  3. Tan TQ. Pediatric invasive pneumococcal disease in the United States in the era of pneumococcal conjugate vaccines. Clin Microbiol Rev 2012;25:409-19. https://doi.org/10.1128/CMR.00018-12
  4. Brandileone MC, Vieira VS, Casagrande ST, Zanella RC, Guerra ML, Bokermann S, et al. Prevalence of serotypes and antimicrobial resistance of Streptococcus pneumoniae strains isolated from Brazilian children with invasive infections. Pneumococcal study group in Brazil for the SIREVA project. Regional system for vaccines in Latin America. Microb Drug Resist 1997;3:141-6. https://doi.org/10.1089/mdr.1997.3.141
  5. Mantese OC, Paula A, Almeida VV, Aguiar PA, Wolkers PC, Alvares JR, et al. Prevalence of serotypes and antimicrobial resistance of invasive strains of pneumococcus in children: analysis of 9 years. J Pediatr (Rio J) 2009;85:495-502.
  6. Klugman KP. Pneumococcal resistance to antibiotics. Clin Microbiol Rev 1990;3:171-96. https://doi.org/10.1128/CMR.3.2.171
  7. Song EK, Lee JH, Kim NH, Lee JA, Kim DH, Park KW, et al. Epidemiology and clinical features of invasive pneumococcal infections in children. Korean J Pediatr Infect Dis 2005;12:140-8. https://doi.org/10.14776/kjpid.2005.12.2.140
  8. Doern GV, Richter SS, Miller A, Miller N, Rice C, Heilmann K, et al. Antimicrobial resistance among Streptococcus pneumoniae in the United States: have we begun to turn the corner on resistance to certain antimicrobial classes? Clin Infect Dis 2005;41:139-48. https://doi.org/10.1086/430906
  9. Song JH, Lee NY, Ichiyama S, Yoshida R, Hirakata Y, Fu W, et al. Spread of drug-resistant Streptococcus pneumoniae in Asian countries: Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study. Clin Infect Dis 1999;28:1206-11. https://doi.org/10.1086/514783
  10. Weinstein MP, Klugman KP, Jones RN. Rationale for revised penicillin susceptibility breakpoints versus Streptococcus pneumoniae: coping with antimicrobial susceptibility in an era of resistance. Clin Infect Dis 2009;48:1596-600. https://doi.org/10.1086/598975
  11. CLSI. Performance standards for antimicrobial susceptibility testing: eighteenth informational supplement. CLSI document M100-S26. Wayne: Clinical and Laboratory Standards Institute, 2008.
  12. Cho EY, Lee H, Choi EH, Kim YJ, Eun BW, Cho YK, et al. Serotype distribution and antibiotic resistance of Streptococcus pneumoniae isolated from invasive infections after optional use of the 7-valent conjugate vaccine in Korea, 2006-2010. Diagn Microbiol Infect Dis 2014;78:481-6. https://doi.org/10.1016/j.diagmicrobio.2013.12.016
  13. Vuori-Holopainen E, Peltola H, Kallio MJ; SE-TU Study Group. Narrow-versus broad-spectrum parenteral anatimicrobials against common infections of childhood: a prospective and randomised comparison between penicillin and cefuroxime. Eur J Pediatr 2000;159:878-84. https://doi.org/10.1007/PL00008360
  14. Paik JY, Choi JH, Cho EY, Oh CE, Lee J, Choi EH, et al. Antibiotics susceptability of Streptococcus pneumoniae isolated from pharynx in healthy Korean children and choice of proper empirical oral antibiotics using pharmacokinetics/pharmacodynamics model. Korean J Pediatr Infect Dis 2011;18:109-16. https://doi.org/10.14776/kjpid.2011.18.2.109
  15. Fallon RM, Kuti JL, Doern GV, Girotto JE, Nicolau DP. Pharmacodynamic target attainment of oral ${\beta}$-lactams for the empiric treatment of acute otitis media in children. Paediatr Drugs 2008;10:329-35. https://doi.org/10.2165/00148581-200810050-00006
  16. Jung YS. Antibiotics resistance of Streptococcus pneumoniae and Enterococcus sp. J Korean Soc Chemother 1993;11:48-55.
  17. Friedland IR, Klugman KP. Antibiotic-resistant pneumococcal disease in South African children. Am J Dis Child 1992;146:920-3.
  18. Pallares R, Linares J, Vadillo M, Cabellos C, Manresa F, Viladrich PF, et al. Resistance to penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain. N Engl J Med 1995;333:474-80. https://doi.org/10.1056/NEJM199508243330802
  19. Song JH, Jung SI, Ki HK, Shin MH, Ko KS, Son JS, et al. Clinical outcomes of pneumococcal pneumonia caused by antibiotic-resistant strains in Asian countries: a study by the Asian Network for Surveillance of Resistant Pathogens. Clin Infect Dis 2004;38:1570-8. https://doi.org/10.1086/420821
  20. 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
  21. Yum HY. Antibiotics for bacterial pneumonia in children. Korean J Pediatr 2009;52:283-8. https://doi.org/10.3345/kjp.2009.52.3.283
  22. Torumkuney D, Chaiwarith R, Reechaipichitkul W, Malatham K, Chareonphaibul V, Rodrigues C, et al. Results from the survey of antibiotic resistance (SOAR) 2012-14 in Thailand, India, South Korea and Singapore. J Antimicrob Chemother 2016;71 Suppl 1:i3-19. https://doi.org/10.1093/jac/dkw073
  23. Cho EY, Kang HM, Lee J, Kang JH, Choi EH, Lee HJ. Changes in serotype distribution and antibiotic resistance of nasopharyngeal isolates of Streptococcus pneumoniae from children in Korea, after optional use of the 7-valent conjugate vaccine. J Korean Med Sci 2012;27:716-22. https://doi.org/10.3346/jkms.2012.27.7.716
  24. 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
  25. Song JH, Chang HH, Suh JY, Ko KS, Jung SI, Oh WS, et al. Macrolide resistance and genotypic characterization of Streptococcus pneumoniae in Asian countries: a study of the Asian Network for Surveillance of Resistant Pathogens (ANSORP). J Antimicrob Chemother 2004;53:457-63. https://doi.org/10.1093/jac/dkh118
  26. Robinson KA, Baughman W, Rothrock G, Barrett NL, Pass M, Lexau C, et al. Epidemiology of invasive Streptococcus pneumoniae infections in the United States, 1995-1998: opportunities for prevention in the conjugate vaccine era. JAMA 2001;285:1729-35. https://doi.org/10.1001/jama.285.13.1729
  27. Hicks LA, Harrison LH, Flannery B, Hadler JL, Schaffner W, Craig AS, et al. Incidence of pneumococcal disease due to non-pneumococcal conjugate vaccine (PCV7) serotypes in the United States during the era of widespread PCV7 vaccination, 1998-2004. J Infect Dis 2007;196:1346-54. https://doi.org/10.1086/521626
  28. Moore MR, Whitney CG. Emergence of nonvaccine serotypes following introduction of pneumococcal conjugate vaccine: cause and effect? Clin Infect Dis 2008;46:183-5. https://doi.org/10.1086/524661
  29. Yun KW, Choi EH, Lee HJ, Kang JH, Kim KH, Kim DS, et al. Genetic structures of invasive Streptococcus pneumoniae isolates from Korean children obtained between 1995 and 2013. BMC Infect Dis 2018;18:268. https://doi.org/10.1186/s12879-018-3177-7
  30. Kim SH, Bae IK, Park D, Lee K, Kim NY, Song SA, et al. Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae isolates causing invasive and noninvasive pneumococcal diseases in Korea from 2008 to 2014. Biomed Res Int 2016;2016:6950482. https://doi.org/10.1155/2016/6950482