DOI QR코드

DOI QR Code

항생제 사용량 변화에 따른 그람음성균주의 항생제 내성률의 변화 양상

The Impact of the Antibiotic Burden on the Selection of its Resistance among Gram Negative Bacteria Isolated from Children

  • 김서희 (울산대학교 의과대학 서울아산병원 소아청소년과) ;
  • 유리나 (울산대학교 의과대학 서울아산병원 소아청소년과) ;
  • 이진아 (울산대학교 의과대학 서울아산병원 소아청소년과)
  • Kim, Seohee (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Yoo, Reenar (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Lee, Jina (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine)
  • 투고 : 2015.07.12
  • 심사 : 2015.09.09
  • 발행 : 2015.12.25

초록

목적: 국내 소아 그람음성균혈증에서 항생제 내성변화 및 항생제 사용량과의 관계를 분석하였다. 방법: 최근 10년간 18세 이하 입원 환자의 혈액에서 분리된 그람음성균의 항생제 내성률 변화 및 항생제 사용량과의 관계를 분석하였다. 결과: 폐렴막대균, 대장균, 녹농균, 아시네토박터 바우마니의 분리율은 연간 혈액배양 1,000건당 각각 4.6례, 3.5례, 3.4례 및 2.2례였다. 폐렴막대균에서 광범위 세팔로스포린에 대한 내성변화는 없었으나 2010년부터 카바페넴 내성 폐렴막대균이 동정된 후 점차 빈도가 증가하였다. 대장균의 광범위 세팔로스포린 내성이 10%에서 50%로 아시네토박터 바우마니의 카바페넴 내성이 11%에서 71%로 크게 증가하였다(P for trend <0.01). 녹농균은 여러 항생제에 높은 내성을 보였으나 유의한 내성변화를 보이지 않았다. 대장균의 cefepime 내성과 cefepime 사용량 사이에 유의한 양의 상관관계를 보였다(r=0.900, P=0.037). 결론: 국내 소아에서 발생한 그람음성균 균혈증 분석시 카바페넴 및 광범위 세팔로스포린 내성이 증가하였고 일부에서 항생제 사용량과의 관련성을 확인하였다. 이는 원내 경험적 항생제 결정시 중요한 고려 사항이며 추후에도 지속적인 원내 항생제 사용량 및 내성률에 대한 감시가 필요하겠다.

Purpose: We investigated trends in antibiotic pressure and the antibiotic susceptibility of gram negative bacteria isolated from Korean children over 10 consecutive years. Methods: From January 2004 to December 2013, the antibiotic susceptibility of Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii blood isolates obtained from children <18 years of age was determined according to the 2009 Clinical and Laboratory Standards Institute guidelines. Antibiotic consumption data were also analyzed. Results: The prevalence of K. pneumoniae, E. coli, P. aeruginosa, and A. baumannii bacteremia was 4.6, 3.5, 3.4, and 2.2 cases/1,000 blood cultures/year, respectively. In K. pneumoniae, resistance to the third and fourth cephalosporin did not increase significantly. However, carbapenem-resistant K. pneumoniae first appeared in 2010, and the resistance rate increased to 9% between 2012 and 2013. Resistance to 3rd and 4th cephalosporin increased from 10% to 50% in E. coli, and resistance to carbapenem rose abruptly from 11% to 71% in A. baumannii (P for trend <0.01). However, such an increase of resistance was not observed in P. aeruginosa. There is a positive correlation between the resistance rate of cefepime in E. coli and the consumption of cefepime (r=0.900, P=0.037). Conclusion: The significant burden of antibiotic consumption and the high prevalence of antibiotic resistance to gram negative pathogen isolated from bacteremic children were observed. Empirical antibiotics should be wisely selected, and continued efforts to decrease the overall antibiotic pressure are mandatory, especially in highly resistant situations.

키워드

참고문헌

  1. Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006;34:1589-96. https://doi.org/10.1097/01.CCM.0000217961.75225.E9
  2. Hartman ME, Linde-Zwirble WT, Angus DC, Watson RS. Trends in the epidemiology of pediatric severe sepsis. Pediatr Crit Care Med 2013;14:686-93. https://doi.org/10.1097/PCC.0b013e3182917fad
  3. Kang CI, Kim SH, Park WB, Lee KD, Kim HB, Kim EC, et al. Bloodstream infections caused by antibiotic-resistant gram-negative bacilli: risk factors for mortality and impact of inappropriate initial antimicrobial therapy on outcome. Antimicrob Agents Chemother 2005;49:760-6. https://doi.org/10.1128/AAC.49.2.760-766.2005
  4. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013;41:580-637. https://doi.org/10.1097/CCM.0b013e31827e83af
  5. Kim NH, Hwang JH, Song KH, Choe PG, Park WB, Kim ES, et al. Changes in antimicrobial susceptibility of blood isolates in a university hospital in South Korea, 1998-2010. Infect Chemother 2012;44:275-81. https://doi.org/10.3947/ic.2012.44.4.275
  6. Kang SH, Kim YR. Characteristics of microorganisms isolated from blood cultures at a university hospital located in an island region during 2003-2007. Korean J Clin Microbiol 2008;11:11-7. https://doi.org/10.5145/KJCM.2008.11.1.11
  7. Kim SY, Lim G, Kim MJ, Suh JT, Lee HJ. Trends in five-year blood cultures of patients at a university hospital (2003-2007). Korean J Clin Microbiol 2009;12:163-8. https://doi.org/10.5145/KJCM.2009.12.4.163
  8. Ko EY, Kang HJ, Kwon HJ, Choi UY, Lee JW, Lee DG, et al. Clinical investigation of bacteremia in children with hematooncologic diseases. Infect Chemother 2011;43:191-7. https://doi.org/10.3947/ic.2011.43.2.191
  9. Kang JE, Seok JY, Yun KW, Kang HJ, Choi EH, Park KD, et al. Etiological agents in bacteremia of children with hematooncologic diseases (2006-2010): A single center study. Korean J Pediatr Infect Dis 2012;19:131-40. https://doi.org/10.14776/kjpid.2012.19.3.131
  10. Urbanek K, Kolar M, Loveckova Y, Strojil J, Santava L. Influence of third-generation cephalosporin utilization on the occurrence of ESBL-positive Klebsiella pneumoniae strains. J Clin Pharm Ther 2007;32:403-8. https://doi.org/10.1111/j.1365-2710.2007.00836.x
  11. Chaouch C, Hassairi A, Riba M, Boujaafar N. Association between bacterial resistance and antimicrobial consumption. Ann Biol Clin (Paris) 2014;72:555-60.
  12. Sedlakova MH, Urbanek K, Vojtova V, Suchankova H, Imwensi P, Kolar M. Antibiotic consumption and its influence on the resistance in Enterobacteriaceae. BMC Res Notes 2014;7:454. https://doi.org/10.1186/1756-0500-7-454
  13. Asensio A, Alvarez-Espejo T, Fernandez-Crehuet J, Ramos A, Vaque-Rafart J, Bishopberger C, et al. Trends in yearly prevalence of third-generation cephalosporin and fluoroquinolone resistant Enterobacteriaceae infections and antimicrobial use in Spanish hospitals, Spain, 1999 to 2010. Euro Surveill 2011;16
  14. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing: Nineteenth Informational Supplement. M100-S19 2009;Vol. 29 No. 3
  15. Kim YK, Pai H, Lee HJ, Park SE, Choi EH, Kim J, et al. Bloodstream infections by extended-spectrum beta-lactamaseproducing Escherichia coli and Klebsiella pneumoniae in children: epidemiology and clinical outcome. Antimicrob Agents Chemother 2002;46:1481-91. https://doi.org/10.1128/AAC.46.5.1481-1491.2002
  16. Schwaber MJ, Navon-Venezia S, Kaye KS, Ben-Ami R, Schwartz D, Carmeli Y. Clinical and economic impact of bacteremia with extended-spectrum beta-lactamase-producing Enterobacteriaceae. Antimicrob Agents Chemother 2006;50:1257-62. https://doi.org/10.1128/AAC.50.4.1257-1262.2006
  17. Leibovici L, Shraga I, Drucker M, Konigsberger H, Samra Z, Pitlik SD. The benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection. J Intern Med 1998;244:379-86. https://doi.org/10.1046/j.1365-2796.1998.00379.x
  18. Kim HT, Jang HO, Moon JS, Nam SY, Kim DW, Lee CG, et al. Etiology of community-acquired bacteremia in healthy children. Korean J Pediatr 2005;48:716-22.
  19. Kim HJ, Lee NY, Kim S, Shin JH, Kim MN, Kim EC, et al. Characteristics of microorganisms isolated from blood cultures at nine university hospitals in Korea during 2009. Korean J Clin Microbiol 2011;14:48-54. https://doi.org/10.5145/KJCM.2011.14.2.48
  20. Rhee JY, Park YK, Shin JY, Choi JY, Lee MY, Peck KR, et al. KPC-producing extreme drug-resistant Klebsiella pneumoniae isolate from a patient with diabetes mellitus and chronic renal failure on hemodialysis in South Korea. Antimicrob Agents Chemother 2010;54:2278-9. https://doi.org/10.1128/AAC.00011-10
  21. Yoo JS, Kim HM, Yoo JI, Yang JW, Kim HS, Chung GT, et al. Detection of clonal KPC-2-producing Klebsiella pneumoniae ST258 in Korea during nationwide surveillance in 2011. J Med Microbiol 2013;62:1338-42. https://doi.org/10.1099/jmm.0.059428-0
  22. Hong SK, Yong D, Kim K, Hong SS, Hong SG, Khosbayar T, et al. First outbreak of KPC-2-producing Klebsiella pneumoniae sequence type 258 in a hospital in South Korea. J Clin Microbiol 2013;51:3877-9. https://doi.org/10.1128/JCM.01730-13
  23. Decousser JW, Lamy B, Pina P, Allouch PY. Trends in antibiotic susceptibility of bloodstream pathogens in hospitalized patients in France, 1996 to 2007. Diagn Microbiol Infect Dis 2010;66:292-300. https://doi.org/10.1016/j.diagmicrobio.2009.10.007
  24. Lee J, Oh CE, Choi EH, Lee HJ. The impact of the increased use of piperacillin/tazobactam on the selection of antibiotic resistance among invasive Escherichia coli and Klebsiella pneumoniae isolates. Int J Infect Dis 2013;17:e638-43. https://doi.org/10.1016/j.ijid.2013.01.030
  25. Yong D, Shin HB, Kim YK, Cho J, Lee WG, Ha GY, et al. Increase in the prevalence of carbapenem-resistant Acinetobacter isolates and ampicillin-resistant non-typhoidal Salmonella species in Korea: a KONSAR study conducted in 2011. Infect Chemother 2014;46:84-93. https://doi.org/10.3947/ic.2014.46.2.84
  26. Jung SI, Park KH, Kwon KT, Ko KS, Oh WS, Chung DR, et al. Relationship between beta-lactam antmicrobial use and antimicrobial resistance in Klebsiella pneumoniae clinical isolates at 5 tertiary hospitals in Korea. Infect Chemother 2007;39:189-95.
  27. Hsueh PR, Chen WH, Luh KT. Relationships between antimicrobial use and antimicrobial resistance in gramnegative bacteria causing nosocomial infections from 1991- 2003 at a university hospital in Taiwan. Int J Antimicrob Agents 2005;26:463-72. https://doi.org/10.1016/j.ijantimicag.2005.08.016
  28. Kim BN. Overview of antibiotic use in Korea. Infect Chemother 2012;44:250-62. https://doi.org/10.3947/ic.2012.44.4.250
  29. Park S, Chae SM. Quality assessment of outpatient antibiotic consumptions in Korea compared with other countries. Yakhak Hoeji 2014;58:200-7.
  30. Lee J, Pai H, Kim YK, Kim NH, Eun BW, Kang HJ, et al. Control of extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in a children's hospital by changing antimicrobial agent usage policy. J Antimicrob Chemother 2007;60:629-37. https://doi.org/10.1093/jac/dkm225
  31. Du B, Chen D, Liu D, Long Y, Shi Y, Wang H, et al. Restriction of third-generation cephalosporin use decreases infectionrelated mortality. Crit Care Med 2003;31:1088-93. https://doi.org/10.1097/01.CCM.0000059315.07526.DA
  32. Meyer E, Lapatschek M, Bechtold A, Schwarzkopf G, Gastmeier P, Schwab F. Impact of restriction of third generation cephalosporins on the burden of third generation cephalosporin resistant K. pneumoniae and E. coli in an ICU. Intensive Care Med 2009;35:862-70. https://doi.org/10.1007/s00134-008-1355-6
  33. Sistanizad M, Kouchek M, Miri M, Goharani R, Solouki M, Ayazkhoo L, et al. Carbapenem restriction and its effect on bacterial resistance in an intensive care unit of a teaching hospital. Iran J Pharm Res 2013;12:503-9.
  34. Ntagiopoulos PG, Paramythiotou E, Antoniadou A, Giamarellou H, Karabinis A. Impact of an antibiotic restriction policy on the antibiotic resistance patterns of gram-negative microorganisms in an intensive care unit in Greece. Int J Antimicrob Agents 2007;30:360-5. https://doi.org/10.1016/j.ijantimicag.2007.05.012
  35. de Araujo OR, da Silva DC, Diegues AR, Arkader R, Cabral EA, Afonso MR, et al. Cefepime restriction improves gramnegative overall resistance patterns in neonatal intensive care unit. Braz J Infect Dis 2007;11:277-80. https://doi.org/10.1590/S1413-86702007000200022

피인용 문헌

  1. Antibiotic Sensitivity Patterns in Children with Urinary Tract Infection: Retrospective Study Over 8 Years in a Single Center vol.23, pp.1, 2015, https://doi.org/10.3339/jkspn.2019.23.1.22
  2. A TEN-YEAR ANALYSIS OF CHANGES IN THE SENSITIVITY OF THE LEADING UROPATHOGEN TO ANTIBACTERIAL AGENTS IN CHILDREN WITH URINARY TRACT INFECTION IN THE NEPHROLOGY DEPARTMENT vol.73, pp.7, 2020, https://doi.org/10.36740/wlek202007110