Pediatric Infection and Vaccine

  • 제27권3호
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  • Pages.147-157
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  • 2020
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  • 2384-1079(pISSN)
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  • 2384-1087(eISSN)
대한소아감염학회 (The Korean Society of Pediatric Infectious Diseases)
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최근 5년간 국내 소아청소년에서 분리된 Haemophilus influenzae의 항생제 감수성 분석

Trend of Antibiotic Susceptibility of Haemophilus influenzae Isolated from Children, 2014-2019

  • 이은택 (울산의대 서울아산병원 소아청소년과) ;
  • 박세라 (울산의대 서울아산병원 소아청소년과) ;
  • 김미나 (울산의대 서울아산병원 진단검사의학과) ;
  • 이진아 (울산의대 서울아산병원 소아청소년과)
  • Lee, Euntaek (Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Park, Sera (Department of Pediatrics, 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 : 2020.09.10
  • 심사 : 2020.10.27
  • 발행 : 2020.12.25
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초록

목적: 최근 β-lactam 계 항생제에 대한 내성을 보이는 Haemophilus influenzae가 증가하고 있다. 본 연구는 최근 5년간 서울아산병원 어린이 병원에서 분리된 H. influenzae 균주의 항생제 내성 양상을 분석하고자 한다. 방법: 2014년 3월부터 2019년 4월까지 서울아산병원 어린이병원을 내원한 18세 미만의 소아청소년 환자의 임상 검체에서 분리된 H. influenzae 균주를 대상으로 항생제 내성 양상을 분석하였다. 결과: 최근 5년간 총 69례의 H. influenzae가 분리되었으며 이들 환자의 연령 중앙값은 5.0 (2.8-8.6)세였다. 총 69례 중 3례(4.3%)가 혈액 배양에서 분리되었으며, 66례(95.7%)가 비침습성 균주로서 대부분 호흡기 검체(59례)에서 분리되었다. 항생제 감수성 분포는 ampicillin (AMP) 감수성/amoxicillin-clavulanate (AMC) 감수성 균주 15례(21.7%), AMP 내성/AMC 감수성 21례(30.4%), AMP 내성/AMC 내성 33례(47.8%)였으며, 최근 5년에 걸쳐 AMP 내성/AMC 내성 균주는 지속적으로 증가하는 경향을 보였다 (2014-2015: 42.1% [8/19], 2016-2017: 46.4% [13/28], 2018-2019: 54.5% [12/22], P for trend=0.342). 2014-2015년에 비해 2018-2019년 기간에는 cefuroxime과 ceftriaxone에 대한 내성률은 각각 31.6%에서 77.3% 및 0.0% 에서 59.1% 로 유의하게 증가하였다(P for trend 0.003 및 <0.001). 결론: 최근 국내의 3차 의료기관에 입원한 소아에서 분리되는 H. influenzae 균주는 AMP및 AMC에 대해 모두 내성인 경우가 흔하며, cefuroxime 및 ceftriaxone 에 대한 내성률이 유의하게 증가하였다. 이러한 균주의 내성 기전 분석과 함께 이의 출현과 확산을 최소화하기 위한 노력이 필수적이다.

Purpose: We investigated the trend of antibiotic susceptibility of Haemophilus influenzae over 5 consecutive years. Methods: We analyzed the antibiotic susceptibility of H. influenzae isolated from children aged <18 years, who were admitted to the Asan Medical Center Children's Hospital from March 2014 to April 2019. Antibiotic susceptibility of H. influenzae was determined by the disk diffusion test according to the European Committee on Antimicrobial Susceptibility Testing guidelines. Results: Excluding duplicates, 69 isolates were obtained over the past 5 years. The median age of the patients was 5 years (range, 2.8-8.6 years). The antibiotic susceptibility patterns were as follows: ampicillin (AMP)-susceptible/amoxicillin-clavulanate (AMC)-susceptible (AS/ACS; n=15 [21.7%]), AMP-resistant/AMC-susceptible (AR/ACS; n=21 [30.4%]), and AMP-resistant/AMC-resistant (AR/ACR; n=33 [47.8%]). The prevalence of isolates with AR/ACR phenotype tended to increase from 42.1% in 2014-2015 to 54.5% in 2018-2019 (P=0.342). Compared to 2014-2015, the resistance rates to cefuroxime and ceftriaxone in 2018-2019 increased from 31.6% to 77.3% and from 0.0% to 59.1%, respectively (P=0.003 and P<0.001, respectively). Conclusions: Over the last 5 years, H. influenzae isolates with AR/ACR phenotype and ceftriaxone resistance were frequently observed at our institute. The incidence of resistance to cefuroxime and ceftriaxone has increased significantly.

키워드

참고문헌

  1. Ubukata K, Morozumi M, Sakuma M, Adachi Y, Mokuno E, Tajima T, et al. Genetic characteristics and antibiotic resistance of Haemophilus influenzae isolates from pediatric patients with acute otitis media after introduction of 13-valent pneumococcal conjugate vaccine in Japan. J Infect Chemother 2019;25:720-6. https://doi.org/10.1016/j.jiac.2019.03.019
  2. Van Dyke MK, Pircon JY, Cohen R, Madhi SA, Rosenblüt A, Macias Parra M, et al. Etiology of acute otitis media in children less than 5 years of age: a pooled analysis of 10 similarly designed observational studies. Pediatr Infect Dis J 2017;36:274-81. https://doi.org/10.1097/INF.0000000000001420
  3. Han MS, Jung HJ, Lee HJ, Choi EH. Increasing prevalence of group iii penicillin-binding protein 3 mutations conferring high-level resistance to beta-lactams among nontypeable Haemophilus influenzae isolates from children in Korea. Microb Drug Resist 2019;25:567-76. https://doi.org/10.1089/mdr.2018.0342
  4. Schotte L, Wautier M, Martiny D, Piérard D, Depypere M. Detection of beta-lactamase-negative ampicillin resistance in Haemophilus influenzae in Belgium. Diagn Microbiol Infect Dis 2019;93:243-9. https://doi.org/10.1016/j.diagmicrobio.2018.10.009
  5. Ben-Shimol S, Givon-Lavi N, Leibovitz E, Raiz S, Greenberg D, Dagan R. Impact of widespread introduction of pneumococcal conjugate vaccines on pneumococcal and nonpneumococcal otitis media. Clin Infect Dis 2016;63:611-8. https://doi.org/10.1093/cid/ciw347
  6. Pichichero ME. Ten-year study of the stringently defined otitis-prone child in Rochester, NY. Pediatr Infect Dis J 2016;35:1033-9. https://doi.org/10.1097/INF.0000000000001217
  7. Kovacs E, Sahin-Tóth J, Tóthpal A, van der Linden M, Tirczka T, Dobay O. Co-carriage of Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis among three different age categories of children in Hungary. PLoS One 2020;15:e0229021. https://doi.org/10.1371/journal.pone.0229021
  8. Kakuta R, Yano H, Hidaka H, Kanamori H, Endo S, Ichimura S, et al. Molecular epidemiology of ampicillin-resistant Haemophilus influenzae causing acute otitis media in Japanese infants and young children. Pediatr Infect Dis J 2016;35:501-6. https://doi.org/10.1097/INF.0000000000001066
  9. Tristram S, Jacobs MR, Appelbaum PC. Antimicrobial resistance in Haemophilus influenzae. Clin Microbiol Rev 2007;20:368-89. https://doi.org/10.1128/CMR.00040-06
  10. Ubukata K. Problems associated with high prevalence of multidrug-resistant bacteria in patients with community-acquired infections. J Infect Chemother 2003;9:285-91. https://doi.org/10.1007/s10156-003-0278-y
  11. Vacas-Córdoba M, Cardozo-Espinola C, Puerta-Alcalde P, Cilloniz C, Torres A, Garcia-Vidal C. Empirical treatment of adults with hospital-acquired pneumonia: lights and shadows of the 2016 clinical practice ATS/IDSA guidelines. Rev Esp Quimioter 2017;30 Suppl 1:30-3.
  12. Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections, 1988. Am J Infect Control 1988;16:128-40. https://doi.org/10.1016/0196-6553(88)90053-3
  13. Bae SM, Lee JH, Lee SK, Yu JY, Lee SH, Kang YH. High prevalence of nasal carriage of β-lactamase-negative ampicillin-resistant Haemophilus influenzae in healthy children in Korea. Epidemiol Infect 2013;141:481-9. https://doi.org/10.1017/S0950268812001082
  14. The European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint tables for interpretation of MICs and zone diameters, version 10.0. Vaxjo: EUCAST, 2020.
  15. Kim IS, Ki CS, Kim S, Oh WS, Peck KR, Song JH, et al. Diversity of ampicillin resistance genes and antimicrobial susceptibility patterns in Haemophilus influenzae strains isolated in Korea. Antimicrob Agents Chemother 2007;51:453-60. https://doi.org/10.1128/AAC.00960-06
  16. Bae S, Lee J, Lee J, Kim E, Lee S, Yu J, et al. Antimicrobial resistance in Haemophilus influenzae respiratory tract isolates in Korea: results of a nationwide acute respiratory infections surveillance. Antimicrob Agents Chemother 2010;54:65-71. https://doi.org/10.1128/AAC.00966-09
  17. Park C, Kim KH, Shin NY, Byun JH, Kwon EY, Lee JW, et al. Genetic diversity of the ftsI gene in β-lactamase-nonproducing ampicillin-resistant and β-lactamase-producing amoxicillin-/clavulanic acid-resistant nasopharyngeal Haemophilus influenzae strains isolated from children in South Korea. Microb Drug Resist 2013;19:224-30. https://doi.org/10.1089/mdr.2012.0116
  18. Dabernat H, Delmas C. Epidemiology and evolution of antibiotic resistance of Haemophilus influenzae in children 5 years of age or less in France, 2001-2008: a retrospective database analysis. Eur J Clin Microbiol Infect Dis 2012;31:2745-53. https://doi.org/10.1007/s10096-012-1623-9
  19. Yokota S, Ohkoshi Y, Sato K, Fujii N. High prevalence of beta-lactam-resistant Haemophilus influenzae type b isolates derived from respiratory tract specimens in Japanese patients. Int J Infect Dis 2009;13:584-8. https://doi.org/10.1016/j.ijid.2008.09.017
  20. Thomas E, Guillouzouic A, Juvin ME, Chene AL, Caillon J, Bémer P, et al. Prevalence of Haemophilus influenzae with alteration of PBP 3 sequence over a 1-year period in a French hospital: focus on a clinical failure after ceftriaxone treatment. Diagn Microbiol Infect Dis 2019;93:89-91. https://doi.org/10.1016/j.diagmicrobio.2018.08.013
  21. Ferjani S, Sassi I, Saidani M, Mhiri E, Ghariani A, Boutiba Ben Boubaker I, et al. Polymorphism of ftsI gene in Haemophilus influenzae and emergence of cefotaxime resistance in two Tunisian hospitals. New Microbes New Infect 2020;36:100690. https://doi.org/10.1016/j.nmni.2020.100690
  22. Osaki Y, Sanbongi Y, Ishikawa M, Kataoka H, Suzuki T, Maeda K, et al. Genetic approach to study the relationship between penicillin-binding protein 3 mutations and Haemophilus influenzae beta-lactam resistance by using site-directed mutagenesis and gene recombinants. Antimicrob Agents Chemother 2005;49:2834-9. https://doi.org/10.1128/AAC.49.7.2834-2839.2005
  23. Garcia-Cobos S, Campos J, Lazaro E, Roman F, Cercenado E, Garcia-Rey C, et al. Ampicillin-resistant non-beta-lactamase-producing Haemophilus influenzae in Spain: recent emergence of clonal isolates with increased resistance to cefotaxime and cefixime. Antimicrob Agents Chemother 2007;51:2564-73. https://doi.org/10.1128/AAC.00354-07
  24. Ubukata K, Shibasaki Y, Yamamoto K, Chiba N, Hasegawa K, Takeuchi Y, et al. Association of amino acid substitutions in penicillin-binding protein 3 with beta-lactam resistance in beta-lactamase-negative ampicillin-resistant Haemophilus influenzae. Antimicrob Agents Chemother 2001;45:1693-9. https://doi.org/10.1128/AAC.45.6.1693-1699.2001
  25. Skaare D, Anthonisen IL, Kahlmeter G, Matuschek E, Natås OB, Steinbakk M, et al. Emergence of clonally related multidrug resistant Haemophilus influenzae with penicillin-binding protein 3-mediated resistance to extended-spectrum cephalosporins, Norway, 2006 to 2013. Euro Surveill 2014;19:20986.
  26. Stephen J. Haemophilus influenzae. In: Feigin RD, Cherry JD, editors. Textbook of pediatric infectious diseases. 8th ed. Amsterdam: Elsevier, 2019:1199-1211.
  27. Asbell PA, Sanfilippo CM, Sahm DF, DeCory HH. Trends in antibiotic resistance among ocular microorganisms in the United States from 2009 to 2018. JAMA Ophthalmol 2020;138:439-50. https://doi.org/10.1001/jamaophthalmol.2020.0155
  28. Jung J, Seo E, Yoo RN, Sung H, Lee J. Clinical significance of viral-bacterial codetection among young children with respiratory tract infections: findings of RSV, influenza, adenoviral infections. Medicine (Baltimore) 2020;99:e18504. https://doi.org/10.1097/md.0000000000018504
  29. Manoharan A, Pai R, Shankar V, Thomas K, Lalitha MK. Comparison of disc diffusion & E test methods with agar dilution for antimicrobial susceptibility testing of Haemophilus influenzae. Indian J Med Res 2003.117:81-7.
  30. Barry AL, Fuchs PC, Brown SD. Identification of beta-lactamase-negative, ampicillin-resistant strains of Haemophilus influenzae with four methods and eight media. Antimicrob Agents Chemother 2001;45:1585-8. https://doi.org/10.1128/AAC.45.5.1585-1588.2001
  31. Billal DS, Hotomi M, Yamanaka N. Can the Etest correctly determine the MICs of beta-lactam and cephalosporin antibiotics for beta-lactamase-negative ampicillin-resistant Haemophilus influenzae? Antimicrob Agents Chemother 2007;51:3463-4. https://doi.org/10.1128/AAC.00190-07
  32. Tristram SG. A comparison of Etest, M.I.C.Evaluator strips and CLSI broth microdilution for determining {beta}-lactam antimicrobial susceptibility in Haemophilus influenzae. J Antimicrob Chemother 2008;62:1464-6. https://doi.org/10.1093/jac/dkn365
  33. Skaare D, Lia A, Hannisdal A, Tveten Y, Matuschek E, Kahlmeter G, et al. Haemophilus influenzae with non-beta-lactamase-mediated beta-lactam resistance: easy to find but hard to categorize. J Clin Microbiol 2015;53:3589-95. https://doi.org/10.1128/JCM.01630-15