Etiological agents isolated from blood in children with hemato-oncologic disease (2002-2005)

소아 혈액 종양 환자에서 발생한 균혈증의 원인균(2002-2005년)

  • Kim, So-Hee (Departments of Pediatrics, Seoul National University College of Medicine) ;
  • Lee, Young-Ah (Departments of Pediatrics, Seoul National University College of Medicine) ;
  • Eun, Byung-Wook (Departments of Pediatrics, Seoul National University College of Medicine) ;
  • Kim, Nam-Hee (Departments of Pediatrics, Seoul National University College of Medicine) ;
  • Lee, Jin-A (Departments of Pediatrics, Seoul National University College of Medicine) ;
  • Kang, Hyoung Jin (Cancer Research Institute, Seoul National University College of Medicine) ;
  • Choi, Eun-Hwa (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Shin, Hee Young (Cancer Research Institute, Seoul National University College of Medicine) ;
  • Lee, Hoan-Jong (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Ahn, Hyo Seop (Cancer Research Institute, Seoul National University College of Medicine)
  • 김소희 (서울대학교 의과대학 소아과학교실) ;
  • 이영아 (서울대학교 의과대학 소아과학교실) ;
  • 은병욱 (서울대학교 의과대학 소아과학교실) ;
  • 김남희 (서울대학교 의과대학 소아과학교실) ;
  • 이진아 (서울대학교 의과대학 소아과학교실) ;
  • 강형진 (서울대학교 의과대학 암연구소) ;
  • 최은화 (서울대학교 의과대학 소아과학교실) ;
  • 신희영 (서울대학교 의과대학 암연구소) ;
  • 이환종 (서울대학교 의과대학 소아과학교실) ;
  • 안효섭 (서울대학교 의과대학 암연구소)
  • Received : 2006.10.30
  • Accepted : 2006.12.15
  • Published : 2007.01.15

Abstract

Purpose : This study was performed to identify the etiologic agents and antimicrobial susceptibility patterns of organisms responsible for bloodstream infections in pediatric cancer patients for guidance in empiric antimicrobial therapy. Methods : One hundred and ninety-seven episodes of bloodstream infections that developed in 128 pediatric cancer patients were analyzed, which were identified at the Seoul National University Children's Hospital during a 4 year-period from 2002 to 2005. Results : A total of 214 pathogens was isolated, of which 64.0 percent were gram-negative, 31.3 percent were gram-positive bacteria, and 4.7 percent were fungi. The most common pathogens were Klebsiella spp. (21 percent) and Escherichia coli (16.8 percent), and coagulase-negative staphylococci (CNS, 7.9 percent) and viridans streptococci (7.5 percent) emerged as important pathogens. Neutropenic patients were more often associated with gram-negative bacteria than non-neutropenic patients (67.5 percent vs. 51.1%, P=0.018) and patients with central venous catheters were more often associated with CNS and viridans streptococci than those without. Resistance rates of gram-positive bacteria to penicillin, oxacillin and vancomycin were 83.3 percent, 48.5 percent and 0.5 percent, respectively, and those of gram-negative bacteria to cefotaxime, piperacillin/tazobactam, imipenem, gentamicin and amikacin were 24.1 percent, 17.2 percent, 6.6 percent, 21.6 percent, and 14.2 percent, respectively. Gram-negative bacteremias were more often associated with intensive care than gram-positive bacteremias (26.5 percent vs. 10.3 percent, P=0.016), and patients with catheters were more often associated with intensive care (34.4 percent vs. 10.8 percent, P<0.001) and higher fatality rate (16.7 percent vs. 4.8 percent, P=0.012) than those without. Conclusion : This study revealed that gram-negative bacteria are still a dominant organism in bloodstream infections, especially in neutropenic patients, and confirmed that gram-positive bacteria are emerging as important etiological agents in bloodstream infections of pediatric hemato-oncologic patients.

목 적 : 소아 종양 환자에서 발열이 있는 경우, 즉각적인 경험적 항생제 치료가 필요하기 때문에, 지역이나 병원 내에서 발생한 균혈증의 흔한 원인균과 항생제 감수성에 대한 최근 경향에 대한 정보가 필요하다. 본 연구에서는 4년간 소아 종양 환자에서 분리된 균혈증의 원인균 분포와 이들의 항생제 감수성에 대하여 분석하고자 하였다. 방 법 : 2002년 1월부터 2005년 12월까지 서울대학교 어린이병원 소아 종양 환자 128명 환아에서 발생한 197례의 균혈증과 이들에서 분리된 214균주에 대하여 분석하였다. 결 과 : 총 214균주 중 그람음성균이 64.0%, 그람양성균이 31.3%였으며 진균은 4.7%이었다. 균혈증을 일으킨 가장 흔한 균은 Klebsiella species(21%)와 E. coli(16.8%)였으며, CNS와 viridans streptococci도 7.9%와 7.5%로 분리율이 높았다. 호중구 감소증이 있는 환자군에서 그람음성균이 차지하는 비율이 감소증이 없는 환자군에 비해 높았고(67.5% vs. 51.1%, P=0.018), 균혈증 발생 당시 중심 정맥관을 가진 경우에 CNS(12.7% vs. 2.1%, P=0.004)와 viridans streptococci(11.0% vs. 3.1%, P=0.036)가 차지하는 비율이 더 높았다. 항생제 감수성 검사에서 그람양성균에서는 penicillin, oxacillin 및 vancomycin 내성률이 각각 83.3%, 48.5% 및 0.5%였으며, 그람음성균에서는 cefotaxime, piperacillin/tazobactam, imipenem, gentamicin 및 amikacin 내성률이 24.1%, 17.2%. 6.6%, 21.6% 및 14.2%이었다. 균혈증의 경과를 알 수 있었던 179례 중 42례(23.5%)가 중환자실 치료를 받았으며, 20례(11.2%)가 사망하였으며, 그람 음성균 감염의 경우 그람 양성균 감염에 비해 중환자실 치료율이 높았으며(26.5% vs. 10.3%, P=0.016), 중심 정맥관을 가진 경우에 중환자실 치료 빈도(34.4% vs. 10.8%, P<0.001)와 사망률(16.7 % vs. 4.8%, P=0.012)이 높았다. 결 론 : 최근 4년간 소아 종양 환자에서의 균혈증 분석 결과, 아직 그람음성균이 차지하는 빈도가 높으며 특히 호중구 감소증이 동반되었을 때 그람음성균에 대한 적절한 치료가 우선 시행되어야 하겠다. 하지만 그람양성균이 차지하는 비율이 증가하고 있는 것도 경험적 항생제 결정시 고려하여야 할 것으로 판단된다.

Keywords

Acknowledgement

Supported by : 서울대학교병원

References

  1. Gurney JG, Bondy ML. Epidemiology of childhood and adolescent cancer. In: Behrman RE, Kleigman RM, Jenson HB, editors. Nelson Textbook of Pediatrics. 17th ed. Philadelphia: WE Saunders Co 2004:1679-81
  2. Brown AE. Neutropenia, fever, and infection. Am J Med 1984;76:421-8 https://doi.org/10.1016/0002-9343(84)90661-2
  3. Brown AE. Management in the febrile, neutropenic patient with cancer: Therapeutic considerations. J Pediatr 1985;106:1035-41 https://doi.org/10.1016/S0022-3476(85)80265-1
  4. Pizzo PA. Management of fever in patients with cancer and treatment-Induced neutropenia. N Engl J Med 1993;328:1323-32 https://doi.org/10.1056/NEJM199305063281808
  5. Lee SL, Kim JS, Kim HS, Kang JM. A study on infection in childhood acute leukemia. Kor J Infect Dis 1990;22:33-41
  6. Watson RS, Carcillo JA, Linde-Zwirble WT, Clermont G, Lidicker J, Angus DC. The epidemiology of severe sepsis in children in the United States. Am J Respi Crit Care Med 2003;167:695-701 https://doi.org/10.1164/rccm.200207-682OC
  7. Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 2002;34:730-51 https://doi.org/10.1086/339215
  8. Pizzo PA. Rubin M. Freifeld A. Walsh TJ. The child with cancer and infection. I. Empiric therapy for fever and neutropenia and preventive strategies. J Pediatr 1991:119:679-94 https://doi.org/10.1016/S0022-3476(05)80281-1
  9. Weisman SJ, Scoopo FJ, Johnson GM, Altman AJ, Quinn JJ. Septicemia in pediatric oncology patients: The significance of viridans streptococcal infections. J Pediatr 1985;106:1035-41 https://doi.org/10.1016/S0022-3476(85)80265-1
  10. Celkan T, Ozkan A, Apak H, Diren S, Can G, Yuksel L, et al. Bacteremia in childhood cancer. J Trop Pediatr 2002;48:373-7 https://doi.org/10.1093/tropej/48.6.373
  11. Viscoli C, Castagnola E. Prophylaxis and empirical therapy for infection in cancer patients. In: Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas, and Bennetts principles and practice of infectious diseases. 6th ed. Philadelphia: Churchill Livingstone, 2006:3442-62
  12. Yun BY, Lee HJ. Septicemia in children with neoplastic disease. J Korean Pediatr Soc 1992;35:1481-91
  13. Choi EH, Pvo JW, Park JY, Kwon KB, Yun BY, Shin HY, et al. Infections in children with neoplastic disease. J Korean Pediatr Soc 1995;38:366-77
  14. Kim YH, Lee HD, Hah JO. Bacteremia in pediatric cancer patients: Causative organisms and antibiotic sensitivities. Korean J Pediatr 2005;48:619-23
  15. Mary JF, William AC, Michael ND, Geroge E, David WH, Janet FH, et al. Performance standards for antimicrobial susceptibility testing. Twelfth international supplement. P667, villanova, PA, National Committee for Clinical Laboratory Standards 2002
  16. Wade JC, Schimpff SC, Newman KA, Wiernik PH. Staphylococcus epidemidis: An increasing cause of infection in patients with granulocytopenia. Ann Intern Med 1982;97:503-8 https://doi.org/10.7326/0003-4819-97-4-503
  17. Rokusz L, Laszio L. Infections of febrile neutropenic patients in malignant hematological diseases(second study period). Mil Med 2005;170:653-7 https://doi.org/10.7205/MILMED.170.8.653
  18. Winston DJ, Dudnick DV, Chapin M, Ho WG, Gale RP, Martin WJ. Coagulase-negative staphylococcal bacteremia in patients receiving immunosuppressive therapy. Arch Intern Med 1983;143:32-6 https://doi.org/10.1001/archinte.143.1.32
  19. West DC, Marcin JP, Mawis R, He J, Nagle A, Dimand R. Children with cancer, fever, and treatment-induced neutropenia. Pediatr Emerg Care 2004;20:79-84 https://doi.org/10.1097/01.pec.0000113875.10140.40
  20. Ammann RA, Hirt A, Luthy AR, Aebi C. Predicting bacteremia in children with fever and chemotherapy-induced neutropenia. Pediatr Infect Dis J 2004;23:61-7 https://doi.org/10.1097/01.inf.0000106782.30100.4f
  21. Tamburro R. Pediatric cancer patients in clinical trials of sepsis: Factors that predispose to sepsis and stratify outcome. Pediatr Crit Care Med 2005;6(3 Suppl):87S-91S https://doi.org/10.1097/01.PCC.0000161288.00396.49
  22. Alexander SW, Wade KC, Hibberd PL, Parsons SK. Evaluation of risk prediction criteria for episodes of febrile neutropenia in children with cancer. J Pediatr Hematol Oncol 2002;24:38-42 https://doi.org/10.1097/00043426-200201000-00011
  23. Whimbey E, Kiehn TE, Brannon P, Blevins A, Armetrong D. Bacteremia and fungemia in patients with neoplastic disease. Am J Med 1987;82:723-30 https://doi.org/10.1016/0002-9343(87)90007-6
  24. Yoo JH, Choi SM, Lee DG, Choi JH, Shin WS, Min WS, et al. Prognositc factors influencing infection-related mortality in patients with acute leukemia in Korea. J Korean Med Sci 2005;20:31-5 https://doi.org/10.3346/jkms.2005.20.1.31
  25. Bodey GP, Buckley M, Sathe YS, Freireich EJ, Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med 1966;64:328-40 https://doi.org/10.7326/0003-4819-64-2-328
  26. Viscoli C. Management of infection in cancer patients: Studies of the EORTC International Antimicrobial Therapy Group(IATG). Eur J Cancer 2002;38(Suppl):82S-87S https://doi.org/10.1016/S0959-8049(01)00461-0
  27. Beekmann SE, Henderson DK. Infections caused by percutaneous intravascular devices. In: Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas, and Bennetts principles and practice of infectious diseases. 6th ed. Philadelphia: Churchill Livingstone, 2006:3442-62