簡易檢索 / 詳目顯示

研究生: 簡百秀
Jian, Bai-Xiu
論文名稱: 兒童菌血症、抗微生物藥物抗藥性與處方型態分析:前瞻性觀察之前驅研究
Bacteremia, Antimicrobial Resistance and Prescription Pattern in Pediatric Patients: Prospective Observational Pilot Study
指導教授: 鄭靜蘭
Cheng, Ching-Lan
共同指導教授: 林文亮
Lin, Wen-Liang
學位類別: 碩士
Master
系所名稱: 醫學院 - 臨床藥學與藥物科技研究所
Institute of Clinical Pharmacy and Pharmaceutical sciences
論文出版年: 2017
畢業學年度: 105
語文別: 中文
論文頁數: 103
中文關鍵詞: 抗微生物抗藥性小兒族群菌血症處方型態點盛行率調查
外文關鍵詞: antimicrobial resistance, pediatric bacteremia, prescribing pattern, point prevalence survey
相關次數: 點閱:127下載:3
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 背景
    抗微生物藥物是最常被處方予小兒族群的藥物,即使如此,關於微生物抗藥性的研究和用藥評估卻常常未納入小兒族群。過去研究已告訴我們抗微生物藥物的使用和抗藥性有關,但目前小兒族群的感染症致病菌相關的研究,仍僅限於特定的疾病族群或特殊的病房單位,例如血液腫瘤科或加護病房等。小兒族群的感染部位、感染來源和致病菌和成人族群不同,因此建立一套小兒族群的抗藥性監測系統是必要的。近年歐盟兒童抗生素抗藥性及處方計畫(Worldwide Antibiotic Resistance and Prescribing in European Children, ARPEC) 開始關注小兒族群的抗藥性問題,此計畫納入世界各地的醫院並分析抗藥性及處方型態,接著ARPEC計畫衍生至全球層級的GARPEC計畫。台灣尚未建立適用於小兒族群的監測作業流程。

    目的
    藉由參與GARPEC計畫,本研究目的有二:(1) 分析成大醫院小兒族群抗藥性菌血症的發生率及抗藥性情形;(2) 藉由點盛行率調查 (PPS) 評估成大醫院小兒族群抗微生物藥物處方型態。並且本研究為國內多中心研究的前驅研究。

    方法
    本研究以前瞻性病歷回顧的試驗設計進行,目的一的收案條件是2016年8月至2017年5月期間,血液培養出指定菌種、18歲以下的住院病患,並且依年齡分組分析病患的基本特性和抗藥性數據。目的二中每月一次PPS的調查期間為2016年1至12月,每個月隨機選出一天為調查日,納入調查日當天有使用抗微生物藥物或前一天有使用手術預防性抗生素的病人,依年齡或病房計算抗微生物藥物處方率,記錄抗微生物藥物處方的相關資訊,包含藥物、劑量、頻次、給藥途徑、適應症等,並且將這些處方依治療原因、感染部位、經驗性治療或確定治療 (definite/targeted therapy) 分類。研究中所有藥物依ATC level 3或4分類。以描述性統計呈現數據,包含次數、百分比、平均和中位數。本研究參與GARPEC計畫,符合該計畫期間的研究數據,去除個資後回報至GARPEC計畫。

    結果
    研究期間共有45位病人符合研究條件,包含49筆菌株報告,其中 31株 (63.3%) 對至少一種抗生素具有抗藥性。49株菌株中最常出現的是 Salmonella spp. (n=13),且有85%係從1歲以上菌血症兒童血液培養而得。抗藥性菌株中最常見的是E. coli (n=9),對ampicillin/sulbactam和cefazolin的敏感性分別僅有11%和22%。本研究發現7月齡以上的族群,造成菌血症的菌種已和成人族群相似。12次PPS納入的病房有1間小兒加護病房、1間新生兒加護病房和1間兒科普通病房,納入的573人次中有371 (65%) 人次使用至少一種抗微生物藥物,總計有645筆抗微生物處方,其中79.1%為治療性處方,20.9%為預防性處方。預防性處方中最常見的藥物類別是sulfonamides/trimethoprim (43%) 及antimycotics for systemic use (30%);而combinations of penicillins including beta-lactamase inhibitor則是治療性處方中最常被開立的藥物類別,最常見的治療適應症是下呼吸道感染 (22%)。

    結論
    本前驅研究發現小兒族群菌血症較過去的小兒族群及整體族群有較高的抗藥性,尤其是E. coli多對臨床上常用的抗生素具抗藥性。小兒族群抗微生物處方率較過去研究的整體族群高,暗示小兒族群較成人更容易被處方抗微生物藥物,因此未來應建立多中心的小兒族群抗微生物抗藥性及藥物使用的監測計畫。

    The antimicrobials are most common prescribed in children, but due to the lack of research in pediatric population, we know little about the resistance pattern and utilization of antimicrobials in this population. The existed literature about infections and pathogens in pediatric population often focus on specific situations or patients with specific diseases, such as oncological or community-acquired diseases. This study was aimed to estimate pediatric antimicrobial resistance, bloodstream infection rates and pathogens, and to describe the antimicrobial prescribing pattern by monthly point prevalence survey (PPS). We documented the positive blood cultures during August 2016 to May 2017 and the inclusion criteria were isolates reported studied pathogens, hospitalized patients aged less than 18 years old. Monthly PPS were conducted in 2016, selecting the survey days by simple random sampling. The participating wards were neonatal ICU (NICU), pediatric ICU (PICU) and general pediatric medical ward (GPMW). There were 49 isolates from 45 pediatric patients enrolled. Thirty-one (63%) of these 49 isolates were resistant pathogens. The resistance of E. coli to first-line empirical medications, like ampicillin/sulbactam and gentamicin, was serious than early study and general population. In the study of prescribing pattern, there were 573 person-times met the enrolled criteria, and 371 (65%) of them had been prescribed at least one antimicrobial. A total of 645 antimicrobial prescriptions were documented, in which the combinations of penicillins including beta-lactamase inhibitor were the most prescribed medications. Of all prescriptions, 79.1% were for therapeutic and 20.9% were for prophylactic use. The most common therapeutic indication was lower respiratory tract infections. In this pilot study, we establish a model that can be applied to multicenter studies in the future. Moreover, this study emphasized the need of antimicrobial resistance and utilization monitoring system for pediatric population.

    摘要 i Extended Abstract iii 誌謝 vi 目錄 vii 圖目錄 ix 表目錄 xi 縮寫對照表 xiii 第一篇、 兒童菌血症、抗生素抗藥性與處方型態分析 1 第一章、 研究背景 1 第二章、 文獻回顧 2 第一節、 抗生素抗藥性 2 第二節、 抗微生物藥物處方型態 11 第三章、 研究目的與重要性 17 第一節、 研究目的 17 第二節、 重要性 17 第四章、 研究方法 18 第一節、 研究設計 18 第二節、 定義 20 第三節、 研究流程 32 第四節、 統計方法 34 第五章、 研究結果 35 第一節、 研究族群納入與排除 35 第二節、 研究族群之基本資料 38 第三節、 抗藥性型態 45 第四節、 抗微生物藥物處方型態 49 第五節、 處方日劑量 57 第六章、 討論 59 第一節、 菌血症微生物學 59 第二節、 菌血症抗藥性與臨床衝擊 62 第三節、 抗微生物藥物處方率 66 第四節、 處方型態 71 第五節、 處方日劑量 79 第六節、 研究優勢與限制 81 第七章、 結論與建議 82 第八章、 未來研究方向 82 第二篇、 臨床藥事服務 83 第一章、 服務動機 83 第二章、 服務目的與方法 84 第一節、 目的 84 第二節、 方法 84 第三章、 結果 87 第四章、 感想與建議 92 參考文獻 93 附件一 97 附件二 98 附件三 99 附件四 100

    1. World Health Organization. Antimicrobial resistance. Fact sheet 2016 [cited 2017; Available from: http://www.who.int/mediacentre/factsheets/fs194/en/.
    2. Andrew F Shorr, Epidemiology and economic impact of meticillin-resistant Staphylococcus aureus. Pharmacoeconomics, 2007. 25(9): p. 751-768.
    3. Centers for Disease Control And Prevention, Antibiotic Resistance Threats in the United States, 2013. 2013. p. 114.
    4. M. E. A. De Kraker, et al., The changing epidemiology of bacteraemias in Europe: trends from the European Antimicrobial Resistance Surveillance System. Clinical Microbiology and Infection, 2013. 19(9): p. 860-868.
    5. Antje Neubert, Katja Taxis, and Ian C. K. Wong, Drug utilization in the paediatric population, in Drug Utilization Research. 2016, John Wiley & Sons, Ltd. p. 248-258.
    6. I. Levy, et al., A prospective study of Gram-negative bacteremia in children. Pediatr Infect Dis J, 1996. 15(2): p. 117-22.
    7. H. P. Lai, et al., Bacteremia in hematological and oncological children with febrile neutropenia: experience in a tertiary medical center in Taiwan. J Microbiol Immunol Infect, 2003. 36(3): p. 197-202.
    8. N. C. Lee, et al., Neonatal bacteremia in a neonatal intensive care unit: analysis of causative organisms and antimicrobial susceptibility. J Chin Med Assoc, 2004. 67(1): p. 15-20.
    9. Ming-Jenn Lee, et al., Clinical Features of Pediatric Pneumococcal Bacteremia in Mid-Taiwan: A Single-Institute Experience. Journal of Pediatric Respiratory Disease, 2012. 8(3): p. 85-91.
    10. H. L. Chen, et al., Clinical analysis of Enterobacter bacteremia in pediatric patients: a 10-year study. J Microbiol Immunol Infect, 2014. 47(5): p. 381-6.
    11. Y. T. Ting, et al., Epidemiology of community-acquired bacteremia among infants in a medical center in Taiwan, 2002-2011. J Microbiol Immunol Infect, 2015. 48(4): p. 413-8.
    12. Jose M. Munita and Cesar A. Arias, Mechanisms of Antibiotic Resistance. Microbiol Spectr, 2016. 4(2): p. VMBF-0016-2015.
    13. P. M. Bennett, Plasmid encoded antibiotic resistance: acquisition and transfer of antibiotic resistance genes in bacteria. Br J Pharmacol, 2008. 153(Suppl 1): p. S347-57.
    14. 盧柏樑, 新的超級細菌在台灣-具碳青黴烯抗藥性之腸桿菌科細菌. 內科學誌, 2015. 26(6): p. 328-335.
    15. 王任賢 and 張金堅, 台灣細菌抗藥性偏高之原因與解決方案. 臺灣醫界, 2015. 58(7): p. 9-11.
    16. S. Vasoo, J. N. Barreto, and P. K. Tosh, Emerging issues in gram-negative bacterial resistance: an update for the practicing clinician. Mayo Clin Proc, 2015. 90(3): p. 395-403.
    17. European Centre for Disease Prevention And Control, Antimicrobial resistance surveillance in Europe 2015. Annual Report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). 2017, ECDC: Stockholm.
    18. P. R. Lagace-Wiens, et al., Trends in antibiotic resistance over time among pathogens from Canadian hospitals: results of the CANWARD study 2007-11. J Antimicrob Chemother, 2013. 68 Suppl 1: p. i23-9.
    19. Economics & Policy Center for Disease Dynamics. ResistanceMap. [cited 2017 May 18]; Available from: https://resistancemap.cddep.org/index.php.
    20. 衛生福利部疾病管制署. 抗微生物製劑相關管制措施. [cited 2017 May 17]; Available from: http://www.cdc.gov.tw/professional/list.aspx?treeid=beac9c103df952c4&nowtreeid=85E6E6FF241BB9F6.
    21. Centers for Disease Control And Prevention. Antibiotic Resistance: Urgent Health Threat Jeopardizing Modern Medicine. 2015 [cited 2017 May 17]; Available from: https://blogs.cdc.gov/safehealthcare/antibiotic-resistance-health-threat-jeopardizing-modern-medicine/.
    22. R. R. Roberts, et al., Hospital and societal costs of antimicrobial-resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship. Clin Infect Dis, 2009. 49(8): p. 1175-84.
    23. 林明鋒, 從細菌的抗藥性談抗生素管理的重要性. 感染控制雜誌, 2012. 22(3): p. 115-123.
    24. European Medicines Agency. Antimicrobial resistance. [cited 2017 May 17]; Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/general/general_content_000439.jsp.
    25. N. Y. Lee, et al., Clinical and economic impact of multidrug resistance in nosocomial Acinetobacter baumannii bacteremia. Infect Control Hosp Epidemiol, 2007. 28(6): p. 713-9.
    26. 周偉惠, 曾淑慧, and 柯玉芬, 台灣抗生素抗藥性管理政策與國家型抗生素管理計畫. 感染控制雜誌, 2015. 25(3): p. 133-139.
    27. World Economic Forum, Global Risks 2013 Eighth Edition. 2013.
    28. E. Leung, et al., The WHO policy package to combat antimicrobial resistance. Bull World Health Organ, 2011. 89(5): p. 390-2.
    29. S Vergnano, et al., Antimicrobial resistance, prescribing and efficacy in children from the European to the global scene: From ARPEC to GARPEC. Journal of Pediatric Infectious Diseases, 2014. 9(3): p. 135-137.
    30. Nikos Spyridis and Mike Sharland, The European Union Antibiotic Awareness Day: the paediatric perspective. Archives of Disease in Childhood, 2008. 93(11): p. 909-910.
    31. B. Amadeo, et al., European Surveillance of Antibiotic Consumption (ESAC) point prevalence survey 2008: paediatric antimicrobial prescribing in 32 hospitals of 21 European countries. J Antimicrob Chemother, 2010. 65(10): p. 2247-52.
    32. A. Versporten, et al., The antibiotic resistance and prescribing in European Children project: a neonatal and pediatric antimicrobial web-based point prevalence survey in 73 hospitals worldwide. Pediatr Infect Dis J, 2013. 32(6): p. e242-53.
    33. A. Versporten, et al., The Worldwide Antibiotic Resistance and Prescribing in European Children (ARPEC) point prevalence survey: developing hospital-quality indicators of antibiotic prescribing for children. J Antimicrob Chemother, 2016. 71(4): p. 1106-17.
    34. Paul A. Harris, et al., Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support. Journal of Biomedical Informatics, 2009. 42(2): p. 377-381.
    35. 李金翰, 小兒西醫門診抗生素處方型態及用藥品質分析. 成功大學臨床藥學與藥物科技研究所學位論文, 2012: p. 1-135.
    36. 施智源, et al., 台灣急性照護醫院的醫療照護相關感染與抗微生物藥物使用點盛行率調查之先驅研究. 感染控制雜誌, 2015. 25(4): p. 153-167.
    37. Clinical & Laboratory Standards Institute, Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Fourth Informational Supplement. 2012: Wayne, PA: Clinical and Laboratory Standards Institute.
    38. 林委正, 高雅慧, and 柯文謙, 血液培養污染之臨床衝擊及改善方法. 感染控制雜誌, 2004. 14(6): p. 390-397.
    39. S. Ireland, S. Larkins, and Y. Kandasamy, Group B streptococcal infection in the first 90 days of life in North Queensland. Aust N Z J Obstet Gynaecol, 2014. 54(2): p. 146-51.
    40. J. H. Wu, et al., Neonatal sepsis: a 6-year analysis in a neonatal care unit in Taiwan. Pediatr Neonatol, 2009. 50(3): p. 88-95.
    41. M. J. Bizzarro, et al., Seventy-five years of neonatal sepsis at Yale: 1928-2003. Pediatrics, 2005. 116(3): p. 595-602.
    42. J. R. Verani, L. Mcgee, and S. J. Schrag, Prevention of perinatal group B streptococcal disease--revised guidelines from CDC, 2010. MMWR Recomm Rep, 2010. 59(Rr-10): p. 1-36.
    43. T. T. Ao, et al., Global burden of invasive nontyphoidal Salmonella disease, 2010(1). Emerg Infect Dis, 2015. 21(6).
    44. C. H. Kao, et al., Isolated pathogens and clinical outcomes of adult bacteremia in the emergency department: a retrospective study in a tertiary Referral Center. J Microbiol Immunol Infect, 2011. 44(3): p. 215-21.
    45. 衛生福利部疾病管制署, 台灣流感速訊2014~2016年.
    46. 衛生福利部疾病管制署. 傳染病統計資料查詢系統 [cited 2017; Available from: https://nidss.cdc.gov.tw/ch/.
    47. W. P. Witt, A. J. Weiss, and A. Elixhauser, Overview of Hospital Stays for Children in the United States, 2012, in Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. 2014, Agency for Healthcare Research and Quality (US): Rockville (MD).
    48. S. Leekha, C. L. Terrell, and R. S. Edson, General Principles of Antimicrobial Therapy. Mayo Clin Proc, 2011. 86(2): p. 156-67.
    49. D. Berild, et al., Adjustment of antibiotic treatment according to the results of blood cultures leads to decreased antibiotic use and costs. J Antimicrob Chemother, 2006. 57(2): p. 326-30.
    50. 衛生福利部疾病管制署, ASP抗生素管理手冊. 防疫學苑系列. 2015.
    51. Herman Goossens, Results on the 2015 Global-PPS, in ECCMID. 2016: Amsterdam, The Netherlands.
    52. P. B. Smith and D. K. Benjamin, Choosing the right empirical antibiotics for neonates. Arch Dis Child Fetal Neonatal Ed, 2011. 96(1): p. F2-3.
    53. 葉盈池, 劉人瑋, and 王春玉, Fluoroquinolone 用於小兒之安全性. 藥學雜誌, 2013. 29(1): p. 56-60.
    54. 台灣兒科醫學會. 兒童氟喹諾酮抗生素使用建議. 2012 [cited 2017; Available from: http://www.pediatr.org.tw/member/bedside_info.asp?id=14.
    55. 施議強, 許清曉, and 侯承伯, Fluoroquinolone類抗生素新觀與分類. 臺灣醫界, 2001. 44(12).
    56. Fda. Drugs@FDA: FDA Approved Drug Products: Ciprofloxacin 2004/3/25. 2017 [cited 2017 August 7]; Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=019537.
    57. 孫銘聰, 蘇迎士, and 彭銘業, 藥物耗用標準化之定義每日劑量(defined daily dose)介紹及應用. 感染控制雜誌, 2008. 18(1): p. 41-46.
    58. Association American Pharmacists and Inc Lexi-Comp, Drug information handbook : a clinically relevant resource for all healthcare professionals. 25th edition. ed. Lexicomp drug reference handbooks. 2016, Hudson, Ohio: Lexicomp. 2,035 pages.
    59. T. B. Y. Liem, et al., Quantifying antibiotic use in paediatrics: a proposal for neonatal DDDs. Eur J Clin Microbiol Infect Dis, 2010. 29(10): p. 1301-3.

    下載圖示 校內:2022-07-31公開
    校外:2022-07-31公開
    QR CODE