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3 讨论                                                     Executive  summary:clinical  practice  guideline  for  the
              罹患血液系统恶性肿瘤的高风险患者中,如接受诱                               management of candidiasis:2016 update by the Infectious
          导化疗的急性白血病患者、造血干细胞移植患者,常见                                 Diseases Society of America[J]. Clin Infect Dis,2016,62
          IFI。随着中性粒细胞减少的持续时间和严重程度增加、                              (4):409-417.
                                                              [ 5 ]  LEWIS R E,WIEDERHOLD N P. The solubility ceiling:
          使用抗菌药物的时间延长及化疗周期增加,IFI 会导致
                              [1]
          病情加重和病死率增加 。                                             a  rationale  for  continuous  infusion  amphotericin  B
                                                                   therapy?[J]. Clin Infect Dis,2003,37(6):871-872.
              两性霉素B是一种多烯类抗真菌药,对多种致病真                          [ 6 ]  GREEN  S,HIGGINS  J  P.  Preparing  a  cochrane  review
                        [4]
          菌具有体外活性 。两性霉素B通过破坏真菌细胞壁合
                                                                   [M]//Cochrane Handbook for Systematic Reviews of Inter‐
          成而发挥抗真菌作用,能与甾醇类(主要是麦角固醇)结                                ventions. Chichester,UK:John Wiley & Sons,Ltd,2008:
          合,在细胞壁上形成孔道,进而导致细胞内容物外漏 。                                11-30.
                                                        [4]
          这种亲和力也解释了该药对某些哺乳动物细胞的有毒                             [ 7 ]  STANG  A.  Critical  evaluation  of  the  Newcastle-Ottawa
            [4]
          性 ,因此两性霉素 B 的毒副作用相对较多。尽管已经                               scale for the assessment of the quality of nonrandomized
          引入多种新型抗真菌药物用于全身性真菌感染的治疗,                                 studies  in  meta-analyses[J].  Eur  J  Epidemiol,2010,25
          但是两性霉素 B 仍然是多种严重的 IFI 的标准治疗药                            (9):603-605.
          物 [2―3] 。然而,静脉使用两性霉素B引起的毒性限制了其                      [ 8 ]  ERIKSSON U,SEIFERT B,SCHAFFNER A. Comparison
                  [4]
          广泛使用 。通过药动学/药效学优化改变输注方式在                                 of effects of amphotericin B deoxycholate infused over 4
          美罗培南或者哌拉西林他唑巴坦钠治疗革兰氏阴性菌                                  or  24  hours:randomised  controlled  trial[J].  BMJ,2001,
                                     [15]
          所致脓毒症中已经获得了认可 ,24 h 持续泵入两性霉                              322(7286):579-582.
                                                              [ 9 ]  LEE Y K,KIM Y H,JEONG O H M D. Comparison of
          素B是否较间断滴注能提高疗效、降低不良反应?为此
                                                                   effects  and  side  effects  of  amphotericin  B  deoxycholate
          本研究采用 Meta 分析的方法对两性霉素 B 两种不同输                            infusion over 6 versus 24 hours in children with cancer[J].
          注方式的疗效和安全性进行系统评价,旨在为合理使用
                                                                   Korean J Pediatr Hematol Oncol,2003,10(2):223-229.
          两性霉素 B 治疗 IFI 提供依据。本研究结果显示,试验                       [10]  PELEG A Y,WOODS M L. Continuous and 4 h infusion
          组患者的临床有效率显著优于对照组,全因死亡率、输                                 of  amphotericin  B:a  comparative  study  involving  high-
          液反应发生率均显著低于对照组,但两组患者的肾损害                                 risk  haematology  patients[J].  J  Antimicrob  Chemother,
          发生率比较无显著差异。                                              2004,54(4):803-808.
              本研究尚存在一定的局限性:(1)纳入 RCT 仅有 1                     [11]  SCHULENBURG  A,SPERR  W,RABITSCH  W,et  al.
          篇,其余6篇均为队列研究,由于两种研究之间在试验设                                Brief  report:practicability  and  safety  of  amphotericin  B
          计、干预及质量控制上存在很大的差异,将两种研究均                                 deoxycholate  as  continuous  infusion  in  neutropenic  pa‐
          纳入Meta分析可能使得结果可信度降低;(2)多数研究                              tients  with  hematological  malignancies[J].  Leuk  Lym‐
          并未提及疗程,不能排除试验组与对照组患者两性霉素                                 phoma,2005,46(8):1163-1167.
                                                              [12]  MAHAROM P,THAMLIKITKUL V. Implementation of
          B使用时间存在差异,这可能会引起结果偏倚;(3)部分
                                                                   clinical  practice  policy  on  the  continuous  intravenous
          研究纳入的患者数较少,需要更多的研究进一步评价;
                                                                   administration  of  amphotericin  B  deoxycholate[J].  Chot‐
         (4)各项结局指标纳入的研究数均小于 10,未进行发表                               maihet Thangphaet,2006,89(Suppl 5):S118-S124.
          偏倚分析。故本研究所得结论尚需更多高质量 RCT 进
                                                              [13]  ALTMANNSBERGER P,HOLLER E,ANDREESEN R,
          一步验证。                                                    et al. Amphotericin B deoxycholate:no significant advan‐
          参考文献                                                     tage of a 24 h over a 6 h infusion schedule[J]. J Antimi‐
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               children  with  cancer  and/or  undergoing  hematopoietic   Nephrotoxicity of continuous amphotericin B in critically
               stem-cell transplantation[J]. J Clin Oncol,2012,30(35):  ill patients with abdominal sepsis:a retrospective analysis
               4427-4438.                                          with  propensity  score  matching[J].  J  Antimicrob  Che‐
          [ 2 ]  BRANCH R A. Prevention of amphotericin B-induced renal   mother,2021,77(1):246-252.
               impairment. A review on the use of sodium supplementation  [15]  FALAGAS M E,TANSARLI G S,IKAWA K,et al. Clini‐
               [J]. Arch Intern Med,1988,148(11):2389-2394.        cal  outcomes  with  extended  or  continuous  versus  short-
          [ 3 ]  PATTERSON T F,THOMPSON G R 3rd,DENNING D          term intravenous infusion of carbapenems and piperacillin/
               W,et al. Practice guidelines for the diagnosis and manage‐  tazobactam:a  systematic  review  and  meta-analysis[J].
               ment  of  aspergillosis:2016  update  by  the  Infectious         Clin Infect Dis,2013,56(2):272-282.
               Diseases Society of America[J]. Clin Infect Dis,2016,63      (收稿日期:2023-01-19  修回日期:2023-02-10)
              (4):e1-e60.                                                                         (编辑:舒安琴)
          [ 4 ]  PAPPAS  P  G,KAUFFMAN  C  A,ANDES  D  R,et  al.



          · 1118 ·    China Pharmacy  2023 Vol. 34  No. 9                              中国药房  2023年第34卷第9期
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