さまよう薬剤師のブログ

学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense ID pharmacist.

βラクタム系抗菌薬の長時間投与

長時間投与や持続投与が有用であれば…と思う瞬間は多いです。
 
PK/PD的に有用そうですが、臨床的アウトカムが少ないと言われていました。
少しずつ、エビデンスが増えていますが、どうでしょう。
 
持続投与は、IEや肺炎球菌肺炎治療を参考にした、PCG 12 or 24時間投与 以外は.......という施設が多いのではないでしょうか?
 
余談ですが、
今、私の子が入院しています。
抗菌薬ではありませんが、数時間おきの点滴があり、点滴変更時に、泣いたり不安な顔するので、長時間投与や持続投与が可能であれば、良いケースもあるな〜と、治療効果以外の患者視点でも思います。
 
そこで、注目度が増している!?
 
βラクタム系抗菌薬の長時間投与を復習
 
UpToDate より引用
 

Beta-lactam antibiotics demonstrate a time-dependent effect on bacterial eradication. Infusing the antibiotic over a prolonged period of time (eg, over four hours at each dose or even continuously) can more effectively attain pharmacodynamic target levels compared with short, intermittent infusions. This pharmacologic advantage offers a potential clinical benefit to patients with altered pharmacokinetics or with infections due to less susceptible pathogens.

 
Clinical data suggest that prolonged infusions of beta-lactams are at least equally effective as traditional intermittent infusions for gram-negative infections. Observational studies suggest that prolonged infusions of piperacillin-tazobactam in critically ill patients is associated with a mortality benefit compared with intermittent infusions.
 
Additional potential benefits of prolonged infusion strategies include cost savings, ease of administration in ambulatory settings, and a theoretical reduction in risk of acquired drug resistance. 
 
Potential drawbacks to prolonged infusion beta-lactam dosing strategies include several logistical barriers, such as need for intravenous line access, drug stability at room temperature, and compatibility with coadministered intravenous drugs. 
 
Indications for the use of prolonged infusion strategies with beta-lactams are not established. The pharmacologic and clinical data indicate that patients who have an elevated risk of drug-resistant pathogens or who are critically ill in the setting of a severe infection are most likely to benefit. When piperacillin-tazobactam, meropenem, imipenem, or cefepime is chosen for treatment in such patients, we suggest a prolonged infusion dosing strategy (Grade 2C). In particular, we favor prolonged infusion dosing for critically ill patients with gram-negative rod infections and for patients with infections due to gram-negative rods that have elevated but susceptible minimum inhibitory concentrations (MIC) to the chosen agent. The decision to use this dosing strategy should also take into account logistical issues such as staffing or intravenous access availability.
 
We suggest not using a prolonged infusion strategy with doripenem because of limited data demonstrating potential safety concerns (Grade 2C).
 
Optimal dosing for prolonged infusion of beta-lactams has not been established. Our preferred dosing for adult patients with adequate intravenous access is based on data from pharmacodynamic models. Beta-lactams are dose adjusted for renal impairment.
 
f:id:akinohanayuki:20160223114304j:image
f:id:akinohanayuki:20160223114312j:image
f:id:akinohanayuki:20160223114338j:image
 
おすすめ文献
 
Clin Infect Dis. 2007;44(3):357.
Antimicrob Agents Chemother. 2009 May;53(5):2014-9. Epub 2009 Mar 2.
Pharmacotherapy. 2011 Aug;31(8):767-75.
Clin Infect Dis. 2013 Jan;56(2):272-82. Epub 2012 Dec 14.
f:id:akinohanayuki:20160223115642j:image
f:id:akinohanayuki:20160223115906j:image
f:id:akinohanayuki:20160223115912j:image
 
Antimicrob Agents Chemother. 2013 Jul;57(7):2907-12. Epub 2013 Apr 9.
Ann Pharmacother. 2013;47(2):170.
Clin Infect Dis. 2013 Jan;56(2):236-44. Epub 2012 Dec 14.
  • Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicenter double-blind, randomized controlled trial.
  • PMID 23074313
  • free
  • http://www.ncbi.nlm.nih.gov/pubmed/?term=23074313

  • P) severe sepsis : Sixty patients
  • E) continuous infusion
  • C) intermittent bolus dosing
  • O) Clinical cure (70% vs 43%; P = .037)
  •      ICU-free days (19.5 vs 17 days; P = .14)
Cochrane Database Syst Rev. 2013;3:CD008481.
Clin. Infect. Dis. 2014 Apr; 58(8):1072-83.
Int J Antimicrob Agents. 2014 Feb;43(2):105-13. Epub 2013 Nov 24.
  • Prolonging β-lactam infusion: a review of the rationale and evidence, and guidance for implementation.
  • PMID 24359838
J Antimicrob Chemother. 2014 Sep;69(9):2556-62. Epub 2014 May 22.
Int J Antimicrob Agents. 2014 May;43(5):403-11. Epub 2014 Mar 1.
f:id:akinohanayuki:20160223120718j:image
f:id:akinohanayuki:20160223120729j:image
 
Antimicrob. Agents Chemother. 2015 Apr; 59(4):1905-9.
Am. J. Respir. Crit. Care Med. 2015 Dec 1; 192(11):1298-305.
  • A Multicenter Randomized Trial of Continuous versus Intermittent β-Lactam Infusion in Severe Sepsis.
  • PMID 26200166
  • http://www.ncbi.nlm.nih.gov/pubmed/?term=26200166

  • P) severe sepsis 432patients
  • E) antibiotic via continuous
  • C) 30-minute intermittent infusion 
  • O) ICU-free days: 18 days and 20 days in the continuous and intermittent groups          (P = 0.38).
  •      90-day survival: 74.3% (156 of 210) and 72.5% (158 of 218); hazard ratio, 0.91        (95% confidence interval, 0.63-1.31; P = 0.61).
  •      Clinical cure : 52.4% (111 of 212) and 49.5% (109 of 220); odds ratio, 1.12              (95% confidence interval, 0.77-1.63; P = 0.56). 
Intensive Care Med 2016 Jan 11
  • Beta-Lactam Infusion in Severe Sepsis (BLISS): a prospective, two-centre, open-labelled randomised controlled trial of continuous versus intermittent beta-lactam infusion in critically ill patients with severe sepsis
  • PMID 26754759
  • http://www.ncbi.nlm.nih.gov/pubmed/?term=26754759

  • P) severe sepsis who were not on renal replacement therapy (RRT) : 140 patients
  • E) CI
  • C) IB dosing
  • O) clinical cure rates (56 versus 34 %, p = 0.011)
  •      higher median ventilator-free days (22 versus 14 days, p < 0.043) 
J. Antimicrob. Chemother. 2016 Jan; 71(1):196-207.
  • Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort.
  • PMID 26433783
  • http://www.ncbi.nlm.nih.gov/pubmed/?term=26433783