piperacillin-tazobactam, 투여 방법, infusion, IV push

목적

Piperacillin/tazobactam is a broad-spectrum antibiotic that is widely used and commonly administered via the intravenous (i.v.) piggyback route over 0.5 to 4.0 hours. Recommendations for i.v. push (IVP) administration of piperacillin/tazobactam are lacking due to the high osmolality of the solution. The primary objective of this study was to retrospectively assess the safety and tolerability of piperacillin/tazobactam administered peripherally by IVP.

 

많은 베타락탐계 항생제가 비교적 안전하게 IVP가 가능하다.

1. Butterfield-Cowper J, Burgner K. Effects of i.v. push administration on β-lactam pharmacodynamics. Am J Health–Syst Pharm. 2017;74(9):e170-e175.
2. Garrelts J, Ast D, LaRocca J, Smith D, Peterie J. Postinfusion phlebitis after intravenous push versus intravenous piggyback administration of antimicrobial agents. Clin Pharm. 1988;7(10):760-765. 
3. Nowobilski-Vasilios A, Poole S. Development and preliminary outcomes of a program for administering antimicrobials by i.v. push in home care. Am J Health-Syst Pharm. 1999;56(1):76-79.
4. Spencer S, Ipema H, Hartke P, et al. Intravenous push administration of antibiotics: literature and considerations. Hosp Pharm. 2018;53(3):157-169.
5. Wiskirchen D, Housman S, Quintiliani R, Nicolau D, Kuti J. Comparative pharmacokinetics, pharmacodynamics, and tolerability of ertapenem 1 gram/day administered as a rapid 5-minute infusion versus the standard 30-minute infusion in healthy adult volunteers. Pharmacotherapy. 2013;33(3):266-274.

 

방법

A retrospective chart review was conducted to evaluate adverse drug reactions after administration of a single dose of IVP piperacillin/ tazobactam through a peripheral line in an emergency department from August 2016 through November 2017.

 

결과

A total of 1,813 patients received 1 dose of IVP piperacillin/ tazobactam during the study timeframe. Three hundred patients were randomly selected for assessment of safety and tolerability. Two hundred ninety-nine patients (99.7%) tolerated IVP piperacillin/tazobactam. One patient had an allergic reaction that included itching and hives. No infusion-related reactions were documented.

 

결론

IVP administration of piperacillin/tazobactam through a peripheral site is safe and tolerable for adult patients.

 

 

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(1) 삼투압

Peripheral administration of solutions with osmolality greater than 900 mOsm/kg is discouraged due to the risk of infusion-related reactions such as discomfort, phlebitis, and extravasation. 👉 일반적으로 삼투압이 900 mOsm/kg 이상인 약제를 말초혈관으로 주입 시 정맥염이나 불편감 등을 유발하므로 권장하지 않는다.

위의 내용은 2014 ASPEN(2014 American Society for Parenteral and Enteral Nutrition clinical guidelines)의 가이드라인에서 parenteral nutrition 제제에 대한 weak level로 권장되는 내용이다. 이를 근거로 외삽되어 모든 약제에 대해 적용되었다.  하지만 고삼투 약제(3% sodium chloride (1,027 mOsm/kg), 20% and 25% mannitol (1,098 and 1,372 mOsm/kg, respectively), and 8.4% sodium bicarbonate (2,000 mOsm/kg))는 합병증 없이 말초 혈관으로 자주 안전하게 IVP로 투여된다.

📌 응급실에서 3% 염화나트륨액(HTS; hypertonic saline)과 만니톨의 말초혈관으로의 투여의 안정성에 대해 후향적으로 평가함.

This study included adult and pediatric patients given either 3% HTS or mannitol 20% or 25% via PIV while in the ED at LLUMC between April 1, 2013 and September 30, 2015.

 In the ED at LLUMC, bolus PIV administration of 3% HTS and mannitol is permitted during medical emergencies for adult and pediatric patients. HTS is usually administered as a 5 mL/kg bolus, while mannitol is administered as a 1 g/kg bolus. Bolus doses can be repeated at the discretion of the treating health care professional. Health care professionals can also order HTS or mannitol as continuous infusions, although bolus dosing is preferred due to more rapid administration

 

 

There were no incidences of extravasation among patients given 3% HTS or mannitol. Clinicians should reconsider recommendations to restrict HTS or mannitol to central lines.

 

 

continuous infusion 방법이 포함되긴 하였지만 수가 적기 때문에 prolonfed administration strategy에 대한 추가적인 안정성 평가 연구가 필요하다.

 

 

 

piperacillin/tazobactam의 삼투압

성분명	용량	희석액	희석 부피	삼투압(mOsm/kg)
piperacillin-tazobactam	3.375-g	NS	10 mL	1,278
piperacillin-tazobactam	4.5-g	NS	20 mL	930

 

 

(2) Pharmacokinetic parameter

piperacillin/tazobactam은 대표적인 시간 의존적 항생제이다. 즉 병원체의 MIC 이상의 혈장 농도를 오래 유지할수록 효과적인 약물이다. IV push로 투입 시 30분-4시간동안 투여했을 때만큼의 효과를 가질 수 있는지에 대해 의문이다. 따라서 이번 연구에서 도입하였던 방법도 응급실에서 첫 투여만 IVP로 투여하고 그 이후(2번째 투여부터) prolonded infusion(4시간) 방법으로 투여하였다.

 

(3) IVP의 장점

First-dose IVP antibiotics in the ED have been shown to decrease time to initial antibiotic administration and decrease cost due to the lack of a need for supplies and nursing time required for traditional i.v. infusion. 👉 의료부담 절감

 

 

 

reference:

1) Hays, William Blake, and Tara Flack. "Safety and tolerability of iv push piperacillin/tazobactam within an emergency department." American Journal of Health-System Pharmacy 77.13 (2020): 1051-1053.

2) Mesghali E, Fitter S, Bahjri K, Moussavi K. Safety of peripheral line administration of 3% hypertonic saline and mannitol in the emergency department. J Emerg Med. 2019;56(4):431-436