Extended infusion versus intermittent infusion of Piperacillin/ tazobactam: altering current methods to optimize future outcome
Main Article Content
Keywords
Piperacillin, Tazobactam, Infusion, Antibiotics
Abstract
Due to worldwide bacterial resistance, researchers and clinicians were required to optimize existing antimicrobials by influencing the pharmacokinetics and pharmacodynamics (PK/PD) features. Piperacillin/tazobactam (PIP/TZB) is one of the most frequently empirical antibiotics prescribed globally. The aim of the review was to evaluate the use of an extended infusion (EI) versus an intermittent infusion (II) of PIP/TZB in hospital settings in terms of patient safety and efficacy. Several PK/PD studies assessed the use of an extended infusion of PIP/TZB to reach different minimum inhibitory concentration (MIC) levels for many microorganisms including Pseudomonas aeruginosa. One of the main parameters to define the size of the effect of PIP/TZB to various microorganisms is the percentage of time the free drug concentration above MIC (%fT > MIC). Many studies have compared extended infusion (EI) versus intermittent infusion (II) in terms of mortality rate, clinical cure or efficacy, length of stay whether in an intensive care unit (ICU) or hospital, duration of therapy, and cost. The clinical data reviewed in this article include PK/PD studies, prospective trials, systematic reviews, and meta-analysis. The review emphasized the role of an extended infusion in a population with altered pharmacokinetics including patients on continuous renal replacement therapy (CRRT), critically ill patients with augmented renal clearance, and patients with cystic fibrosis. Our review reports a positive trend when using an extended infusion of PIP/TZB which encourages the adoption and implementation of the extended infusion to achieve positive patient outcomes. Nevertheless, more studies are required to attain generalizable and reliable data to determine whether an extended infusion improves patient outcomes.
References
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5. Osthoff M, Siegemund M, Balestra G, et al. Prolonged administration of β-lactam antibiotics - a comprehensive review and
critical appraisal. Swiss Med Wkly. 2016;146(1):w14368. https://doi.org/10.4414/smw.2016.14368
6. Kaufman SE, Donnell RW, Hickey WS. Rationale and evidence for extended infusion of piperacillin-tazobactam. Am J Health
Syst Pharm. 2011;68(16):1521-1526. https://doi.org/10.2146/ajhp100694
7. Rizk NA, Kanafani ZA, Tabaja HZ, et al. Extended infusion of beta-lactam antibiotics: optimizing therapy in critically-ill patients
in the era of antimicrobial resistance. Expert Rev Anti Infect Ther. 2017;15(7):645-652. https://doi.org/10.1080/14787210.20
17.1348894
8. Gin A, Dilay L, Karlowsky JA, et al. Piperacillin-tazobactam: a beta-lactam/beta-lactamase inhibitor combination. Expert Rev
Anti Infect Ther. 2007;5(3):365-383. https://doi.org/10.1586/14787210.5.3.365
9. Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases
Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016;62(10):e51-77. https://doi.
org/10.1097/ipc.0b013e318068b1c0
10. Dellit TH, Owens RC, McGowan JE, et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology
of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis.
2007;44(2):159-177. https://doi.org/10.1086/510393
11. Winstead EM, Ratliff PD, Hickson RP, et al. Evaluation of an alternative extended-infusion piperacillin-tazobactam dosing
strategy for the treatment of gram-negative infections. Int J Clin Pharm. 2016;38(5):1087-1093. https://doi.org/10.1007/
s11096-016-0334-1
12. Dow R, Rose W, Fox B, et al. Retrospective Study of Prolonged Versus Intermittent Infusion Piperacillin-Tazobactam
and Meropenem in Intensive Care Unit Patients at an Academic Medical Center. Infectious Diseases in Clinical Practice.
2011;19(1):413-417. https://doi.org/10.1097/ipc.0b013e31822e9bf5
13. Lodise TP, Lomaestro B, Drusano GL. Piperacillin-tazobactam for Pseudomonas aeruginosa infection: clinical implications of an
extended-infusion dosing strategy. Clin Infect Dis. 2007;44(3):357-363. https://doi.org/10.3410/f.1088141.541136
14. Patel GW, Patel N, Lat A, et al. Outcomes of extended infusion piperacillin/tazobactam for documented Gram-negative
infections. Diagn Microbiol Infect Dis. 2009;64(2):236-240. https://doi.org/10.1016/j.diagmicrobio.2009.03.002
15. Bao H, Lv Y, Wang D, et al. Clinical outcomes of extended versus intermittent administration of piperacillin/tazobactam for the
treatment of hospital-acquired pneumonia: a randomized controlled trial. Eur J Clin Microbiol Infect Dis. 2017;36(3):459-466.
https://doi.org/10.1007/s10096-016-2819-1
16. Falagas ME, Tansarli GS, Ikawa K, et al. Clinical outcomes with extended or continuous versus short-term intravenous infusion
of carbapenems and piperacillin/tazobactam: a systematic review and meta-analysis. Clin Infect Dis. 2013;56(2):272-282.
https://doi.org/10.1093/cid/cis857
17. Rhodes NJ, Liu J, O’Donnell JN, et al. Prolonged Infusion Piperacillin-Tazobactam Decreases Mortality and Improves Outcomes
in Severely Ill Patients: Results of a Systematic Review and Meta-Analysis. Crit Care Med. 2018;46(2):236-243. https://doi.
org/10.1097/ccm.0000000000002836
18. Chan JD, Dellit TH, Lynch JB. Hospital Length of Stay Among Patients Receiving Intermittent Versus Prolonged
Piperacillin/Tazobactam Infusion in the Intensive Care Units. J Intensive Care Med. 2018;33(2):134-141. https://doi.
org/10.1177/0885066617708756
19. Lee GC, Liou H, Yee R, et al. Outcomes of extended-infusion piperacillin-tazobactam: a retrospective analysis of critically ill
patients. Clin Ther. 2012;34(12):2297-2300. https://doi.org/10.1016/j.clinthera.2012.11.005
20. Schmees PM, Bergman SJ, Strader BD, et al. Outcomes of an extended-infusion piperacillin-tazobactam protocol implementation
in a community teaching hospital adult intensive care unit. Am J Health Syst Pharm. 2016;73(11 Suppl 3):S100-105. https://
doi.org/10.2146/sp150041
21. Brunetti L, Poustchi S, Cunningham D, et al. Clinical and Economic Impact of Empirical Extended-Infusion Piperacillin-Tazobactam
in a Community Medical Center. Ann Pharmacother. 2015;49(7):754-760. https://doi.org/10.1177/1060028015579427
22. Cutro SR, Holzman R, Dubrovskaya Y, et al. Extended-Infusion versus standard-infusion piperacillin-tazobactam for sepsis
syndromes at a tertiary medical center. Antimicrob Agents Chemother. 2014;58(8):4470-4475. https://doi.org/10.1128/
aac.02759-14
23. McCormick H, Tomaka N, Baggett S, et al. Comparison of acute renal injury associated with intermittent and extended infusion
piperacillin/tazobactam. Am J Health Syst Pharm. 2015;72(11 Suppl 1):S25-30. https://doi.org/10.2146/sp150007
24. Levison ME, Levison JH. Pharmacokinetics and pharmacodynamics of antibacterial agents. Infect Dis Clin North Am.
2009;23(4):791-815. https://doi.org/10.1016/j.idc.2009.06.008
25. Hayashi Y, Roberts JA, Paterson DL, et al. Pharmacokinetic evaluation of piperacillin-tazobactam. Expert Opin Drug Metab
Toxicol. 2010;6(8):1017-1031. https://doi.org/10.1517/17425255.2010.506187
26. Turnidge JD. The pharmacodynamics of beta-lactams. Clin Infect Dis. 1998;27(1):10-22.
27. MacVane SH, Kuti JL, Nicolau DP. Prolonging β-lactam infusion: a review of the rationale and evidence, and guidance for
implementation. Int J Antimicrob Agents. 2014;43(2):105-113. https://doi.org/10.1016/j.ijantimicag.2013.10.021
28. CLSI. Performance Standards for Antimicrobial Disk Susceptibility Tests 2017.
29. Testing TECoAS. Breakpoint tables for interpretation of MICs and zone diameters 2020.
30. FDA U. Population Pharmacokinetics 2022; Available from: https://www.fda.gov/regulatory-information/search-fda-guidancedocuments/population-pharmacokinetics.
31. Roberts JA, Kirkpatrick CM, Lipman J. Monte Carlo simulations: maximizing antibiotic pharmacokinetic data to optimize clinical
practice for critically ill patients. J Antimicrob Chemother. 2011;66(2):227-231. https://doi.org/10.1093/jac/dkq449
32. Felton TW, Hope WW, Lomaestro BM, et al. Population pharmacokinetics of extended-infusion piperacillin-tazobactam
in hospitalized patients with nosocomial infections. Antimicrob Agents Chemother. 2012;56(8):4087-4094. https://doi.
org/10.1128/aac.00521-12
33. Patel N, Scheetz MH, Drusano GL, et al. Identification of optimal renal dosage adjustments for traditional and extendedinfusion piperacillin-tazobactam dosing regimens in hospitalized patients. Antimicrob Agents Chemother. 2010;54(1):460-465.
https://doi.org/10.1128/aac.00296-09
34. Shea KM, Cheatham SC, Smith DW, et al. Comparative pharmacodynamics of intermittent and prolonged infusions of
piperacillin/tazobactam using Monte Carlo simulations and steady-state pharmacokinetic data from hospitalized patients.
Ann Pharmacother. 2009;43(11):1747-1754. https://doi.org/10.1345/aph.1m462
35. De Waele J, Carlier M, Hoste E, et al. Extended versus bolus infusion of meropenem and piperacillin: a pharmacokinetic
analysis. Minerva Anestesiol. 2014;80(12):1302-1309.
36. Arnold HM, Hollands JM, Skrupky LP, et al. Prolonged infusion antibiotics for suspected gram-negative infections in the ICU: a
before-after study. Ann Pharmacother. 2013;47(2):170-180. https://doi.org/10.1345/aph.1r523
37. Fahimi F, Ghafari S, Jamaati H, et al. Continuous versus intermittent administration of piperacillin-tazobactam in intensive care
unit patients with ventilator-associated pneumonia. Indian J Crit Care Med. 2012;16(3):141-147. https://doi.org/10.4103/0972-
5229.102083
38. Fan SY, Shum HP, Cheng WY, et al. Clinical Outcomes of Extended Versus Intermittent Infusion of Piperacillin/Tazobactam in
Critically Ill Patients: A Prospective Clinical Trial. Pharmacotherapy. 2017;37(1):109-119. https://doi.org/10.1002/phar.1875
39. Lyu Y, Yang Y, Li X, et al. Selection of piperacillin/tazobactam infusion mode guided by SOFA score in cancer patients with
hospital-acquired pneumonia: a randomized controlled study. Ther Clin Risk Manag. 2018;14:31-37. https://doi.org/10.2147/
tcrm.s145681
40. Awissi DK, Beauchamp A, Hébert E, et al. Pharmacokinetics of an extended 4-hour infusion of piperacillin-tazobactam in
critically ill patients undergoing continuous renal replacement therapy. Pharmacotherapy. 2015;35(6):600-607. https://doi.
org/10.1002/phar.1604
41. Bugge JF. Pharmacokinetics and drug dosing adjustments during continuous venovenous hemofiltration or hemodiafiltration
in critically ill patients. Acta Anaesthesiol Scand. 2001;45(8):929-934. https://doi.org/10.1034/j.1399-6576.2001.450802.x
42. Shotwell MS, Nesbitt R, Madonia PN, et al. Pharmacokinetics and Pharmacodynamics of Extended Infusion Versus Short
Infusion Piperacillin-Tazobactam in Critically Ill Patients Undergoing CRRT. Clin J Am Soc Nephrol. 2016;11(8):1377-1383.
https://doi.org/10.2215/cjn.10260915
43. Butterfield JM, Lodise TP, Beegle S, et al. Pharmacokinetics and pharmacodynamics of extended-infusion piperacillin/tazobactam
in adult patients with cystic fibrosis-related acute pulmonary exacerbations. J Antimicrob Chemother. 2014;69(1):176-179.
https://doi.org/10.1093/jac/dkt300
44. Mahmoud SH, Shen C. Augmented Renal Clearance in Critical Illness: An Important Consideration in Drug Dosing. Pharmaceutics.
2017;9(3):36. https://doi.org/10.3390/pharmaceutics9030036
45. Carlier M, Carrette S, Roberts JA, et al. Meropenem and piperacillin/tazobactam prescribing in critically ill patients: does
augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used?
Crit Care. 2013;17(3):R84. https://doi.org/10.1186/cc12705
46. Yang H, Cui X, Ma Z, et al. Evaluation Outcomes Associated with Alternative Dosing Strategies for Piperacillin/Tazobactam: A
Systematic Review and Meta-Analysis. J Pharm Pharm Sci. 2016;19(2):274-289. https://doi.org/10.18433/jpps.v19i2.27517
47. Yang H, Zhang C, Zhou Q, et al. Clinical outcomes with alternative dosing strategies for piperacillin/tazobactam: a systematic
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Sep 27, 2023
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Extended infusion versus intermittent infusion of Piperacillin/ tazobactam: altering current methods to optimize future outcome. Pharm Pract (Granada) [Internet]. 2023 Sep. 27 [cited 2024 May 4];21(3):1-9. Available from: https://www.pharmacypractice.org/index.php/pp/article/view/2831
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