Piperacillin/tazobactam in modern clinical practice


  • Igor Bereznyakov Kharkiv Medical Academy of Postgraduate Education, Kharkiv




piperacillin/tazobactam, prolonged infusions, susceptibility to antibiotics, nosocomial pneumonias, Refex


Piperacillin/tazobactam represents a combination of the ureidopenicillin and the lactamase inhibitor. The antibiotic is the drug of choice for the treatment of severe infections, primarily in surgical and intensive care units. The area of clinical use of piperacillin/tazobactam includes intra-abdominal infections, skin and soft tissues infections, late nosocomial pneumonias, including ones in the context of the covid -19 pandemic, and infections of other localizations. The effectiveness of the intervention increases with intravenous administration of the drug by the method of prolonged infusions. A high susceptibility of most causative pathogens of wound infection to piperacillin/ tazobactam has been established in Ukraine (with the exception of Klebsiella spp. and non-fermenting bacteria). The drug can be used in patients with a history of allergic reactions to lactams; preliminary allergological testing is indicated only in cases of allergy to aminopenicillins and aminocephalosporins. The first domestic piperacillin/tazobactam under the name Refex is registered on the Ukrainian market.


Download data is not yet available.


ZOSYN. Highlights of prescribing information. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/050684s88s89s90_050750s37s38s39lbl.pdf

Craig WA. Basic pharmacodynamics of antibacterials with clinical applications to the use of β-lactams, glycopeptides, and linezolid. Infectious Disease Clinics. 2003 Sep 1;17(3):479-501. Available from: https://doi.org/10.1016/s0891-5520(03)00065-5

Drusano GL. Antimicrobial pharmacodynamics: critical interactions of'bug and drug'. Nature Reviews Microbiology. 2004 Apr;2(4):289-300. Available from: https://doi.org/10.1038/nrmicro862

McKinnon PS, Paladino JA, Schentag JJ. Evaluation of area under the inhibitory curve (AUIC) and time above the minimum inhibitory concentration (T> MIC) as predictors of outcome for cefepime and ceftazidime in serious bacterial infections. International journal of antimicrobial agents. 2008 Apr 1;31(4):345-51. Available from: https://doi.org/10.1016/j.ijantimicag.2007.12.009

Abdul-Aziz M, Lipman J, Mouton J, Hope W, Roberts J. Applying Pharmacokinetic/Pharmacodynamic Principles in Critically Ill Patients: Optimizing Efficacy and Reducing Resistance Development. Seminars in Respiratory and Critical Care Medicine [Internet]. Georg Thieme Verlag KG; 2015 Feb 2;36(1):136–53. Available from: https://doi.org/10.1055/s-0034-1398490

Roberts JA, Abdul-Aziz MH, Lipman J, Mouton JW, Vinks AA, Felton TW, Hope WW, Farkas A, Neely MN, Schentag JJ, Drusano G. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. The Lancet infectious diseases. 2014 Jun 1;14(6):498-509. Available from: https://doi.org/10.1016/s1473-3099(14)70036-2

Imani S, Buscher H, Day R, Gentili S, Jones GR, Marriott D, Norris R, Sandaradura I. An evaluation of risk factors to predict target concentration non-attainment in critically ill patients prior to empiric β-lactam therapy. European Journal of Clinical Microbiology & Infectious Diseases. 2018 Nov;37(11):2171-5. Available from: https://doi.org/10.1007/s10096-018-3357-9

Alobaid AS, Brinkmann A, Frey OR, Roehr AC, Luque S, Grau S, Wong G, Abdul-Aziz MH, Roberts MS, Lipman J, Roberts JA. What is the effect of obesity on piperacillin and meropenem trough concentrations in critically ill patients?. Journal of Antimicrobial Chemotherapy. 2016 Mar 1;71(3):696-702. Available from: https://doi.org/10.1093/jac/dkv412

Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive care medicine. 2021 Nov;47(11):1181-247. Available from: https://doi.org/10.1007/s00134-021-06506-y.

Fawaz S, Barton S, Nabhani-Gebara S. Comparing clinical outcomes of piperacillin-tazobactam administration and dosage strategies in critically ill adult patients: a systematic review and meta-analysis. BMC Infectious Diseases. 2020 Dec;20(1):430. Available from: https://doi.org/10.1186/s12879-020-05149-6

Yang H, Zhang C, Zhou Q, Wang Y, Chen L. Clinical outcomes with alternative dosing strategies for piperacillin/tazobactam: a systematic review and meta-analysis. PloS one. 2015 Jan 9;10(1):274–89. Available from: https://doi.org/10.1371/journal.pone.0116769

Abdulla A, Ewoldt TM, Purmer IM, Muller AE, Gommers D, Endeman H, Koch BC. A narrative review of predictors for β-lactam antibiotic exposure during empirical treatment in critically ill patients. Expert Opinion on Drug Metabolism & Toxicology. 2021 Apr 3;17(4):359-68. Available from: https://doi.org/10.1080/17425255.2021.1879049

Protocol of medical care for patients with community-acquired and nosocomial pneumonia in adults: etiology, pathogenesis, classification, diagnosis, antibacterial therapy March 19, 2007 № 128. Available from: http://www.ifp.kiev.ua/doc/staff/MOZ-128-19032007.pdf.

Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, Napolitano LM, O'Grady NP, Bartlett JG, Carratalà J, El Solh AA. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clinical Infectious Diseases. 2016 Sep 1;63(5):e61-111. Available from: https://doi.org/10.1093/cid/ciw353

Torres A, Niederman MS, Chastre J, Ewig S, Fernandez-Vandellos P, Hanberger H, Kollef M, Bassi GL, Luna CM, Martin-Loeches I, Paiva JA. International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT). European Respiratory Journal. 2017 Sep 1;50(3). Available from: https://doi.org/10.1183/13993003.00582-2017

Pneumonia (hospital-acquired): antimicrobial prescribing. NICEguideline [NG139]. Available from: https://www.nice.org.uk/guidance/ng139

Protocol "Provision of medical care for the treatment of coronavirus disease (covid-19)". Updated 11.11.2021. Available from: https://moz.gov.ua/article/ministry-mandates/nakaz-moz-ukraini-vid-11112021--2495-pro-vnesennja-zmin-do-protokolu-nadannja-medichnoi-dopomogi-dlja-likuvannja--koronavirusnoi-hvorobi-covid-19

Sfeir MM, Askin G, Christos P. Beta-lactam/beta-lactamase inhibitors versus carbapenem for bloodstream infections due to extended-spectrum beta-lactamase-producing Enterobacteriaceae: systematic review and meta-analysis. International journal of antimicrobial agents. 2018 Nov 1;52(5):554-70. Available from: https://doi.org/10.1016/j.ijantimicag.2018.07.021

Harris PN, Tambyah PA, Lye DC, Mo Y, Lee TH, Yilmaz M, Alenazi TH, Arabi Y, Falcone M, Bassetti M, Righi E. Effect of piperacillin-tazobactam vs meropenem on 30-day mortality for patients with E coli or Klebsiella pneumoniae bloodstream infection and ceftriaxone resistance: a randomized clinical trial. Jama. 2018 Sep 11;320(10):984-94. Available from: https://doi.org/10.1001/jama.2018.12163

Andersen MG, Thorsted A, Storgaard M, Kristoffersson AN, Friberg LE, Öbrink-Hansen K. Population pharmacokinetics of piperacillin in sepsis patients: should alternative dosing strategies be considered?. Antimicrobial agents and chemotherapy. 2018 Apr 26;62(5):e02306-17. Available from: https://doi.org/10.1128/AAC.02306-17

Pitout JD, Le P, Church DL, Gregson DB, Laupland KB. Antimicrobial susceptibility of well-characterised multiresistant CTX-M-producing Escherichia coli: failure of automated systems to detect resistance to piperacillin/tazobactam. International journal of antimicrobial agents. 2008 Oct 1;32(4):333-8. Available from: https://doi.org/10.1016/j.ijantimicag.2008.04.023

Henderson A, Paterson DL, Chatfield MD, Tambyah PA, Lye DC, De PP, Lin RT, Chew KL, Yin M, Lee TH, Yilmaz M. Association between minimum inhibitory concentration, beta-lactamase genes and mortality for patients treated with piperacillin/tazobactam or meropenem from the MERINO study. Clinical Infectious Diseases. 2021 Dec 1;73(11):e3842-50. Available from: https://doi.org/10.1093/cid/ciaa1479

Rodríguez-Baño J, Gutiérrez-Gutiérrez B, Pascual A. CON: Carbapenems are NOT necessary for all infections caused by ceftriaxone-resistant Enterobacterales. JAC-Antimicrobial Resistance. 2021 Mar;3(1). Available from: https://doi.org/10.1093/jacamr/dlaa112

Takimoto K, Wang Q, Suzuki D, Katayama M, Hayashi Y. Clinical efficacy of piperacillin/tazobactam in the treatment of complicated skin and soft tissue infections. Expert Opinion on Pharmacotherapy. 2017 Jul 3;18(10). Available from: https://doi.org/10.1080/14656566.2017.1341491

Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJ, Gorbach SL, Hirschmann JV, Kaplan SL, Montoya JG, Wade JC. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clinical infectious diseases. 2014 Jul 15;59(2):e10-52. Available from: https://doi.org/10.1093/cid/ciu296

Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, Armstrong DG, Deery HG, Embil JM, Joseph WS, Karchmer AW, Pinzur MS. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clinical infectious diseases. 2012 Jun 15;54(12):e132-73. Available from: https://doi.org/10.1093/cid/cis346

Diabetic foot problems: prevention and management. NICE guideline. Last updated 11 October 2019. Available from: www.nice.org.uk/guidance/ng19

Bereznyakov IG. The state of antibiotic resistance in Ukraine: the results of the AURA study [Stan antybiotykorezystentnosti v Ukrayini: rezulʹtaty doslidzhennya AURA.]. Health of Ukraine. 2020;5:21-3. [In Ukraine]

Macy E., Contreras R. Health care use and serious infection prevalence associated with penicillin “allergy” in hospitalized patients: a cohort study. J. Allergy Clin. Immunol. 2014;133:790-6. Available from: https://doi.org/10.1016/j.jaci.2013.09.021

Zagursky RJ, Pichichero ME. Cross-reactivity in β-lactam allergy. The Journal of Allergy and Clinical Immunology: In Practice. 2018 Jan 1;6(1):72-81. Available from: https://doi.org/10.1016/j.jaip.2017.08.027

Bereznyakov IG. Allergic reactions to antibiotics [Allerhycheskye reaktsyy na antybyotyky]. Kharkiv: GO UADVA. 2021. [In Ukraine]

Пиперациллин/тазобактам в современной клинической практике



How to Cite

Bereznyakov I. Piperacillin/tazobactam in modern clinical practice. prmd [Internet]. 2022 May 30 [cited 2022 Jul. 1];5(1):12-20. Available from: https://perioperative.org.ua/index.php/prtmdc/article/view/100



Original article