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Antimicrobials

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Piperacillin-tazobactam

Guidelines for use

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1. Spectrum of Activity

Active against:

  • Streptococci
  • Most strains of Staphylococcus aureus (excluding MRSA)
  • Enterococcus faecalis
  • Haemophilus influenzae
  • Most strains of Coli, Klebsiella spp., P. Mirabilis, Citrobacter koseri
  • Most strains of Pseudomonas aeruginosa
  • Many organisms that are of low risk for AmpC beta-lactamase production (Serratia marcescens. Providencia spp, Morganella morganii)1
  • Most anaerobes, including: Bacteroides, Clostridium spp., Peptostreptococcus, Peptococcus, Fusobacterium

Not active against:

  • MRSA
  • Enterococcus faecium
  • Extended-spectrum beta-lactamase (ESBL) producing organisms2
  • Organisms that are of high risk for AmpC beta-lactamase production (Enterobacter, Citrobacter freundii, Klebsiella aerogenes)1
  • Atypical organisms (Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila)

    2. Clinical Use

    Appropriate Uses:

    • Nosocomial pneumonia in patients with risk factors for Pseudomonas aeruginosa infection), including Ventilator Associated Pneumonia
    • High severity health care associated intra-abdominal infections
    • Diabetic ulcers with associated acute osteomyelitis
    • Necrotizing skin and soft tissue infections
    • Febrile Neutropenia

    Inappropriate Uses:

    • Surgical prophylaxis
    • CNS infections due to decreased penetration of tazobactam
    • Treatment of infections caused by organisms susceptible to more narrow spectrum options (e.g., intra-abdominal, skin and soft tissue)

    3. Significant Drug Interactions

    • Methotrexate: May increase serum concentrations, with higher doses of methotrexate other antibiotics should be used.3

    4. Precautions

    5. Adverse Effects

    • Nausea, abdominal pain, vomiting, diarrhea
    • Skin rash
    • Hypersensitivity reactions including anaphylaxis
    • Phlebitis at site of IV infusion
    • Rarely: interstitial nephritis; blood dyscrasias; elevated liver enzymes; seizures (drug accumulation in renal insufficiency)

    6. Dosage

    • Usual dosage:3.375 g q6h
    • Pseudomonas dosage:4.5 g q6h

    Renal Insufficiency:

    CREATININE CLEARANCE (mL/min) USUAL DOSAGE PSEUDOMONAS DOSAGE
    10 to 29 3.375 g q8h 4.5 g q8h
    < 10 or PD 3.375 g q12h 4.5 g q12h
    Hemodialysis (HD)

    3.375 g q12h

    On dialysis days, give one of the doses towards the end of HD

    4.5 g q12h

    On dialysis days, give one of the doses towards the end of HD
    Continuous Renal Replacement Therapy (CRRT) 3.375 g q6h 4.5 g q6h
    Sustained Low
    Efficiency Dialysis (SLED)5    		 3.375 g q12-8h* 4.5 g q12-8h*

    *Dose will be dependent on severity of illness and duration/frequency of SLED dialysis sessions

    6. Administration

    3. References

    1. Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America Guidance on the Treatment of AmpC β-lactamase-Producing Enterobacterales, Carbapenem-Resistant Acinetobacter baumannii, and Stenotrophomonas maltophilia Infections. Infectious Diseases Society of America 2022; Version 2.0. Available at https://www.idsociety.org/practice-guideline/amr-guidance-2.0/.
    2. Harris PNA, Tambyah PA, Lye DC, et al. 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 [published correction appears in JAMA. 2019 Jun 18;321(23):2370]. JAMA. 2018;320(10):984-994.
    3. Zarychanski R, Wlodarczyk K, Ariano R, et al. Pharmacokinetic interaction between methotrexate and piperacillin/tazobactam resulting in prolonged toxic concentrations of methotrexate. J Antimicrob Chemother. 2006;58(1):228-230
    4. Hammond DA, Smith MN, Li C, Hayes SM, Lusardi K, Bookstaver PB. Systematic Review and Meta-Analysis of Acute Kidney Injury Associated with Concomitant Vancomycin and Piperacillin/tazobactam. Clin Infect Dis. 2017 Mar 1;64(5):666-674. doi: 10.1093/cid/ciw811. Epub 2016 Dec 10. PMID: 27940946.
    5. Brown P, Battistella M. Principles of Drug Dosing in Sustained Low Efficiency Dialysis (SLED) and Review of Antimicrobial Dosing Literature. Pharmacy (Basel). 2020 Mar 9;8(1):33. doi: 10.3390/pharmacy8010033. PMID: 32182835; PMCID: PMC7151685.

    Last updated: May 18, 2023