Antimicrobials

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)

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)

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

• Avoid in patients who have had documented allergic reactions to penicillin or cross-reactive cephalosporins see: Penicillin allergy and the use of beta-lactam antibiotics
• For use in Pregnancy and Breastfeeding, see Safe Use of Antibacterial Agents: Pregnancy & Breastfeeding section
• Increased risk of nephrotoxicity when administered concomitantly with vancomycin⁴

• 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)

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

Renal Insufficiency:

• For preparation/administration, see IV drug monograph

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.