Piperacillin/Tazobactam

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General

  • Type: Anti-Pseudomonal Penicillin
  • Dosage Forms: 2.25gm vial, 3.375gm vial, 4.5gm vial, 40.5gm bulk bottle (Powder for reconstitution)
  • Common Trade Names: Zosyn

Adult Dosing

General

  • 3.375 g IV q6 hours
  • Alt: 4.5 g q6-8 hours
  • Max: 18 g/day

Extended Interval Dosing

  • 3.375 g IV infused over 4 hours q8 hours
    • Off-label: may reduce costs without sacrificing efficacy[1][2]

Diverticulitis

  • 3.375 g IV q6 hours x 7-10 days

Pneumonia

  • CAP
    • 3.375 g IV q6 hours x 7-10 days
    • Only for P. aeruginosa caused or from aspiration[3]
  • Nosocomial
    • 4.5 g IV q6 hours or 3.375 g IV q4 hours x 7-14 days
    • + aminoglycoside or antipseudomonal fluoroquinolone

Pediatric Dosing[4]

A Piperacillin/Taxobactam 3.375g vial contains 3g piperacillin and 0.375g tazobactam (8:1 ratio)

General

  • <2 months
    • 100mg piperacillin/kg/dose IV q6 hours
  • 2-9 months
    • 80mg piperacillin/kg/dose IV q8 hours
  • >9 months
    • 100mg piperacillin/kg/dose q8 hours
  • Max: 16 g/day

Appendicitis and/or Peritonitis

  • 2-9 months
    • 80mg piperacillin/kg/dose IV q8 hours
  • >9 months
    • ≤40 kg: 100mg piperacillin/kg/dose IV q8 hours
    • >40 kg: 3.375g (3000mg piperacillin) IV q6 hours
  • Max: 16 g/day

Cystic Fibrosis, Pseudomonal Infection

  • 240-400mg piperacillin/kg/day IV divided q8 hours;
    • Consider higher dose: 450-600mg/kg/day IV divided q4-6 hours[5]

Special Populations

  • Pregnancy:
  • Lactation:
  • Renal Dosing
    • Adult - all indications[6][7]
      • CrCl 20-40: 2.25 g q6h (3.375 g q6h if HCAP)
      • CrCl < 20: 2.25 g q8h (2.25 g q6h if HCAP)
      • HD: 2.25 g q12h (2.25 g q8h if HCAP), both PLUS 0.75 g supplement after each dialysis
      • PD: 2.25 g q12h (2.25 g q8h if HCAP)
    • Pediatric
  • Hepatic Dosing - no change

Contraindications

  • Allergy to class/drug
  • Caution
    • Non-anaphylactic hypersensitivity to beta-lactams
    • Asthma, cystic fibrosis
    • Recent antibiotic-associated colitis
    • Seizure disorder
    • Renal impairement
    • Sodium restriction
    • Hypokalemia
    • Bleeding risk

Adverse Reactions

Serious

Common

Pharmacology

  • Half-life:
    • Pipercillin: 30-90 min
    • Tazobactam: 0.7-1.2h
  • Metabolism:
    • Pipercillin: Liver minimally
    • Tazobactam: Liver
  • Excretion:
    • Pipercillin: Urine 68%
    • Tazobactam: Urine primarily
  • Mechanism of Action:
    • Pipercillin: Inhibits cell wall mucopeptide synthesis
    • Tazobactam: Inhibits beta-lactamases

Antibiotic Sensitivities[8]

Group Organism Sensitivity
Gram Positive Strep. Group A, B, C, G S
Strep. Pneumoniae S
Viridans strep I
Strep. anginosus gp S
Enterococcus faecalis S
Enterococcus faecium I
MSSA S
MRSA R
CA-MRSA R
Staph. Epidermidis S
C. jeikeium X1
L. monocytogenes X2
Gram Negatives N. gonorrhoeae X2
N. meningitidis S
Moraxella catarrhalis S
H. influenzae S
E. coli S
Klebsiella sp S
E. coli/Klebsiella ESBL+ R
E coli/Klebsiella KPC+ R
Enterobacter sp, AmpC neg S
Enterobacter sp, AmpC pos S
Serratia sp S
Serratia marcescens X1
Salmonella sp S
Shigella sp S
Proteus mirabilis S
Proteus vulgaris S
Providencia sp. S
Morganella sp. S
Citrobacter freundii S
Citrobacter diversus S
Citrobacter sp. S
Aeromonas sp S
Acinetobacter sp. I
Pseudomonas aeruginosa S
Burkholderia cepacia X1
Stenotrophomonas maltophilia I
Yersinia enterocolitica X1
Francisella tularensis X1
Brucella sp. X1
Legionella sp. R
Pasteurella multocida X1
Haemophilus ducreyi X1
Vibrio vulnificus X1
Misc Chlamydophila sp R
Mycoplasm pneumoniae R
Rickettsia sp X1
Mycobacterium avium X1
Anaerobes Actinomyces X1
Bacteroides fragilis S
Prevotella melaninogenica S
Clostridium difficile X1
Clostridium (not difficile) S
Fusobacterium necrophorum S
Peptostreptococcus sp. S

Key

  • S susceptible/sensitive (usually)
  • I intermediate (variably susceptible/resistant)
  • R resistant (or not effective clinically)
  • S+ synergistic with cell wall antibiotics
  • U sensitive for UTI only (non systemic infection)
  • X1 no data
  • X2 active in vitro, but not used clinically
  • X3 active in vitro, but not clinically effective for Group A strep pharyngitis or infections due to E. faecalis
  • X4 active in vitro, but not clinically effective for strep pneumonia

See Also

References

  1. Shea KM, Cheatham SC, Smith DW, Wack MF, Sowinski KM, Kays MB. Comparative pharmacodynamics of intermittent and prolonged infusions of piperacillin/tazobactamusing Monte Carlo simulations and steady-state pharmacokinetic data from hospitalized patients. Ann Pharmacother. 2009;43(11):1747-54.
  2. Kaufman SE, Donnell RW, Hickey WS. Rationale and evidence for extended infusion of piperacillin-tazobactam. Am J Health Syst Pharm. 2011 Aug 15;68(16):1521-6.
  3. Mandell, 2007
  4. Red Book, 2012
  5. Zobell JT, Waters CD, Young DC, et al, "Optimization of Anti-Pseudomonal Antibiotics for Cystic Fibrosis Pulmonary Exacerbations: II. Cephalosporins and Penicillins," Pediatr Pulmonol, 2013, 48(2):107-22. PubMed 22949297
  6. GlobalRPH. Piperacillin/Tazobactam - Zosyn® - Renal Dosing. http://www.globalrph.com/piperacillin-tazobactam_renal.htm
  7. Epocrates. Zosyn - Entire Monograph. https://online.epocrates.com/u/10a1657/Zosyn
  8. Sanford Guide to Antimicrobial Therapy 2014