Piperacillin/tazobactam

Staphylococcus aureus (methicillin susceptible), Coagulase negative Staphylococci, Streptococcus pneumoniae (penicillin susceptible), Streptococcus spp., Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitides, Neisseria gonorrhoeae, Enterobacteriaceae, E. coli, Pseudomonas aeruginosa

Mechanism of Action:

The beta-lactamase inhibitors are recognized as substrates for the beta-lactamases produced by bacteria. This allows the actual beta-lactams to attack the bacterial cell wall by binding to penicillin binding proteins

Pharmacodynamics:

Time dependent killer (Time > MIC)

Pharmacokinetics:

(of the tazobactam)

Dose 200mg: Cmax: 29 mcg/L; Protein binding: 20-23%; Volume of distribution: 0.18-0.33L/kg; Table 5

Adverse Effects:

No new adverse effects are seen as a result of adding beta-lactamase inhibitors to beta-lactam antibiotics. The adverse reactions would remain the same for the parent compound

Dosage:

IV: Complete listing on Table 6

Dosing in adults:

Mild/Moderate: 2.25-3.375g q6h

Severe: 3.375-4.5g q6h

Dosing in pediatrics:

Not indicated in children < 12 years of age

Table 8

Disease state based dosing:

Renal failure: CrCl > 40mL/min: 3.375g q4-6h

CrCl 20-40mL/min: 2.25g q6h

CrCl < 20mL/min: 2.25g q8h

Hepatic failure: Dosage adjustment not necessary

Table 9

Dosing during Continuous Renal Replacement Therapy

CVVH (Continuous venovenous hemofiltration): 2.25g IV q6h

CVVHD (Continuous venovenous hemodialysis): 2.25-3.375g IV q6h

CVVHDF (Continuous venovenous hemodiafiltration) 2.25g-3.375g IV q6h

Note: CVVH is mainly for fluid removal alone. Many institutions will employ more CVVHD or CVVHDF which combine dialysis with fluid removal.

Contraindications/Warnings/Precautions:

Precautions: hypersensitivity to penicillins, history of gastrointestinal disease, particularly colitis, renal impairment

Drug Interactions:

Live Typhoid Vaccine - decreased immunological response to the typhoid vaccine

Methotrexate – increased methotrexate toxicity

Probenecid - increased piperacillin levels

Vecuronium - enhanced and/or prolonged neuromuscular blockade which may lead to respiratory depression and paralysis

Pregnancy:

Category B: No evidence of risk in humans but studies inadequate.

Monitoring Requirements:

Therapeutic: Culture and sensitivities, serum levels, signs and symptoms of infection, white blood cell count

Toxic: Urinalysis, BUN, SCr, AST and ALT, skin rash, Neutropenia and leukopenia,

Brand names/Manufacturer:

Zosyn/Wyeth pharmaceuticals