Piperacillin

Antibiotic Class:

Penicillin (ureidopenicillin and piperazine penicillin)

Antimicrobial Spectrum:

Gram-positive:  Streptococcus spp., Enterococcus, Listeria monocytogenes

Gram-negative:  Pseudomonas aeruginosa, Klebsiella, Serratia, Enterobacter, Enterococcus, H. influenzae, E. coli, Proteus mirabilis, Salmonella spp., Shigella spp.

Mechanism of Action:

Exerts bactericidal activity via inhibition of bacterial cell wall synthesis by binding one or more of the penicillin binding proteins (PBPs).  Exerts bacterial autolytic effect by inhibition of certain PBPs related to the activation of a bacterial autolytic process. 

Pharmacodynamics:

Penicillins produce time-dependent killing

Pharmacokinetics:

Cmax: 240mcg/ml; Half-life: 1 hour; Table 6

Adverse Effects:

Hematologic:  anemia, thrombocytopenia, neutropenia, agranulocytosis

CNS:  seizures, headache, dizziness, fatigue

Endocrine:  hypokalemia

Renal:  nephrotoxicity, interstitial nephritis

Hepatic:  transient increases in transaminases

Other:  Jarisch-Herxheimer Reaction (fever, chills, sweating, tachycardia, hyperventilation, flushing, and myalgia)

Dosage:

Adult: 3-4g IV q4-6h

Pediatric: 1 month -12 years: 50 mg/kg q4h

Disease state based dosing:

Renal failure:  CrCL 20-40 mL/min: 3-4g q8h

CrCL < 20 mL/min: 3-4g q12h

Supplement after Hemodialysis: 1g

Contraindications/Warnings/Precautions:

Contraindications:  hypersensitivity to piperacillin or other penicillins

Precautions: 

• Cephalosporin hypersensitivity
• Patients with mononucleosis are more likely to develop a skin rash
• Coagulation abnormalities (bleeding time, platelet disorders)
• Patients with electrolyte and fluid abnormalities (contains 1.85 mEq of sodium per gram)

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, signs and symptoms of infection

Toxic:  Periodic CBC, urinalysis, BUN, SCr, AST and ALT, diarrhea, skin rash

Brand names/Manufacturer: 

         HUBERCILINA (ICN - SPAIN)

         PIPERACILLIN (Mayne CANADA)

         PIPRACIL (Wyeth - CANADA)

         PIPRIL (Lederle - AUSTRALIA)