Piperacillin

Piperacillin is a broad-spectrum β-lactam antibiotic in the ureidopenicillin class. The chemical structure of piperacillin and other ureidopenicillins contains a polar side chain that increases penetration into Gram-negative bacteria and reduces susceptibility to cleavage by Gram-negative beta-lactamase enzymes. These properties confer activity against the important hospital pathogen Pseudomonas aeruginosa. Therefore, piperacillin is sometimes referred to as "anti-Pseudomonas penicillin". Piperacillin is used almost exclusively in combination with the beta-lactamase inhibitor tazobactam to treat serious hospital-acquired infections.

Pharmacodynamics

By binding to specific penicillin-binding proteins (PBPs) located within the bacterial cell wall, piperacillin inhibits the third and final stage of bacterial cell wall synthesis. Cell lysis (dissolution of the cell) is then mediated by bacterial cell wall enzymes, also called autolysins. This stops bacterial proliferation and destroys the pathogen.

Pharmacokinetics

Piperacillin is not orally absorbed and therefore must be administered by intravenous or intramuscular injection. It is largely unmetabolized and excreted unchanged by the kidneys. The half-life is between 30 and 70 minutes.

Drug Interactions

Some compounds that may interfere with the bactericidal activity of piperacillin are chloramphenicol, macrolides, and sulfonamides.

Side effects

Common side effects associated with the administration of piperacillin-tazobactam include:

• Gastrointestinal: constipation, diarrhea, nausea, vomiting.
• Dermatological: erythema, pain, phlebitis, rash
• Neurological: headache, insomnia

Prolonged piperacillin-tazobactam therapy has been associated with the possible development of hematologic adverse reactions such as leukopenia (16.3%), neutropenia (10%), and eosinophilia (10%) in adult patients.

Toxicological Data

LD50 (rat, oral): > 10 g-kg-1