Piperacillin is an extended spectrum ureidopenicillin and is used to treat moderate-to-severe infections due to susceptible organisms. Piperacillin has been linked with idiosyncratic liver injury, but only rarely and in isolated case reports.
Piperacillin (pi" per a sil' in) is a fourth generation, extended spectum penicillin which is used for moderate-to-severe infections caused by susceptible agents, such as (but not limited to) Escherichia coli, Hemophilis influenzae, Listeria monocytogenesis, Neisseria gonorrhoeae, Proteus mirabilis, Salmonella, Shigella, Staphylococcus aureus (non-penicillinase producing), Staphylococcus epidermidis, and Streptococcus pneumoniae. Piperacillin was approved for use in the United States in 1981 and is generally reserved for severe infections requiring parenteral therapy. Piperacillin is available in parenteral form (intramuscular and intravenous) generically and under the trade name Pipracil. Piperacillin is often combined with a beta lactamase inhibitor (tazobactam) to prevent bacterial resistance. The recommended regimen is 2 to 4 grams daily in divided doses given every 4 to 6 hours usually for 5 to 7 days. Common side effects include headache, dizziness, nausea, diarrhea, constipation, skin rash and hypersensitivity reactions.
Patients on intravenous piperacillin may have transient and mild-to-moderate serum aminotransferase elevations in up to 12% of patients, but these are of little clinical significance and not more common than with comparative parenteral antibiotics. Hepatic injury was more commonly reported with mezlocillin, a related extended spectrum ureidopencillin which has been withdrawn from use. Rare instances of idiosyncratic liver injury have been reported in persons receiving piperacillin. The liver injury is typically cholestatic and can be severe, but is generally self-limited once piperacillin is stopped.
Mechanism of Injury
The cause of the liver injury associated with piperacillin use is probably hypersensitivity or allergy. Instances of cross reactivity with other penicillins and worsening of cholestasis with reintroduction of the agent have been reported.
Outcome and Management
In the few cases that have been described, patients have recovered within 1 to 3 months once the drug is stopped. Patients with piperacillin induced hepatitis should avoid reexposure to other penicillins and should take cephalosporins with caution.
References to the safety and potential hepatotoxicity of piperacillin are provided in the drug record on Piperacillin and Tazobactam.
Drug Class: Antiinfective Agents, Penicillins (Fourth Generation)
Other Drugs in the Class: Piperacillin and Tazobactam, Ticarcillin, Ticarcillin-Calvulanate
Case 1. Cholangiopathy with possible causation by piperacillin.
[Modified from: Schneider M, Helbling A, Zimmermann A, Krähenbühl S. Cholangiopathy after short-term administration of piperacillin and imipenem/cilastatin. Liver 2001; 21: 213-6].
|Medication:||Piperacillin, 1 gram IV bolus|
|Severity:||3+ (jaundiced and hospitalization)|
|Latency:||15 days to symptoms, 22 days to jaundice|
|Other medications:||Imipenem/cilastatin (4 gm daily IV for 3 days) and acetaminophen (4 gm daily orally for 3 days) in the post-operative period.|
|Time After Starting||Time After Stopping||ALT (U/L)||Alk P (U/L)||Bilirubin (mg/dL)||Other|
|Emergency surgery small bowel perforation: one dose of piperacillin given IV|
|4 days||3 days||83||39||Discharged|
|Developed fatigue followed by pruritus ~day 15 after surgery|
|21 days||20 days||345||201||0.9|
|22 days||21 days||654||416||2.9|
|25 days||24 days||669||559||4.7||Liver biopsy|
|35 days||34 days||210||531||1.2|
|DRUG||CAS REGISTRY NO||MOLECULAR FORMULA||STRUCTURE|