Piperacillin is a broad-spectrum Beta-lactam antibiotic that is usually administered in combination with tazobactam for the treatment of Gram-Negative Infections.

Piperacillin Uses:

Note: Not approved in the US

• Infection:

  • Treatment of infection caused by susceptible gram-negative/gram-positive aerobic and anaerobic bacteria including:
    • intra-abdominal infections,
    • septicemia,
    • lower respiratory tract infections,
    • skin and soft tissue infections,
    • bone and joint infections,
    • gynecological infections,
    • urinary tract infections (complicated and uncomplicated), and
    • uncomplicated urethritis
    • may also be used to treat mixed infections due to susceptible streptococci

Piperacillin dose in Adults

Piperacillin dose in the treatment of Community-acquired pneumonia:

• IM, IV: Usual dosage: 6 to 8 g per day (100 to 125 mg/kg daily) in divided doses every 6 to 12 hours

Piperacillin dose in the treatment of severe infections (eg, gynecologic, intra-abdominal, nosocomial pneumonia, septicemia, skin/soft tissue):

• IV: Usual dosage: 12 to 18 g per day (200 to 300 mg/kg daily) in divided doses every 4 to 6 hours (maximum: 24 g daily)

Piperacillin dose in the treatment of gonococcal, uncomplicated Urethritis:

• IM: 2 g once (Note: Administer probenecid 30 minutes prior to piperacillin)

Piperacillin dose in the treatment of complicated Urinary tract infection:

• IV: Usual dosage: 8 to 16 g per day (125 to 200 mg/kg daily) in divided doses every 6 to 8 hours

Piperacillin dose in the treatment of uncomplicated Urinary tract infection:

• IM, IV: Usual dosage: 6 to 8 g per day (100 to 125 mg/kg daily) in divided doses every 6 to 12 hours

Piperacillin dose in Childrens

Refer to adults dosing.

Piperacillin Pregnancy Risk Category: B

• Piperacillin crosses over the placenta, and is distributed into the amniotic liquid
• Some pharmacokinetic parameters for piperacillin could be affected by pregnancy-induced physiological changes
• Term-wise, piperacillin's apparent volume distribution is greater and its peak concentrations are much lower.
• It is not unusual for total clearance to rise over time
• These changes continue well into the first postpartum period.

Piperacillin can be used during breastfeeding

• Breast milk contains small amounts of piperacillin.
• Piperacillin should not be administered to nursing mothers, according to the manufacturer.
• Modification of the bowel flora could also be a non-dose-related effect.

Piperacillin Dose in Kidney Disease:

• CrCl >40 mL/minute or serum creatinine 1.5 to 3 mg/dL:

  • No dosage adjustment is necessary.

• CrCl 20-40 mL/minute or serum creatinine 3.1 to 5 mg/dL:

  • uncomplicated Urinary tract infection:

    • No dosage adjustment is necessary.

  • complicated Urinary tract infection:

    • 3 g every 8 hours

  • Severe systemic infection:

    • 4 g every 8 hours

• CrCl <20 mL/minute or serum creatinine >5 mg/dL:

  • Urinary tract infection (complicated/uncomplicated):

    • 3 g every 12 hours

  • Severe systemic infection:

    • 4 g every 12 hours

• Hemodialysis:

  • Severe systemic infection: 2 g every 8 hours;
  • administer 1 g supplemental dose after each dialysis session; dialyzable (30% to 50%)

Piperacillin Dose in Liver Disease:

• No dosage adjustment provided in drug manufacturer’s labeling.

Side effects of Piperacillin:

• Cardiovascular:

  • Local Thrombophlebitis

• Central Nervous System:

  • Confusion
  • Drowsiness
  • Myoclonus
  • Seizure

• Dermatologic:

  • Skin Rash
  • Toxic Epidermal Necrolysis
  • Urticaria

• Endocrine & Metabolic:

  • Electrolyte Disturbance
  • Hypokalemia

• Hematologic & Oncologic:

  • Abnormal Platelet Aggregation (High Doses)
  • Agranulocytosis
  • Hemolytic Anemia
  • Pancytopenia
  • Positive Direct Coombs Test
  • Prolonged Prothrombin Time (High Doses)

• Hypersensitivity:

  • Anaphylaxis
  • Hypersensitivity Reaction

• Immunologic:

  • Jarisch-Herxheimer Reaction

• Renal:

  • Acute Interstitial Nephritis
  • Acute Renal Failure

• Miscellaneous:

  • Fever

Contraindications to Piperacillin:

• Hypersensitivity/Allergy to any of the penicillins and/or cephalosporins or any component of the formulation;
• Hypersensitivity to local anesthetics (amide-type)

Warnings and precautions

• Anaphylactoid reactions and hypersensitivity reactions

  • Patients on penicillin therapy have had severe and sometimes fatal anaphylactic reactions.
  • This is especially true if they have a history of beta-lactam hypersensitivity or sensitivity to multiple allergens.
  • Asthmatic patients should be cautious.
  • If hypersensitivity develops, discontinue use and seek emergency treatment.

• Bleeding disorders:

  • Patients with kidney impairment are more susceptible to bleeding disorders.
  • If bleeding or thrombocytopenia occurs, discontinue use.

• Leukopenia, neutropenia

  • Leukopenia or neutropenia can be caused by prolonged use.

• Superinfection

  • Prolonged use may cause fungal or bacterial superinfection, including C.difficile-associated diarrhea (CDAD) and pseudomembranous colitis;
  • CDAD was reported within 2 months of receiving antibiotic therapy.

• Cardiovascular disease

  • Take caution when using this product, especially if you are a sodium-restricted patient on long-term therapy. The formulation contains 42.5 mg sodium per gram.
  • With a longer treatment duration, monitor electrolyte status and cardiac function.

• Cystic Fibrosis:

  • Patients with cystic Fibrosis have been known to experience an increase in fever and rash.

• Infectious mononucleosis

  • Infectious mononucleosis patients have experienced a rash after receiving therapy with penicillins, such as amoxicillin and ampicillin.

• Renal impairment

  • Patients with renal impairment should be cautious due to the sodium load and adverse effects (hematologic and neuropsychological changes). Dosage adjustment is recommended.

• Seizure disorders:

  • Seizures can be increased by high drug levels, especially in the case of renal impairment.
  • Patients with a history of seizure disorder should be cautious.

• Syphilis:

  • Patients receiving high-dose antimicrobial therapy for gonorrhea may experience symptoms of syphilis that are delayed or masked.
  • Patients with gonorrhea need to be tested for syphilis before initiating antimicrobial therapy. If syphilis has been suspected, serologic testing should continue for at least four months.

Piperacillin (United States: Not available): Drug Interaction

Monitoring Parameters:

• Observe for signs and symptoms of anaphylaxis during administration first dose;
• with extended therapy consider monitoring of electrolytes and cardiac status (patients with impaired cardiac function),
• serum creatinine, BUN,
• hepatic function, and
• CBC.

How to administer Piperacillin?

• IV: Rapid administration can lead to seizures.
• Administer by IV injection over 3 to 5 minutes or by intermittent infusion over 20 minutes to 2 hours.
• IM: IM injection should be administered into the upper outer quadrant of the buttocks.
• Do not administer more than 2 g per IM injection site.

Mechanism of action of Piperacillin:

• Attaches to penicillin-binding proteins (PBPs) and inhibits the synthesis of the bacterial cells wall. This inhibits the final step in peptidoglycan synthesis in bacterial cells walls.
• Bacteria eventually lyse because of ongoing underlying activity cell wall autolytic enzymes, i.e. autolysins or murein hydrolases. Cell wall assembly is currently on hold (arrested).

Absorption:

• IM: Rapid

Protein binding:

• ~16%

Half-life elimination (dose-dependent; prolonged with renal impairment):

• Adults: ~1 hour (decreased in patients with cystic fibrosis)

Time to peak, serum:

• IM: 30 minutes

Excretion:

• Primarily urine;
• partially feces

International Brands of Piperacillin:

• Acopex
• Isipen
• Pentcillin
• Peracillin
• Peracin
• Picillina
• Pipcil
• Piperacillin
• Pipracil
• Pipraks
• Pipril
• Prisutomycin

Piperacillin Brand Names in Pakistan: