Piperacillin

Usage

Piperacillin is a semisynthetic, broad-spectrum, extended-spectrum, β-lactam antibiotic belonging to the ureidopenicillin subclass of penicillins. It is primarily used to treat bacterial infections caused by susceptible gram-positive, gram-negative, aerobic, and anaerobic organisms. Piperacillin is particularly effective against Pseudomonas aeruginosa, making it a valuable treatment option for infections caused by this bacterium. Piperacillin is often used in combination with the β-lactamase inhibitor tazobactam to enhance its activity against bacteria that produce β-lactamase enzymes, which break down penicillins.

It’s pharmacological classification is antibiotic.

The mechanism of action of piperacillin involves inhibiting bacterial cell wall synthesis by binding to and inactivating penicillin-binding proteins (PBPs). These PBPs are essential enzymes involved in the final stages of peptidoglycan synthesis, a crucial component of the bacterial cell wall. By inhibiting PBPs, piperacillin disrupts cell wall integrity, leading to bacterial cell death.

Alternate Names

Piperacillin is often administered as piperacillin sodium. It is frequently combined with tazobactam and marketed under various brand names, including PipTaz, Tazocin, and Zosyn.

How It Works

Pharmacodynamics: Piperacillin exerts its bactericidal effect by inhibiting bacterial cell wall synthesis. Its extended spectrum of activity encompasses many gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. The addition of tazobactam extends its spectrum further by inhibiting a wide range of beta-lactamases, including many TEM, SHV, and OXA enzymes.

Pharmacokinetics:

• Absorption: Piperacillin is administered intravenously (IV) or intramuscularly (IM). It achieves peak serum concentrations rapidly after IV administration.
• Distribution: It distributes widely throughout the body, reaching therapeutic concentrations in various tissues and fluids.
• Metabolism: Piperacillin undergoes minimal metabolism in the liver.
• Elimination: It’s primarily eliminated by the kidneys through glomerular filtration and tubular secretion, with a small portion excreted in the bile. The elimination half-life is typically 0.8-1.2 hours and may be prolonged in patients with renal impairment.

Mode of Action: Piperacillin’s mode of action is time-dependent, meaning its efficacy is related to the time the serum concentration remains above the minimum inhibitory concentration (MIC) of the target bacteria.

Receptor Binding/Enzyme Inhibition: Piperacillin exerts its antibacterial effect by binding to and inhibiting bacterial penicillin-binding proteins (PBPs), essential for cell wall synthesis. Tazobactam inhibits bacterial beta-lactamases, thus protecting piperacillin from degradation.

Dosage

Standard Dosage

Adults:

The standard intravenous dose is 3.375 g every six hours (q6h) or 4 g every eight hours (q8h), infused over 30 minutes. For more severe infections, dosages up to 18 g/day in divided doses can be used. Intramuscular administration is less common.

Children:

• 2-9 months: 80 mg/kg (based on the piperacillin component) every six to eight hours.
• >9 months (≤40 kg): 100 mg/kg every eight hours.
• >9 months (>40 kg): Adult dose.
• Neonates (≤30 weeks postmenstrual age): 100 mg/kg every 8 hours.
• Neonates (>30 weeks postmenstrual age): 80 mg/kg every 6 hours.

Pediatric doses should not exceed the maximum adult dose.

Special Cases:

• Elderly Patients: Dosage adjustment may be required based on renal function.
• Patients with Renal Impairment: Dosage should be reduced based on creatinine clearance (CrCl). For CrCl < 20 mL/min, 2.25 g every 8 to 12 hours is recommended. Hemodialysis patients require supplemental doses.
• Patients with Hepatic Dysfunction: No dosage adjustment is typically needed.
• Patients with Comorbid Conditions: Individualized dosing may be necessary.

Clinical Use Cases:

• Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use/Emergency Situations: Dosing guidelines are the same as for standard severe infections, with dosage adjustments as needed based on renal function and patient condition. The regimen chosen (every 6 or 8 hours) will depend on local protocols.

Dosage Adjustments:

Dosage adjustments are primarily based on creatinine clearance. Refer to the “Special Cases” section for more details.

Side Effects

Common Side Effects:

Diarrhea, nausea, constipation, headache, rash, injection site reactions (pain, phlebitis).

Rare but Serious Side Effects:

Allergic reactions (including anaphylaxis), Clostridium difficile associated diarrhea, neutropenia, thrombocytopenia, seizures (especially in patients with renal impairment), pseudomembranous colitis, acute interstitial nephritis.

Long-Term Effects:

Prolonged use might increase the risk of antibiotic resistance and superinfections (like fungal infections).

Adverse Drug Reactions (ADR):

Anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Contraindications:

Hypersensitivity to piperacillin, tazobactam, or other penicillins/cephalosporins.

Drug Interactions:

• Probenecid: Increases piperacillin serum levels.
• Aminoglycosides: Synergistic against certain bacteria but should be administered separately due to in vitro inactivation.
• Anticoagulants: Increased risk of bleeding.
• Methotrexate: Reduced methotrexate clearance.
• Vecuronium: Prolonged neuromuscular blockade.

Pregnancy and Breastfeeding:

Piperacillin is classified as Pregnancy Category B. While animal studies show no evidence of fetal harm, it should be used during pregnancy only if clearly needed. It is excreted in breast milk in low concentrations, and caution is advised during breastfeeding.

Drug Profile Summary:

• Mechanism of Action: Inhibits bacterial cell wall synthesis.
• Side Effects: Diarrhea, nausea, rash, allergic reactions.
• Contraindications: Hypersensitivity to penicillins/cephalosporins.
• Drug Interactions: Probenecid, aminoglycosides, anticoagulants, methotrexate, vecuronium.
• Pregnancy & Breastfeeding: Category B; caution advised during breastfeeding.
• Dosage: See dosage section above.
• Monitoring Parameters: Renal function, signs of infection, complete blood count, liver function tests.

Popular Combinations

Piperacillin/Tazobactam is commonly used alone, or with an aminoglycoside (e.g., gentamicin, tobramycin, or amikacin) for severe infections, especially those caused by Pseudomonas aeruginosa.

Precautions:

Assess renal function before and during treatment. Monitor for signs of allergic reactions, superinfections, and bleeding. Careful administration is required in patients with seizures and cystic fibrosis. Avoid alcohol.

FAQs

Q1: What is the recommended dosage for Piperacillin/Tazobactam?

A: See the detailed dosage section above.

Q2: How is Piperacillin/Tazobactam administered?

A: It’s administered intravenously (IV), typically infused over 30 minutes. Intramuscular (IM) administration is less common.

Q3: What are the most common side effects?

A: Diarrhea, nausea, constipation, headache, and rash.

Q4: What are the serious adverse reactions to watch out for?

A: Allergic reactions (anaphylaxis), Clostridium difficile diarrhea, and neutropenia.

Q5: Can Piperacillin/Tazobactam be used in pregnant or breastfeeding women?

A: It should be used cautiously during pregnancy only if the benefits outweigh the potential risks. It is excreted in breast milk in low concentrations; caution is advised.

Q6: What are the major drug interactions with Piperacillin/Tazobactam?

A: Probenecid, aminoglycosides, anticoagulants, methotrexate, vecuronium.

Q7: What should be monitored in patients receiving Piperacillin/Tazobactam?

A: Renal function, signs and symptoms of infection, complete blood count, and liver function tests.

Q8: How does tazobactam enhance the activity of piperacillin?

A: Tazobactam inhibits bacterial β-lactamases, protecting piperacillin from being broken down and enhancing its efficacy against bacteria producing these enzymes.

Q9: What infections are commonly treated with Piperacillin/Tazobactam?

A: Intra-abdominal infections, nosocomial pneumonia, skin and skin structure infections, female pelvic infections, and community-acquired pneumonia. It is also effective for bacteremia, febrile neutropenia, and bone and joint infections.

Q10: Is there a difference in dose or frequency for different infections?

A: The total daily dose and the frequency of administration (every 6 or 8 hours) are determined based on the severity and type of infection, as well as individual patient factors such as renal function.