Cefpirome

Usage

Cefpirome is a fourth-generation cephalosporin antibiotic indicated for the treatment of moderate to severe bacterial infections. These infections may include lower respiratory tract infections (e.g., pneumonia, bronchitis), complicated urinary tract infections (both upper and lower), bacteremia/septicemia, skin and soft tissue infections, and infections in neutropenic and immunocompromised patients. It is particularly useful in intensive care settings for severe infections.

Pharmacological Classification: Antibiotic

Mechanism of Action: Cefpirome exerts its bactericidal effect by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs), which are crucial enzymes involved in the final transpeptidation step of peptidoglycan synthesis. This binding disrupts the cross-linking of peptidoglycans, leading to cell wall instability and ultimately bacterial cell death.

Alternate Names

Cefpirome sulfate is the chemical name, but it’s generally known as Cefpirome in clinical practice. Brand names include Cefir, Cefnos, Cefrin, Cefron, Ethirom, Morcef, Romicef, Sopirom, Bactirom, Broact, Cef-4, Cefrom, Interome, Keiten, Lanpirome, Nufirom, Xenoprom, Yarox, Genpirome, and Maxipime (cefepime - similar cephalosporin, not Cefpirome).

How It Works

Pharmacodynamics: Cefpirome demonstrates a time-dependent killing action, meaning its efficacy correlates with the duration for which its free concentration exceeds the minimum inhibitory concentration (MIC) of the target bacteria. It has broad-spectrum activity against both Gram-positive and Gram-negative bacteria, including strains resistant to other cephalosporins and aminoglycosides.

Pharmacokinetics:

• Absorption: Administered intravenously (IV) or intramuscularly (IM). Bioavailability after IM administration is high (over 90%).
• Distribution: Widely distributed in body fluids and tissues, achieving therapeutic concentrations in most sites of infection. Low serum protein binding.
• Metabolism: Minimal hepatic metabolism. Primarily excreted unchanged.
• Elimination: Primarily via renal excretion (80-90%). Elimination half-life is approximately 2 hours in patients with normal renal function. Hemodialysis removes about 30% of a 1g dose.

Mode of Action (Cellular/Molecular Level): Cefpirome binds to PBPs located on the inner bacterial cell membrane. Different bacterial species have different PBPs, contributing to variations in Cefpirome’s spectrum of activity. Its binding to PBPs halts the transpeptidation reaction, preventing the formation of the peptidoglycan cross-links essential for cell wall integrity.

Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Primarily inhibits PBPs (enzymes). There is no significant interaction with receptors or neurotransmitters.

Elimination Pathways: Predominantly renal excretion of unchanged drug. Minor hepatic metabolism might occur, but it’s not a primary route of elimination.

Dosage

Standard Dosage

Adults:

• IV: 1-2g every 12 hours. Administer IV bolus over 3-5 minutes or IV infusion over 20-30 minutes.
• IM: Similar dosage as IV.

Children:

• IV/IM: 50 mg/kg every 8-12 hours.
• Pediatric Safety Considerations: Limited data available. Use with caution in neonates and infants. Monitor renal function.

Special Cases:

• Elderly Patients: Adjust dose based on renal function. Start with lower doses (e.g., 0.5g).
• Patients with Renal Impairment: Reduce dose based on creatinine clearance (CrCl).
  • CrCl < 50 ml/min: Adjust dosage as per clinical guidelines (Various sources list different dosage adjustments from no change to 50% reduction). See section Dosage Adjustments below.
• Patients with Hepatic Dysfunction: No dose adjustment usually necessary.
• Patients with Comorbid Conditions: Evaluate for potential drug interactions.

Clinical Use Cases

• Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use: 2g every 12 hours or as per clinical guidelines, adjusting for renal function.
• Emergency Situations: 2g every 12 hours. Higher doses might be considered in life-threatening situations.

Dosage Adjustments

• Renal Dysfunction: Dose adjustment crucial. See special cases section above.
• Hepatic Dysfunction: Generally, no adjustment is needed.
• Other factors: Consider other factors, such as age, weight, concomitant medications, and the severity of the infection, when adjusting dosage. See Standard Dosage section above.

Side Effects

Common Side Effects

• Nausea, vomiting, diarrhea
• Rash, itching
• Headache
• Pain at injection site
• Increase in liver enzymes (transient)

Rare but Serious Side Effects

• Allergic reactions (including anaphylaxis)
• Pseudomembranous colitis
• Neutropenia, thrombocytopenia
• Seizures (rare)

Long-Term Effects

• Potential for Clostridium difficile associated diarrhea with prolonged use.
• Secondary infections due to alteration of normal flora.

Adverse Drug Reactions (ADR)

• Anaphylaxis, Stevens-Johnson syndrome (rare).
• Acute kidney injury (rare).

Contraindications

• Hypersensitivity to cefpirome or other cephalosporins.
• History of severe allergic reactions to beta-lactam antibiotics (penicillins).

Drug Interactions

• Aminoglycosides: Increased risk of nephrotoxicity.
• Loop Diuretics: Increased risk of nephrotoxicity.
• Probenecid: Reduces renal clearance of cefpirome, increasing serum levels.
• Anticoagulants: Potential for increased bleeding risk (monitor INR).
• Typhoid and cholera vaccines: May reduce vaccine effectiveness.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Not established. Use with caution, especially in the first trimester. Animal studies do not show teratogenicity.
• Breastfeeding: Cefpirome is excreted in breast milk. Discontinue breastfeeding or the drug.

Drug Profile Summary

• Mechanism of Action: Inhibits bacterial cell wall synthesis by binding to PBPs.
• Side Effects: Nausea, vomiting, diarrhea, rash, headache, injection site pain; rarely, severe allergic reactions, seizures.
• Contraindications: Hypersensitivity to cefpirome or cephalosporins.
• Drug Interactions: Aminoglycosides, loop diuretics, probenecid, anticoagulants.
• Pregnancy & Breastfeeding: Use with caution in pregnancy; discontinue breastfeeding while taking the drug.
• Dosage: 1-2g every 12 hours (IV/IM). Adjust for renal impairment.
• Monitoring Parameters: Renal function, liver enzymes, complete blood count, signs of allergic reactions.

Popular Combinations

Cefpirome is often used alone. In certain cases, it might be combined with other antibiotics (e.g., aminoglycosides) for synergistic effects against resistant organisms, but with careful monitoring for nephrotoxicity. Combination with Sulbactam enhances its efficacy against beta-lactamase producing bacteria.

Precautions

• General Precautions: Monitor renal function, especially in patients with pre-existing renal impairment. Evaluate for drug allergies and history of reactions to beta-lactams.
• Specific Populations: Use cautiously in pregnant/breastfeeding women, elderly, and those with renal or liver disease. No specific precaution in menstruating individuals.
• Lifestyle Considerations: Alcohol interaction is unknown. No specific considerations for smoking or diet. No restriction on driving unless dizziness or other side effects occur.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Cefpirome?

A: The standard adult dose is 1-2g IV/IM every 12 hours. Pediatric dosage is 50 mg/kg IV/IM every 8-12 hours. Adjust the dosage in patients with renal impairment.

Q2: What are the most common side effects?

A: Nausea, vomiting, diarrhea, rash, itching, headache, and pain at the injection site are common side effects.

Q3: Is Cefpirome safe in pregnancy?

A: The safety of cefpirome in pregnancy hasn’t been fully established. Use with caution, especially in the first trimester, and only if clearly needed.

Q4: Can Cefpirome be used in patients with renal impairment?

A: Yes, but the dosage must be reduced based on creatinine clearance. Strict monitoring of renal function is essential.

Q5: What are the serious adverse effects to watch for?

A: Severe allergic reactions (anaphylaxis), Clostridium difficile associated diarrhea (pseudomembranous colitis), neutropenia, and seizures (rare) are serious side effects.

Q6: How is Cefpirome administered?

A: It is administered either intravenously (IV) or intramuscularly (IM).

Q7: What is the mechanism of action of Cefpirome?

A: Cefpirome inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs).

Q8: What drugs should be avoided while taking Cefpirome?

A: Avoid co-administration with aminoglycosides and loop diuretics due to increased risk of nephrotoxicity. Use caution with probenecid and anticoagulants.

Q9: Can Cefpirome be used in children?

A: Yes, the pediatric dose is 50 mg/kg every 8-12 hours. However, data in neonates and infants are limited, so use with caution and monitor renal function.

Q10: What should I monitor in patients receiving Cefpirome?

A: Monitor renal function (serum creatinine, creatinine clearance), liver enzymes, complete blood count, and observe for any signs of allergic reactions. Monitor for signs and symptoms of superinfection (e.g., oral thrush, vaginal yeast infection).