Ceftizoxime

Usage

Ceftizoxime is a third-generation cephalosporin antibiotic indicated for treating various bacterial infections. These include respiratory tract infections (like pneumonia), urinary tract infections, intra-abdominal infections (like peritonitis), septicemia, skin and soft tissue infections, bone and joint infections, and pelvic inflammatory disease. It is also used for surgical prophylaxis and the treatment of uncomplicated gonorrhea. Its pharmacological classification is antibiotic.

Ceftizoxime’s mechanism of action involves inhibiting bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). This binding disrupts the cross-linking of peptidoglycans, essential components of the bacterial cell wall, leading to cell lysis and bacterial death.

Alternate Names

Ceftizoxime is also known internationally and may have regional variations. A popular brand name under which it was previously marketed (discontinued in the US in 2006) is Cefizox.

How It Works

Pharmacodynamics: Ceftizoxime exerts its bactericidal effect by disrupting bacterial cell wall synthesis. It exhibits time-dependent killing, meaning its efficacy is related to the duration of time the drug concentration remains above the minimum inhibitory concentration (MIC) for the target bacteria.

Pharmacokinetics:

• Absorption: Ceftizoxime is administered intravenously (IV) or intramuscularly (IM). It is not available in oral form. After IM administration, it is rapidly absorbed.

• Distribution: It is widely distributed throughout the body, including tissues and fluids, reaching therapeutic concentrations in various organs.

• Metabolism: Ceftizoxime is not extensively metabolized.

• Elimination: It is primarily eliminated by renal excretion, with a half-life of approximately 1.8 hours. Dosage adjustments are necessary in patients with renal impairment.

Mode of Action: Ceftizoxime’s mode of action involves binding to and inhibiting PBPs, specifically PBP3, which is crucial for bacterial cell wall synthesis. This inhibition weakens the cell wall, ultimately causing bacterial cell lysis and death.

Dosage

Standard Dosage

Adults:

The usual adult dosage is 1 to 2 g every 8 to 12 hours IV or IM. For severe or life-threatening infections, doses up to 4g every 8 hours (12 g/day maximum) may be used. For uncomplicated gonorrhea, a single 1 g IM dose is typically administered.

Children:

For children older than 6 months, the recommended dose is 50 mg/kg every 6 to 8 hours IV or IM. The maximum daily dose should not exceed the adult dose. For neonates and infants younger than 6 months, dosing recommendations may vary, and consulting specific pediatric guidelines is crucial.

Special Cases:

• Elderly Patients: Monitor renal function and adjust dosage as needed.

• Patients with Renal Impairment: Dosage adjustments are necessary based on creatinine clearance (CrCl).

• Patients with Hepatic Dysfunction: No dosage adjustment is typically required.

Clinical Use Cases

• Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use: Dosing is generally consistent with the standard adult or pediatric recommendations, adjusted based on the severity of infection. Perioperative prophylaxis often involves a 1.5 g IV dose at the induction of anesthesia, potentially followed by IM doses.

• Emergency Situations: Higher doses (up to 2 g every 4 hours) may be necessary for life-threatening infections.

Dosage Adjustments

Renal impairment necessitates dosage modification. Consult specific guidelines for detailed dosage adjustments based on CrCl.

Side Effects

Common Side Effects:

• Pain, tenderness, and inflammation at the injection site
• Diarrhea
• Nausea and vomiting
• Rash
• Transient elevation in liver enzymes (AST, ALT)

Rare but Serious Side Effects:

• Allergic reactions (including anaphylaxis)
• Seizures (especially in patients with renal impairment)
• Clostridium difficile colitis
• Neutropenia

Adverse Drug Reactions (ADR):

• Severe hypersensitivity reactions (e.g., anaphylaxis) require immediate medical attention.
• Signs of nephrotoxicity or hepatotoxicity necessitate discontinuation of the drug and appropriate management.

Contraindications

• Known hypersensitivity to ceftizoxime or other cephalosporins.
• History of severe allergic reaction to any beta-lactam antibiotic (penicillins, carbapenems, monobactams).

Drug Interactions

• Probenecid can increase serum ceftizoxime levels.
• Aminoglycosides and loop diuretics, when co-administered with high doses of ceftizoxime, may increase the risk of nephrotoxicity.
• Ceftizoxime may decrease the effectiveness of live bacterial vaccines.

Pregnancy and Breastfeeding

Ceftizoxime is classified as Pregnancy Category B. Limited human data suggests low risk, but it should be used during pregnancy only if clearly needed. Ceftizoxime is excreted in breast milk in low concentrations. While adverse effects in breastfed infants are unlikely, monitor for diarrhea or thrush.

Drug Profile Summary

• Mechanism of Action: Inhibits bacterial cell wall synthesis by binding to PBPs.

• Side Effects: Common: injection site reactions, diarrhea, nausea, rash, elevated liver enzymes. Serious: allergic reactions, seizures, C. difficile colitis, neutropenia.

• Contraindications: Hypersensitivity to ceftizoxime or other cephalosporins, severe allergy to beta-lactam antibiotics.

• Drug Interactions: Probenecid, aminoglycosides, loop diuretics, live vaccines.

• Pregnancy & Breastfeeding: Category B, generally considered safe; monitor breastfed infants for GI upset.

• Dosage: Adults: 1–2 g q8–12h IV/IM (up to 12g/day); Children: 50 mg/kg q6–8h IV/IM. Adjustments needed for renal impairment.

• Monitoring Parameters: Renal function (BUN, creatinine), liver function (AST, ALT), signs of infection, complete blood count (CBC).

Precautions

• Assess for allergies to beta-lactams before administration.
• Monitor renal function, especially in patients receiving high doses, the elderly, or those with pre-existing renal impairment.
• Caution in patients with a history of gastrointestinal disease, particularly colitis.

FAQs

Q1: What is the recommended dosage for Ceftizoxime?

A: Adults: 1-2 g IV/IM every 8-12 hours, up to 4 g every 8 hours for severe infections. Children: 50 mg/kg IV/IM every 6-8 hours. Adjust for renal impairment.

Q2: What infections is Ceftizoxime used to treat?

A: Respiratory tract infections, urinary tract infections, intra-abdominal infections, septicemia, skin/soft tissue infections, bone/joint infections, pelvic inflammatory disease, surgical prophylaxis, and gonorrhea.

Q3: How is Ceftizoxime administered?

A: Intravenously (IV) or intramuscularly (IM). No oral formulation is available.

Q4: What are the common side effects of Ceftizoxime?

A: Injection site reactions, diarrhea, nausea/vomiting, rash, and transient increases in liver enzymes.

Q5: What are the serious side effects of Ceftizoxime?

A: Allergic reactions (including anaphylaxis), seizures, Clostridium difficile colitis, and neutropenia.

Q6: Are there any contraindications to Ceftizoxime use?

A: Hypersensitivity to ceftizoxime or other cephalosporins, history of severe reaction to beta-lactam antibiotics.

Q7: Does Ceftizoxime interact with other medications?

A: Yes, it can interact with probenecid, aminoglycosides, loop diuretics, and live vaccines.

Q8: Can Ceftizoxime be used during pregnancy or breastfeeding?

A: It’s a Pregnancy Category B drug, generally considered safe if clearly needed. Monitor breastfed infants for GI disturbances.

Q9: What is the mechanism of action of Ceftizoxime?

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

Q10: What monitoring parameters are important when using Ceftizoxime?

A: Monitor renal function (BUN, creatinine), liver enzymes (AST, ALT), signs of infection resolution, and complete blood counts.