Introduction
Cefixime is a third-generation oral cephalosporin antibiotic with broad-spectrum activity against Gram-negative bacteria while maintaining activity against some Gram-positive organisms. It was first approved by the FDA in 1989 and remains an important therapeutic option for various bacterial infections due to its favorable pharmacokinetic profile and convenient once-daily dosing.
Mechanism of Action
Cefixime exerts its bactericidal effect by inhibiting bacterial cell wall synthesis through binding to penicillin-binding proteins (PBPs). Like other beta-lactam antibiotics, it interferes with the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, leading to cell lysis and death. Its enhanced stability against beta-lactamases, particularly those produced by Gram-negative bacteria, contributes to its expanded spectrum of activity compared to earlier cephalosporins.
Indications
FDA-approved indications include:
- Acute exacerbations of chronic bronchitis
- Acute bacterial otitis media
- Pharyngitis and tonsillitis
- Uncomplicated urinary tract infections
- Uncomplicated gonorrhea (urethral and cervical)
Off-label uses (supported by clinical evidence):
- Typhoid fever
- Shigellosis
- Lyme disease (early stage)
- Prophylaxis in certain surgical procedures
Dosage and Administration
Standard dosing:- Adults: 400 mg once daily or 200 mg every 12 hours
- Children: 8 mg/kg/day (maximum 400 mg daily)
- CrCl 20-60 mL/min: 75% of standard dose
- CrCl <20 mL/min: 50% of standard dose
- Hemodialysis: 300 mg after each dialysis
- Oral administration with or without food
- Suspension should be shaken well before use
- Complete full course of therapy even if symptoms improve
Pharmacokinetics
Absorption: 40-50% oral bioavailability, not significantly affected by food Distribution: Widely distributed to tissues and fluids; CSF penetration poor Protein binding: Approximately 65% Metabolism: Minimal hepatic metabolism Elimination: Primarily renal excretion (50% unchanged); half-life 3-4 hours Special populations: Elimination prolonged in renal impairmentContraindications
- Known hypersensitivity to cefixime or other cephalosporins
- History of severe hypersensitivity reactions to penicillins (cross-reactivity risk)
- Anaphylactic reactions to any beta-lactam antibiotic
Warnings and Precautions
- Clostridium difficile-associated diarrhea: May range from mild to life-threatening
- Cross-sensitivity: Approximately 5-10% of penicillin-allergic patients may react to cephalosporins
- Renal impairment: Dosage adjustment required
- Hemolytic anemia: Has been reported with cephalosporins
- Superinfection: Possible emergence of resistant organisms
- Pseudomembranous colitis: Discontinue if diarrhea develops
Drug Interactions
- Warfarin: May potentiate anticoagulant effect (monitor INR)
- Probenecid: Increases cefixime concentrations
- Oral contraceptives: Potential decreased efficacy (use backup contraception)
- Aminoglycosides: Increased risk of nephrotoxicity
- Chloramphenicol: Antagonistic antibacterial effect
Adverse Effects
Common (>1%):- Diarrhea (16%)
- Nausea (7%)
- Abdominal pain (3%)
- Headache (2%)
- Vaginitis (2%)
- Pseudomembranous colitis
- Stevens-Johnson syndrome
- Anaphylaxis
- Hemolytic anemia
- Hepatotoxicity
- Acute renal failure
- Seizures
Monitoring Parameters
- Clinical response to therapy
- Signs of superinfection
- Renal function (baseline and during prolonged therapy)
- CBC with differential if prolonged therapy
- Stool frequency and consistency
- Signs of hypersensitivity reactions
- INR if co-administered with warfarin
Patient Education
- Complete entire course of therapy as prescribed
- Take at same time each day
- Report severe diarrhea, bloody stools, or abdominal pain
- Inform healthcare provider of any allergy history
- Use alternative contraception if taking oral contraceptives
- Do not share medication with others
- Store suspension refrigerated and discard after 14 days
- Report any signs of allergic reaction (rash, swelling, difficulty breathing)
References
1. FDA Prescribing Information: Suprax (cefixime) 2. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing 3. Gilbert DN, et al. The Sanford Guide to Antimicrobial Therapy 4. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases 5. Micromedex Solutions: Cefixime Drug Information 6. American Society of Health-System Pharmacists. AHFS Drug Information 7. Nelson JD, et al. "Cefixime: A Review of its Antibacterial Activity and Clinical Efficacy" Drugs