Cefuroxime - Drug Monograph

Introduction

Cefuroxime is a second-generation cephalosporin antibiotic with broad-spectrum activity against both gram-positive and gram-negative bacteria. It was developed as a semi-synthetic antibiotic derived from cephalosporin C and has been widely used in clinical practice since its approval in the late 1970s. Cefuroxime is available in both oral (cefuroxime axetil) and parenteral (cefuroxime sodium) formulations, making it versatile for various clinical settings from outpatient management to hospital-based care.

Mechanism of Action

Cefuroxime exerts its bactericidal effects by inhibiting bacterial cell wall synthesis through binding to penicillin-binding proteins (PBPs). This interaction disrupts the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, leading to cell lysis and death. Like other β-lactam antibiotics, cefuroxime's activity is time-dependent, requiring concentrations to remain above the minimum inhibitory concentration (MIC) for extended periods during the dosing interval.

The drug demonstrates enhanced stability against many β-lactamases compared to first-generation cephalosporins, particularly against TEM-type β-lactamases produced by Haemophilus influenzae and Neisseria gonorrhoeae. However, it remains susceptible to hydrolysis by extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases.

Indications

Cefuroxime is FDA-approved for:

• Lower respiratory tract infections (including pneumonia and bronchitis)
• Upper respiratory tract infections (pharyngitis, tonsillitis)
• Skin and skin structure infections
• Urinary tract infections
• Uncomplicated gonorrhea
• Early Lyme disease
• Surgical prophylaxis

Off-label uses include:

• Treatment of susceptible bacterial meningitis
• Febrile neutropenia prophylaxis
• Treatment of otitis media and sinusitis

Dosage and Administration

• Adults: 250-500 mg twice daily
• Children: 20-30 mg/kg/day divided twice daily (maximum 1000 mg/day)

• Adults: 750 mg to 1.5 g every 8 hours
• Severe infections: 1.5 g every 6 hours
• Meningitis: 3 g every 8 hours
• Surgical prophylaxis: 1.5 g IV within 60 minutes before incision

• Renal impairment: Dose adjustment required for CrCl <30 mL/min
• Hepatic impairment: No adjustment needed
• Elderly: Consider renal function assessment
• Pregnancy: Category B - generally considered safe
• Lactation: Small amounts excreted in breast milk

Pharmacokinetics

Contraindications

• Known hypersensitivity to cefuroxime or other cephalosporins
• Patients with history of severe hypersensitivity reactions to penicillins (cross-reactivity risk)
• History of cephalosporin-associated hemolytic anemia

Warnings and Precautions

• Cross-sensitivity: Approximately 5-10% of penicillin-allergic patients may experience cross-reactivity
• Clostridium difficile-associated diarrhea: May range from mild to life-threatening colitis
• Hemolytic anemia: Has been reported with cephalosporin use
• Renal impairment: Requires dosage adjustment
• Seizure risk: May occur in patients with renal impairment when doses are not adjusted
• Superinfection: Prolonged use may result in fungal or bacterial superinfection
• False positive urine glucose: May occur with copper reduction tests

Drug Interactions

• Probenecid: Decreases renal clearance of cefuroxime, increasing serum levels
• Oral contraceptives: May reduce efficacy; recommend additional contraception
• Warfarin: May potentiate anticoagulant effect (monitor INR)
• Aminoglycosides: Increased risk of nephrotoxicity
• Loop diuretics: Increased risk of nephrotoxicity
• Alcohol: Disulfiram-like reaction possible (though rare with cephalosporins)

Adverse Effects

• Gastrointestinal: Diarrhea, nausea, vomiting, abdominal pain
• Dermatological: Rash, pruritus
• Hepatic: Transient elevation of liver enzymes
• Hematological: Eosinophilia, thrombocytosis

• Anaphylaxis and severe hypersensitivity reactions
• Pseudomembranous colitis
• Hemolytic anemia
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Interstitial nephritis
• Seizures (especially with renal impairment)

Monitoring Parameters

• Clinical response to therapy
• Signs of hypersensitivity reactions
• Complete blood count with differential
• Renal function tests (BUN, creatinine)
• Liver function tests
• Stool frequency and consistency (for C. difficile)
• Prothrombin time in patients on anticoagulants
• Signs of superinfection

Patient Education

• Complete the full course of therapy even if symptoms improve
• Take oral form with food to enhance absorption
• Report any signs of allergic reaction (rash, itching, swelling)
• Report severe diarrhea, especially if containing blood or mucus
• Inform healthcare providers of all medications being taken
• Oral suspension should be shaken well before use
• Store suspension in refrigerator and discard after 10 days
• Use additional contraception if taking oral contraceptives
• Avoid alcohol during therapy due to potential reaction

References

1. Pfizer Laboratories. Zinacef® (cefuroxime sodium) prescribing information. 2021. 2. GlaxoSmithKline. Ceftin® (cefuroxime axetil) prescribing information. 2020. 3. Bradley JS, Nelson JD. Nelson's Pocket Book of Pediatric Antimicrobial Therapy. 22nd ed. American Academy of Pediatrics; 2021. 4. Gilbert DN, Chambers HF, Saag MS, et al. The Sanford Guide to Antimicrobial Therapy. 52nd ed. Antimicrobial Therapy Inc; 2022. 5. Lexicomp Online. Cefuroxime monograph. Wolters Kluwer Clinical Drug Information. Accessed January 2023. 6. Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing. 32nd ed. CLSI supplement M100; 2022. 7. Mandell GL, Bennett JE, Dolin R. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 9th ed. Elsevier; 2020.