Cefoxitin - Drug Monograph

Introduction

Cefoxitin is a second-generation cephalosporin antibiotic belonging to the cephamycin class, distinguished by its methoxy group at position 7 of the beta-lactam ring. This structural modification enhances its stability against beta-lactamases, particularly those produced by anaerobic bacteria. First approved by the FDA in the 1970s, cefoxitin remains clinically relevant for its broad-spectrum activity against both gram-positive and gram-negative organisms, with particular utility in surgical prophylaxis and treatment of mixed aerobic-anaerobic infections.

Mechanism of Action

Cefoxitin exerts its bactericidal effect through inhibition of bacterial cell wall synthesis. Like other beta-lactam antibiotics, it binds to penicillin-binding proteins (PBPs) located in the bacterial cell wall, particularly PBP-1 and PBP-3. This binding disrupts the transpeptidation process essential for peptidoglycan cross-linking, leading to defective cell wall formation, osmotic instability, and ultimately bacterial cell lysis. The methoxy group at position 7 provides enhanced resistance to degradation by many beta-lactamase enzymes, particularly those produced by Bacteroides fragilis and other anaerobes.

Indications

Cefoxitin is FDA-approved for:

• Treatment of infections caused by susceptible strains of designated microorganisms:

- Lower respiratory tract infections - Urinary tract infections - Intra-abdominal infections - Gynecological infections - Septicemia - Bone and joint infections - Skin and skin structure infections

• Perioperative prophylaxis to reduce incidence of postoperative infections in:

- Colorectal surgery - Vaginal or abdominal hysterectomy - Cesarean section (after umbilical cord clamping)

Common off-label uses include treatment of diabetic foot infections and pelvic inflammatory disease (as part of combination therapy).

Dosage and Administration

• Moderate infections: 1-2 g every 6-8 hours
• Severe infections: 2 g every 4 hours or 3 g every 6 hours
• Maximum daily dose: 12 g

• Colorectal surgery: 2 g IV within 60 minutes before incision, then 2 g every 6 hours for 24 hours
• Hysterectomy: 2 g IV within 60 minutes before incision, then 2 g every 6 hours for 24 hours
• Cesarean section: 2 g IV after umbilical cord clamping, then 2 g every 6 hours for 24 hours

• CrCl 30-50 mL/min: Maximum 2 g every 8-12 hours
• CrCl 10-29 mL/min: Maximum 2 g every 12-24 hours
• CrCl <10 mL/min: Maximum 0.5-1 g every 24-48 hours
• Hemodialysis: Supplemental dose after dialysis

• IV route only (IM administration no longer recommended)
• Infuse over 30-60 minutes
• Reconstitute with Sterile Water for Injection, 0.9% Sodium Chloride, or 5% Dextrose

Pharmacokinetics

Contraindications

• Known hypersensitivity to cefoxitin, other cephalosporins, or any component of the formulation
• History of anaphylactic reactions to penicillins (cross-reactivity risk approximately 1-10%)

Warnings and Precautions

• Hypersensitivity reactions: Cross-reactivity possible in penicillin-allergic patients
• Clostridium difficile-associated diarrhea: May range from mild to life-threatening colitis
• Seizures: Reported with beta-lactam antibiotics, especially in renal impairment
• Nephrotoxicity: Use with caution with other nephrotoxic drugs
• Hemolytic anemia: Has been reported with cephalosporins
• Prothrombin time延长: May occur; monitor patients at risk
• Superinfection: Possible emergence of resistant organisms
• Renal impairment: Dosage adjustment required
• False positive urine glucose: With copper reduction tests (Clinitest); use glucose oxidase methods instead

Drug Interactions

• Probenecid: Decreases renal tubular secretion of cefoxitin, increasing serum concentrations
• Aminoglycosides: Potential additive nephrotoxicity; monitor renal function
• Loop diuretics: Potential additive nephrotoxicity
• Oral anticoagulants: May enhance anticoagulant effect; monitor PT/INR
• Chloramphenicol: Antagonistic antibacterial effect in vitro

Adverse Effects

• Injection site reactions (pain, phlebitis)
• Diarrhea (3-7%)
• Nausea/vomiting (1-2%)
• Eosinophilia (2%)
• Elevated liver enzymes (1-2%)

• Hypersensitivity reactions (anaphylaxis, rash, fever)
• Pseudomembranous colitis
• Hematologic effects (neutropenia, thrombocytopenia, hemolytic anemia)
• Renal dysfunction
• Seizures (especially with high doses in renal impairment)
• Positive direct Coombs test

Monitoring Parameters

• Clinical response to therapy (fever, WBC, symptoms)
• Renal function (serum creatinine, BUN) at baseline and periodically
• CBC with differential weekly during prolonged therapy
• Liver function tests periodically
• Signs of hypersensitivity reactions
• Signs of superinfection or C. difficile-associated diarrhea
• Prothrombin time in patients at risk for hypoprothrombinemia
• Seizure activity in patients with renal impairment receiving high doses

Patient Education

• Complete full course of therapy even if feeling better
• Report any signs of allergic reaction (rash, itching, swelling)
• Report severe diarrhea, especially if bloody or containing mucus
• Inform all healthcare providers of cefoxitin use
• Notify provider if pregnant, planning pregnancy, or breastfeeding
• Be aware that false positive urine glucose tests may occur
• Report unusual bleeding or bruising
• Notify provider of any history of kidney disease

References

1. Lexicomp Online. Cefoxitin: Drug Information. Wolters Kluwer Clinical Drug Information, Inc. 2023. 2. Micromedex Solutions. Cefoxitin. IBM Watson Health. 2023. 3. Gilbert DN, Chambers HF, et al. The Sanford Guide to Antimicrobial Therapy. 52nd ed. 2022. 4. Cefoxitin sodium injection [package insert]. Lake Forest, IL: Hospira, Inc.; 2021. 5. Owens RC Jr, Ambrose PG. Antimicrobial safety: focus on fluoroquinolones. Clin Infect Dis. 2005;41 Suppl 2:S144-S157. 6. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 9th ed. Elsevier; 2020. 7. American Society of Health-System Pharmacists. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2023.