Search. Learn. Save

Platform for Pharmaceutical Products for Healthcare Professionals
Search By
☰ Generic Formulas

Generic Formulas X

Cephazolin

Cefazolin: A Comprehensive Overview of the First-Generation Cephalosporin Antibiotic

Cefazolin is a first-generation cephalosporin antibiotic, widely used in clinical settings for its potent bactericidal activity against gram-positive organisms and selected gram-negative bacteria. Known for its relatively long half-life, excellent tissue penetration, and favorable safety profile, Cefazolin continues to play a critical role in both prophylactic and therapeutic interventions in infectious diseases.

Introduction to Cefazolin

Cefazolin (INN, USAN), also known as cephazolin, is a beta-lactam antibiotic that belongs to the cephalosporin family. It was introduced in the early 1970s and quickly gained popularity due to its broad activity against staphylococci and streptococci, combined with its ease of use in surgical prophylaxis. It is administered parenterally (intravenous or intramuscular routes) because of poor oral bioavailability.

Chemical Structure and Properties

Cefazolin’s chemical formula is C14H14N8O4S3, and its structure contains the characteristic β-lactam ring essential for its antibacterial activity. As with all cephalosporins, it is derived from 7-aminocephalosporanic acid. The molecule includes a 1,3-thiazole ring and a tetrazole ring, which contribute to its antimicrobial spectrum and resistance to β-lactamase hydrolysis in certain strains.

Mechanism of Action

Cefazolin acts by inhibiting bacterial cell wall synthesis. Specifically, it binds to penicillin-binding proteins (PBPs) within the bacterial cell membrane. These PBPs are crucial for the final stages of peptidoglycan synthesis, which provides structural integrity to bacterial cell walls. Inhibition of these enzymes results in the weakening of the cell wall, osmotic instability, and ultimately bacterial lysis and death. Cefazolin is bactericidal, meaning it kills bacteria rather than merely inhibiting their growth.

Spectrum of Activity

Cefazolin is most effective against gram-positive cocci and some gram-negative bacilli. Notably, it has:

Strong Activity Against:

  • Staphylococcus aureus (methicillin-sensitive strains, MSSA)

  • Streptococcus pyogenes

  • Streptococcus pneumoniae

  • Streptococcus agalactiae

Moderate Activity Against:

  • Escherichia coli

  • Klebsiella pneumoniae

  • Proteus mirabilis

Limited or No Activity Against:

  • Methicillin-resistant Staphylococcus aureus (MRSA)

  • Pseudomonas aeruginosa

  • Enterococci

  • Anaerobes

  • Bacteroides fragilis

Pharmacokinetics

Cefazolin has several pharmacokinetic properties that make it highly suitable for various clinical uses:

  • Absorption: Not orally bioavailable; given IV or IM.

  • Distribution: Good penetration into most tissues, including bone, skin, and soft tissue.

  • Protein Binding: High (~80-85%)

  • Half-life: 1.5–2 hours (prolonged in renal impairment)

  • Excretion: Primarily renal, unchanged in the urine.

Because of its renal excretion, dosage adjustments are necessary in patients with impaired kidney function.

Clinical Uses

Cefazolin remains a mainstay in multiple therapeutic and prophylactic regimens. Its clinical applications include:

1. Surgical Prophylaxis

Cefazolin is the drug of choice for preoperative antibiotic prophylaxis due to its excellent activity against skin flora, favorable pharmacokinetics, and safety. It is commonly used in:

  • Orthopedic surgeries

  • Cardiothoracic procedures

  • Gastrointestinal surgeries

  • Cesarean sections

2. Skin and Soft Tissue Infections (SSTIs)

Effective against Staphylococcus aureus and Streptococcus pyogenes, Cefazolin is used for cellulitis, abscesses, and wound infections.

3. Bone and Joint Infections

Osteomyelitis and septic arthritis caused by susceptible organisms are often treated with Cefazolin, especially when MSSA is involved.

4. Urinary Tract Infections (UTIs)

Although not first-line for UTIs due to resistance patterns, Cefazolin can be used in inpatient settings for complicated UTIs.

5. Respiratory Tract Infections

Includes community-acquired pneumonia and hospital-acquired infections, when the causative organism is susceptible.

6. Endocarditis

In some cases of native-valve endocarditis due to MSSA or Streptococcus species, Cefazolin is preferred due to its lower toxicity compared to nafcillin.

Dosing Guidelines

Typical adult dosages range from 1 to 2 grams IV every 8 hours, depending on the severity and site of infection. Pediatric doses are calculated based on body weight.

For surgical prophylaxis, a single 1-2 gram IV dose administered within 60 minutes before incision is standard practice.

In patients with renal impairment, dosing adjustments are crucial to avoid accumulation and toxicity.

Side Effects and Adverse Reactions

Cefazolin is generally well tolerated, but side effects can occur:

Common Adverse Effects:

  • Gastrointestinal disturbances (nausea, diarrhea)

  • Injection site reactions

  • Rash or pruritus

Serious Reactions:

  • Hypersensitivity reactions, including anaphylaxis

  • Clostridioides difficile-associated diarrhea (CDAD)

  • Neutropenia or leukopenia with prolonged use

  • Seizures (rare, usually in renal impairment)

Cross-reactivity with penicillin allergies can occur, but true cross-reactivity is relatively low (~1-2%).

Resistance Patterns

Resistance to Cefazolin is on the rise, particularly among gram-negative bacteria. Mechanisms include:

  • Production of beta-lactamases, which hydrolyze Cefazolin’s β-lactam ring.

  • Altered penicillin-binding proteins.

  • Efflux pumps and porin mutations in gram-negatives.

MRSA and certain Enterobacteriaceae with extended-spectrum beta-lactamases (ESBLs) are inherently resistant to Cefazolin.

Comparison with Other Cephalosporins

As a first-generation cephalosporin, Cefazolin differs from later generations in spectrum and pharmacokinetics:

Generation Example Gram-positive Gram-negative Pseudomonas Route
1st Cefazolin ++++ ++ – IV/IM
2nd Cefuroxime +++ +++ – IV/IM/PO
3rd Ceftriaxone ++ ++++ – IV/IM
4th Cefepime ++ +++++ + IV

Cefazolin is preferred for MSSA over ceftriaxone due to better efficacy despite ceftriaxone’s broader spectrum.

Use in Special Populations

Pregnancy:

Cefazolin is classified as Pregnancy Category B. It is considered safe and is commonly used for surgical prophylaxis during Cesarean delivery.

Pediatrics:

Widely used in neonates and children with appropriate dosing adjustments.

Geriatrics:

Effective and safe when renal function is monitored closely.

Role in Antimicrobial Stewardship

Cefazolin is a key agent in antimicrobial stewardship due to:

  • Narrow spectrum (reduces collateral damage to microbiota)

  • Low resistance potential for MSSA and streptococci

  • Effective alternative to broader-spectrum antibiotics

Switching from broad-spectrum agents like vancomycin or ceftriaxone to Cefazolin when cultures show MSSA is a cornerstone of stewardship programs.

Recent Research and Developments

1. Outpatient Parenteral Antimicrobial Therapy (OPAT)

Cefazolin’s relatively long half-life allows once- or twice-daily administration, making it ideal for OPAT programs.

2. Combination Therapies

Studies have investigated the combination of Cefazolin with probenecid to prolong serum levels, as well as combinations with other beta-lactams in polymicrobial infections.

3. Clinical Trials

Recent clinical trials explore its use in early-switch strategies and compare outcomes with other first-line agents in specific infections like MSSA bacteremia.

Conclusion

Cefazolin remains a foundational antibiotic in modern medicine. Its efficacy against gram-positive organisms, particularly MSSA and streptococci, makes it indispensable in hospital settings, especially for surgical prophylaxis and soft tissue infections. While resistance patterns and newer agents continue to influence treatment choices, Cefazolin’s safety, cost-effectiveness, and targeted action ensure its continued relevance. Healthcare providers must remain vigilant about appropriate use, monitor for resistance trends, and incorporate Cefazolin strategically within broader antimicrobial stewardship efforts to maintain its utility for future generations.