Cefazolin

Cefazolin, also known as cefazoline or cephazolin, is a first-generation cephalosporin antibiotic. It is prescribed for bacterial infections including cellulitis, urinary tract infections, pneumonia, endocarditis, joint infections, and biliary tract infections. It is also used to prevent group B streptococcal disease around childbirth and to prevent infections before surgery. The medication is administered via injection into a muscle or vein.

Common side effects include diarrhea, vomiting, yeast infections, and allergic reactions. While it was once thought unsafe for people with penicillin allergies, recent studies show it is safe for nearly all patients, including those with known penicillin allergies. It is generally considered safe during pregnancy and breastfeeding. Cefazolin works by interfering with bacterial cell wall construction.

Cefazolin was patented in 1967 and became commercially available in 1971. It is on the World Health Organization's List of Essential Medicines and is available as a generic medication.

Medical uses

The drug is used for respiratory tract infections, urinary tract infections, skin infections, biliary tract infections, bone and joint infections, genital infections, blood infections (sepsis), and endocarditis, provided the bacteria are susceptible. It is also used peri-operatively to prevent post-surgical infections and is often the preferred drug for surgical prophylaxis. Cefazolin does not penetrate the central nervous system, so it is ineffective against meningitis.

It is effective against methicillin-susceptible Staphylococcus aureus (MSSA) but not against methicillin-resistant Staphylococcus aureus (MRSA). For many staphylococcal infections, such as bacteremia, cefazolin is an alternative for patients allergic to penicillin, though a reaction is still possible. Resistance occurs in bacteria like Mycoplasma and Chlamydia, where other cephalosporins may be more effective. It does not work against Enterococcus, anaerobic bacteria, or atypical bacteria.

Bacterial susceptibility

As a first-generation cephalosporin, cefazolin is highly active against gram-positive bacteria and some gram-negative bacteria, due to its stability against many bacterial beta-lactamases. Susceptible gram-positive aerobes include Staphylococcus aureus (including beta-lactamase-producing strains), Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, and other streptococci. Susceptible gram-negative aerobes include Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae. Non-susceptible organisms include MRSA, Enterococcus, most indole-positive Proteus (e.g., Proteus vulgaris), Enterobacter spp., Morganella morganii, Providencia rettgeri, Serratia spp., Pseudomonas spp., and Listeria.

Pregnancy

In pregnancy, cefazolin is category B and generally safe. A small amount enters breast milk, so caution is advised during breastfeeding. It can be used prophylactically against perinatal group B streptococcal infection; for penicillin-allergic women without a history of anaphylaxis, cefazolin is an alternative, though close monitoring is recommended due to a small risk of allergic reaction. Safety and effectiveness have not been established for premature infants or neonates.

Additional considerations

In elderly patients, clinical trials found no overall differences in safety or effectiveness, though some older individuals may have higher sensitivity. People with kidney disease or on hemodialysis may need dose adjustments; liver disease does not significantly affect cefazolin levels. It may interact with other medications, notably probenecid.

Common side effects (1–10%) include diarrhea, stomach pain or upset, vomiting, and rash. Uncommon side effects (<1%) include dizziness, headache, fatigue, itching, and transient hepatitis. Patients with penicillin allergies may have a reaction.

As with other antibiotics, watery or bloody stools occurring up to three months after therapy should be reported. Cefazolin’s chemical structure contains an N-methylthiodiazole (NMTD) side-chain; when broken down, it releases free NMTD, which can cause hypoprothrombinemia (likely by inhibiting vitamin K epoxide reductase) and a disulfiram-like reaction with ethanol (by inhibiting aldehyde dehydrogenase). Cross-sensitivity may occur in those allergic to penicillin.

Cefazolin inhibits cell wall biosynthesis by binding to penicillin-binding proteins, stopping peptidoglycan synthesis. Penicillin-binding proteins are bacterial proteins that help catalyze this process.