Antimicrobials · First-Generation Cephalosporins
The facts most likely to be tested
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Cefazolin is a first-generation cephalosporin that provides excellent coverage against Gram-positive cocci, specifically Staphylococcus aureus and Streptococcus species.
Cefazolin is the prophylactic antibiotic of choice for most clean surgical procedures to prevent surgical site infections.
Cefazolin is the preferred treatment for methicillin-susceptible Staphylococcus aureus (MSSA) infections, including skin and soft tissue infections and bacteremia.
Cefazolin exhibits bactericidal activity by binding to penicillin-binding proteins (PBPs), thereby inhibiting bacterial cell wall synthesis.
Cefazolin does not provide reliable coverage against methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus, or atypical pathogens.
Cefazolin has a unique R1 side chain shared with no penicillin, so cross-reactivity is negligible and current guidelines permit its use for surgical prophylaxis even in patients with a reported penicillin allergy, including prior anaphylaxis; older board sources still teach avoidance.
Cefazolin is primarily excreted via the kidneys, necessitating dosage adjustments in patients with significant renal impairment.
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A 55-year-old male is scheduled for an elective total hip arthroplasty. He has no known drug allergies and a past medical history significant for hypertension. His physical examination is unremarkable, and his preoperative laboratory studies are within normal limits. The surgical team intends to administer prophylactic antibiotics 60 minutes prior to the initial incision. The patient is currently afebrile with stable vital signs.
Which of the following is the most appropriate prophylactic antibiotic for this patient?
Cefazolin
Cefazolin is the gold standard for surgical prophylaxis in clean procedures like orthopedic surgery due to its efficacy against skin flora, specifically MSSA, testing Bet #2.
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Classification
First-generation cephalosporin; beta-lactam antibiotic.
Indications
Surgical prophylaxis and MSSA skin/soft tissue infections.
Mechanism of Action
Inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs).
Side Effects
Hypersensitivity reactions; anaphylaxis; C. difficile-associated diarrhea.
Contraindications / Monitoring
History of severe anaphylaxis to beta-lactams. Monitor renal function.
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Mechanism of Action
Cefazolin binds to penicillin-binding proteins (PBPs) located on the inner bacterial cell membrane. This binding inhibits the final transpeptidation step of peptidoglycan synthesis, leading to cell lysis. It is primarily active against Gram-positive cocci and select Gram-negative rods.
Unique Properties
It is the gold standard for surgical prophylaxis due to its excellent tissue penetration and half-life. Unlike later generations, it lacks significant activity against anaerobes or Pseudomonas.
Indications
It is the first-line agent for surgical prophylaxis to prevent Staphylococcus aureus wound infections. It is also used for cellulitis and impetigo caused by MSSA or Streptococcus pyogenes.
Pharmacokinetics
Excreted primarily via the kidneys through glomerular filtration and tubular secretion. Dosage adjustments are mandatory in patients with renal impairment to prevent accumulation and neurotoxicity.
Side Effects & Adverse Events
Common effects include nausea, vomiting, and diarrhea. Anaphylaxis and angioedema are rare but life-threatening hypersensitivity reactions. Prolonged use may lead to Clostridioides difficile-associated diarrhea.
Contraindications
Absolute contraindication in patients with a history of IgE-mediated reactions (e.g., anaphylaxis, urticaria) to cefazolin or another cephalosporin; because cefazolin's R1 side chain is not shared with any penicillin, penicillin allergy alone is not an absolute contraindication. Use with extreme caution in patients with a history of penicillin allergy due to potential cross-reactivity.
Monitoring
Monitor serum creatinine and BUN to adjust dosing in renal insufficiency. Observe for signs of superinfection or C. difficile colitis if therapy is extended.
Clinical Pearls
On boards, Cefazolin is the answer for pre-operative prophylaxis unless the patient has a severe penicillin allergy. It does not cross the blood-brain barrier effectively and should never be used to treat meningitis.