What is nafcillin?

Nafcillin: A Semisynthetic Penicillinase-Resistant Penicillin

Nafcillin is a semisynthetic, β-lactamase-resistant penicillin that serves as a first-line treatment for methicillin-susceptible Staphylococcus aureus (MSSA) infections, particularly in serious infections like endocarditis, where it is administered intravenously for 4-6 weeks. 1

Pharmacology and Mechanism of Action

Nafcillin belongs to the penicillin family of antibiotics and is specifically classified as a penicillinase-resistant penicillin. Its chemical structure includes an acyl side chain that prevents disruption of the beta-lactam ring by penicillinase (beta-lactamase) enzymes produced by many staphylococci. 2

Key characteristics:

• Semisynthetic penicillin derived from 6-aminopenicillanic acid
• Resistant to inactivation by penicillinase (beta-lactamase)
• Available for intravenous or intramuscular administration
• Bactericidal activity against susceptible organisms 1

Clinical Indications

Nafcillin is specifically indicated for:

• Infections caused by penicillinase-producing staphylococci that demonstrate susceptibility to the drug
• First-line therapy for methicillin-susceptible S. aureus (MSSA) infections
• Native valve infective endocarditis caused by MSSA 3

Important clinical applications include:

• Methicillin-susceptible S. aureus endocarditis
• Serious MSSA bloodstream infections
• MSSA skin and soft tissue infections
• MSSA osteomyelitis

Treatment Recommendations for Specific Conditions

Infective Endocarditis

• For MSSA native valve endocarditis: Nafcillin or oxacillin given intravenously for a minimum of 4-6 weeks 3
• Standard dosing: 8-12 g/24 hours IV divided into 3-4 doses 4
• The addition of gentamicin for the first 3-5 days is optional and may accelerate killing of staphylococci, but increases risk of nephrotoxicity 3

Prosthetic Valve Endocarditis

• For MSSA prosthetic valve endocarditis: Nafcillin or oxacillin plus rifampin for 6 weeks, with gentamicin added for the first 2 weeks if susceptible 3, 4

Advantages and Limitations

Advantages:

• Superior efficacy against MSSA compared to vancomycin
• Bactericidal activity
• Excellent tissue penetration
• Low toxicity profile compared to some alternatives

Limitations:

• Higher risk of nephrotoxicity compared to cefazolin 5
• Not effective against methicillin-resistant staphylococci (MRSA)
• Requires intravenous administration for serious infections
• Risk of hypersensitivity reactions in penicillin-allergic patients

Important Clinical Considerations

1. Susceptibility Testing: Culture and susceptibility tests should be performed to determine the causative organism and its susceptibility to nafcillin 1

2. MRSA Infections: Nafcillin should not be used for infections caused by methicillin-resistant staphylococci, regardless of in vitro susceptibility results due to cross-resistance 3, 4

3. Alternative Agents:

   • For non-anaphylactic penicillin allergies: Cefazolin is an appropriate alternative 4
   • For severe penicillin allergies: Vancomycin is recommended 4
   • For patients with renal concerns: Cefazolin may be preferred due to lower nephrotoxicity risk 5

4. Brain Abscess: In cases of brain abscess complicating MSSA infection, nafcillin is preferred over cefazolin due to better blood-brain barrier penetration 3

Monitoring and Safety

• Monitor for signs of acute kidney injury, which occurs more frequently with nafcillin than with cefazolin 5
• Watch for hypersensitivity reactions, particularly in patients with penicillin allergy
• Regular assessment of clinical response and microbiological clearance is essential

Nafcillin remains a cornerstone antibiotic for the treatment of serious MSSA infections, with decades of clinical experience supporting its efficacy and safety profile when used appropriately.