Antimicrobials · Penicillinase-resistant Penicillins
The facts most likely to be tested
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Nafcillin is the drug of choice for methicillin-susceptible Staphylococcus aureus (MSSA) infections.
The mechanism of action involves binding to penicillin-binding proteins (PBPs) to inhibit bacterial cell wall synthesis.
Nafcillin is specifically indicated for MSSA bacteremia, endocarditis, and osteomyelitis.
Nafcillin is not effective against methicillin-resistant Staphylococcus aureus (MRSA) due to altered PBP2a binding sites.
A major adverse effect of nafcillin is acute interstitial nephritis (AIN), characterized by fever, rash, and eosinophiluria.
Nafcillin is primarily eliminated via the biliary route, requiring no dose adjustment in patients with renal failure.
Nafcillin is a vesicant that can cause severe tissue necrosis if extravasation occurs during intravenous administration.
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A 45-year-old male is hospitalized for persistent fever and back pain following a recent dental procedure. Blood cultures grow Gram-positive cocci in clusters that are confirmed to be methicillin-susceptible Staphylococcus aureus (MSSA). The patient has no known drug allergies. He is started on an intravenous antibiotic, but three days later, he develops a maculopapular rash, fever, and elevated serum creatinine. Urinalysis reveals white blood cell casts and eosinophiluria.
Which of the following is the most likely cause of the patient's current clinical findings?
Acute interstitial nephritis (AIN) secondary to nafcillin
The patient was treated with nafcillin for MSSA, and the development of rash, fever, and eosinophiluria is a classic presentation of drug-induced AIN, a known side effect of penicillin-class antibiotics.
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High yield triage
Classification
Penicillinase-resistant beta-lactam antibiotic.
Indications
Methicillin-susceptible Staphylococcus aureus (MSSA) infections.
Mechanism of Action
Binds penicillin-binding proteins (PBPs) to inhibit bacterial cell wall synthesis.
Side Effects
Rash, phlebitis at IV site, interstitial nephritis.
Contraindications / Monitoring
History of anaphylaxis to penicillins. Monitor serum creatinine and LFTs.
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Mechanism of Action
Nafcillin binds to penicillin-binding proteins (PBPs) located within the bacterial cell wall. This binding inhibits the final stage of peptidoglycan synthesis via transpeptidation. The bulky side chain provides steric hindrance, preventing hydrolysis by staphylococcal beta-lactamases. This renders it effective against organisms that produce penicillinase.
Unique Properties
Unlike other penicillins, nafcillin is primarily eliminated via the biliary route, requiring no dose adjustment in renal failure. It is the drug of choice for MSSA infections due to superior bactericidal activity compared to vancomycin. It is strictly administered via the intravenous route.
Indications
Indicated for serious MSSA infections including endocarditis, osteomyelitis, and bacteremia. It is also the preferred treatment for skin and soft tissue infections caused by susceptible staphylococci. It is ineffective against MRSA due to altered PBP2a binding sites.
Pharmacokinetics
Nafcillin exhibits high protein binding and is metabolized primarily by the liver. Because it is hepatically cleared, it is the preferred antistaphylococcal penicillin in patients with renal impairment. It does not require dosage adjustment for decreased glomerular filtration rates.
Side Effects & Adverse Events
Common adverse effects include hypersensitivity reactions such as urticaria and phlebitis at the infusion site. Acute interstitial nephritis is a classic, serious immune-mediated reaction characterized by fever, rash, and eosinophiluria. Hepatotoxicity may occur with prolonged high-dose therapy.
Contraindications
Absolute contraindication is a history of IgE-mediated hypersensitivity (anaphylaxis, angioedema) to any penicillin. Cross-reactivity with cephalosporins is low but must be considered in patients with severe Type I hypersensitivity reactions.
Monitoring
Monitor serum creatinine and urinalysis to detect early signs of interstitial nephritis. Periodic liver function tests are recommended during extended courses. Assess for signs of phlebitis at the IV site daily.
Clinical Pearls
Always distinguish between MSSA and MRSA; nafcillin is the gold standard for MSSA but is completely inactive against MRSA. If a patient develops a rash and elevated creatinine, suspect interstitial nephritis rather than a simple drug allergy.