Antimicrobial therapy — Which of the following antibiotics cannot be used to treat infections caused by β-lactamase–producing Staphylococcus aureus (consider intrinsic stability and presence or absence of β-lactamase inhibitors)?

Introduction / Context:
β-lactamase–producing Staphylococcus aureus inactivates many β-lactam antibiotics by hydrolyzing their β-lactam ring. This question tests recognition of agents that remain effective versus those predictably inactivated, guiding rational therapy choices for staphylococcal infections.

Given Data / Assumptions:

• Causative organism: β-lactamase–producing Staphylococcus aureus.
• Candidates include a glycopeptide (vancomycin), a β-lactam/β-lactamase inhibitor (ampicillin/sulbactam), a first-generation cephalosporin (cephalothin), and an antipseudomonal penicillin (piperacillin, commonly paired with a β-lactamase inhibitor in practice).
• Goal: identify the agent that cannot be used because it is readily destroyed by staphylococcal β-lactamase.

Concept / Approach:
Drugs with inherent resistance to staphylococcal β-lactamase (e.g., isoxazolyl penicillins) or drugs that are not β-lactams (e.g., vancomycin) retain activity. Adding a β-lactamase inhibitor protects susceptible β-lactams. Early cephalosporins like cephalothin are hydrolyzed by staphylococcal β-lactamases and thus unreliable.

Step-by-Step Solution:

Verification / Alternative check:
Empiric and definitive therapy guidelines for methicillin-susceptible S. aureus favor β-lactamase–stable agents (e.g., nafcillin, oxacillin) or cefazolin rather than cephalothin; for β-lactamase production more broadly, non-β-lactams like vancomycin remain effective when indicated.

Why Other Options Are Wrong:

• Vancomycin: not a β-lactam; unaffected by β-lactamase.
• Ampicillin/sulbactam: inhibitor protects ampicillin from enzyme hydrolysis.
• Piperacillin: clinical use is with tazobactam; inhibitor confers protection.

Common Pitfalls:
Assuming all cephalosporins uniformly resist β-lactamases; in reality, susceptibility varies by generation and enzyme spectrum.

Final Answer:
Cephalothin