Which penicillin is penicillinase-resistant?

• A. Amoxicillin
• B. Benzylpenicillin
• C. Ampicillin
• D. Cloxacillin

Answer: (D)

Penicillinase resistance comes from having bulky side chains around the beta-lactam ring, which protect the core from being hydrolyzed by beta-lactamase enzymes produced by bacteria like Staphylococcus aureus. This design makes the antibiotic effective against penicillinase-producing strains. Among the options, the one with the bulky side chain that imparts this protection is cloxacillin, so it remains active where other penicillins would be degraded by penicillinase. The others—amoxicillin, ampicillin, and benzylpenicillin—lack that bulky shielding and are susceptible to hydrolysis by penicillinase. So this antibiotic is the penicillinase-resistant choice, though it’s mainly useful against penicillinase-producing staphylococci and not broad-spectrum Gram-negative coverage.