Which of the following is the primary mechanism of antibiotic resistance in Pseudomonas aeruginosa that confers resistance to β-lactam antibiotics?

Explanation

## Antibiotic Resistance Mechanisms in P. aeruginosa **Key Point:** Pseudomonas aeruginosa possesses multiple intrinsic resistance mechanisms, but **AmpC β-lactamase** is the primary enzymatic mechanism conferring resistance specifically to β-lactam antibiotics. ### Primary Mechanism: AmpC β-Lactamase P. aeruginosa harbors a chromosomally encoded, inducible **AmpC β-lactamase** (a class C cephalosporinase) that hydrolyzes the β-lactam ring, directly inactivating β-lactam antibiotics. This is the most clinically recognized primary mechanism of β-lactam resistance in P. aeruginosa: - **Inducible expression**: Exposure to β-lactams (especially cephalosporins and carbapenems) induces AmpC production via the AmpR regulatory system - **Broad substrate range**: Hydrolyzes penicillins, cephalosporins, and monobactams (aztreonam) - **Stable derepression**: Mutations in ampD lead to constitutive high-level AmpC expression, causing clinical treatment failure - **Not inhibited** by classic β-lactamase inhibitors (clavulanate, sulbactam) ### Why Not the Other Options? | Mechanism | Role in β-Lactam Resistance | Notes | |-----------|----------------------------|-------| | **AmpC β-lactamase** ✓ | **Primary** — directly destroys β-lactams | Chromosomally encoded, inducible | | MexAB-OprM efflux pump | Contributes to intrinsic resistance | Broader spectrum (fluoroquinolones, tetracyclines too); not β-lactam-specific | | Altered PBPs | Rare in P. aeruginosa | Major mechanism in MRSA, not Pseudomonas | | Aminoglycoside-modifying enzymes | Irrelevant to β-lactams | Targets aminoglycosides only | **High-Yield:** While MexAB-OprM is constitutively expressed and contributes to intrinsic resistance, it is not β-lactam-specific. AmpC β-lactamase is the **primary mechanism specifically conferring β-lactam resistance** in P. aeruginosa, as it directly inactivates the drug through enzymatic hydrolysis. **Clinical Pearl:** In clinical settings, derepressed AmpC mutants emerge during β-lactam therapy (especially with 3rd-generation cephalosporins), leading to treatment failure — a key reason why P. aeruginosa infections require combination therapy or carbapenems with close monitoring. [cite: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 9th ed.; Murray's Medical Microbiology, 8th ed.]