Which of the following mechanisms of resistance is MOST commonly seen in gram-negative bacteria that are resistant to aminoglycosides?

Explanation

## Aminoglycoside Resistance Mechanisms **Key Point:** Enzymatic inactivation by aminoglycoside-modifying enzymes (phosphorylases, nucleotidyltransferases, and acetyltransferases) is the MOST common mechanism of resistance in gram-negative bacteria. These enzymes are often plasmid-encoded and can be transferred between organisms. **High-Yield:** Three major classes of aminoglycoside-inactivating enzymes exist: ### Aminoglycoside-Modifying Enzymes | Enzyme Class | Mechanism | Example | | --- | --- | --- | | Phosphorylases (APH) | Phosphorylation of hydroxyl groups | APH(3')-VI, APH(6)-I | | Nucleotidyltransferases (ANT) | Adenylylation of hydroxyl groups | ANT(2'') | | Acetyltransferases (AAC) | Acetylation of amino groups | AAC(6')-I, AAC(3)-I | **Clinical Pearl:** Amikacin and netilmicin are more resistant to enzymatic inactivation than gentamicin and tobramycin because of their structural modifications. This is why amikacin is often used for resistant gram-negative infections. **Mnemonic:** **PAA** — Phosphorylases, Acetyltransferases, Adenylyltransferases (the three major aminoglycoside-inactivating enzyme families). ### Why Other Mechanisms Are Less Common in Gram-Negatives - **Decreased cell wall permeability:** Gram-negative bacteria have outer membranes that are generally permeable to aminoglycosides; this is more relevant in gram-positive organisms. - **Ribosomal methylation:** This is the primary resistance mechanism in gram-positive bacteria (e.g., *Staphylococcus aureus*) and anaerobes, not gram-negatives. - **Efflux pumps:** While present in gram-negatives, they are a minor contributor to aminoglycoside resistance compared to enzymatic inactivation.