What is the primary cause of resistance to aminoglycosides?

The primary cause of resistance to aminoglycosides is decreased active transport into bacterial cells. Aminoglycosides are known to rely on an oxygen-dependent active transport mechanism to penetrate the bacterial cell membrane. If a bacterium reduces the expression of the transport proteins responsible for this process or alters the permeability of its membrane, the aminoglycoside drugs cannot effectively enter the cells, leading to resistance.

This transport mechanism is particularly important as aminoglycosides are typically ineffective against anaerobic bacteria because oxygen is required for their uptake. Therefore, if a bacterial strain modifies its transport system or adopts mutations that hinder the drug's ability to penetrate, it can evade the effects of aminoglycosides, resulting in resistance.

In terms of the other options, altered target sites primarily contribute to resistance against other antibiotic classes rather than aminoglycosides. Increased metabolism and enhanced drug breakdown involve different mechanisms, such as enzymatic inactivation or modification of the drug itself, but these are not the primary means through which aminoglycoside resistance manifests. Thus, the most critical factor in aminoglycoside resistance is the decrease in active transport into the cells.