A 68-year-old man with recurrent urinary tract infections is treated with levofloxacin. A resistant strain of Pseudomonas aeruginosa grows in a blood culture. What is the best explanation for this resistance?

Resistance of Pseudomonas aeruginosa to levofloxacin can primarily be attributed to alterations in the bacterial DNA gyrase (a type of topoisomerase). Levofloxacin is a fluoroquinolone antibiotic that targets DNA gyrase and topoisomerase IV, both of which are crucial enzymes for DNA replication and transcription in bacteria. In susceptible strains, levofloxacin effectively binds to and inhibits these enzymes, leading to the disruption of DNA synthesis and ultimately bacterial death.

However, in resistant strains like the one isolated from the blood culture, there may be mutations in the genes encoding these topoisomerases. This can result in changes to the target site of the drug, reducing the affinity of levofloxacin for the enzyme and allowing the bacteria to survive in the presence of the antibiotic. Additionally, Pseudomonas aeruginosa is known for its ability to acquire various resistance mechanisms, including efflux pumps that expel the drug and alterations in membrane permeability that further prevent effective drug concentration within the bacterial cell.

Thus, the development of resistance in this context is best explained by mutations or other mechanisms affecting the topoisomerases, specifically DNA gyrase, making it less susceptible to the action of levof