Official websites use. Share sensitive information only on official, secure websites. This is an open access article published under a Creative Commons Attribution CC-BY License , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. Bactericidal activity comparable to ciprofloxacin is demonstrated against clinically relevant E.
This paves the way for selective targeting of drug-resistant pathogens without disrupting or selecting for resistance within the microbiota, reducing the rate of secondary infections and subsequent antibiotic use. Antimicrobial drug resistance is a global health emergency, threatening advances in many areas of medicine including surgery, cancer chemotherapy, organ transplantation, and survival of preterm infants. Urinary tract infections UTIs are the most prevalent type of bacterial infection globally.
These infections have a high rate of recurrence and can also lead to serious invasive infections such as sepsis, particularly in the elderly. An additional complication associated with some second-line therapeutics such as ciprofloxacin is host toxicity. Ciprofloxacin holds two black box warnings, one for increased risk of tendinitis and tendon rupture and one for exacerbation of muscle weakness in myasthenia gravis sufferers.
FQAD describes a range of disabling and potentially permanent side effects including disturbances of tendons, joints, muscles, nerves, the nervous system, and induction of type 2 diabetes. Given the drawbacks associated with broad-spectrum antibiotics, efforts have been made to limit their use. Derivatization of the carboxylic acid group of fluoroquinolone antibiotics is associated with a significant decrease in antibacterial activity due to a decreased ability to bind to bacterial DNA—enzyme complexes.
Initial optimization was performed on the cephalosporin portion of the prodrug to enable the rapid generation of analogues and evaluation of biological activity. The cephalosporin analogues with the most desirable activity profile were then selected for preparation as the full prodrug.
