Quinolones Antibody (YA903)(PBS only)

Quinolones is a Quinolones are synthetic antimicrobials based on the 4-oxo-1, 4-dihydroquinolone skeleton, developed in the early 1960s; two decades later, fluoroquinolones were designed with a broader antimicrobial spectrum and good oral absorption. The first-generation quinolones, such as nalidixic and oxolinic acids, act against Gram-negative bacteria and are used to treat urinary tract infections. The second-generation quinolones are fluoroquinolones (e.g., enrofloxacin, danofloxacin, ciprofloxacin) containing a fluorine atom at position 6 and a bulky piperidine at position 7, broadening the antimicrobial spectrum to Pseudomonas species and some Gram-positive organisms like Staphylococcus aureus. They are active against aerobic Gram-negative bacilli, particularly enterobacteriaceae, Haemophilus, and pseudomonadaceae, with therapeutic indications including urinary tract infections, prostatitis, gastrointestinal and abdominal infections, as well as prophylaxis and therapy of "traveller’s disease" and other severe gastrointestinal diseases. In livestock, they show high activity against a wide range of diseases; in the EU, seven quinolones (danofloxacin, difloxacin, enrofloxacin, flumequine, marbofloxacin, oxolinic acid, sarafloxacin) are approved for use in food-producing animals, with maximum residue limits (MRLs) in meat matrices varying by drug and tissue. Their mechanism of action involves converting target topoisomerases (gyrase and topoisomerase IV) into toxic enzymes that fragment the bacterial chromosome, or forming reversible drug–enzyme–DNA complexes with these two enzymes, blocking DNA replication and RNA synthesis to inhibit bacterial growth and kill bacteria rapidly, with rapid lethal action proposed to arise from the release of DNA breaks from the complexes. Bacteria acquire resistance to quinolones through mutations and/or altered expression of target proteins (gyrase and topoisomerase IV), drug permeability proteins, drug efflux proteins, and gyrase-protecting proteins, as well as via plasmid-mediated quinolone resistance (PMQR) mechanisms; resistance is acquired spontaneously and through quinolone-mediated induction of the mutagenic SOS response, with selective enrichment of mutants strongly dependent on quinolone concentration, and the mutant prevention concentration (MPC) serving as a measure of antimutant activity. They have a high safety profile with rare serious side effects including QTc elongation, hepatotoxicity, and tendon rupture, and can also perturb mitochondrial functions, which can be reduced by antioxidants. Extensive use in humans and animals has led to the rapid emergence of resistance, with rare and scattered data from Arab countries; understanding the prevalence and distribution of PMQR is essential to stop the irrational use of quinolones in these regions.