1. History of Quinolones antibiotics
The founding member of the quinolone drug class, nalidixic acid, is a naphthyridine that was first isolated by George Lesher and colleagues in 1962 as a byproduct of chloroquine synthesis. Nalidixic acid was introduced into the clinic in the 1960s for the treatment of uncomplicated urinary tract infections caused by enteric bacteria. By the 1970s, several first-generation quinolones, oxolinic acid being the most notable, had been synthesized and introduced into the clinic.
The quinolones were a little-used drug class until the early 1980s, when a second generation of compounds was developed. These newer drugs, highlighted by norfloxacin, ciprofloxacin, and ofloxacin, displayed considerably improved activity against gyrase, greater penetration into Gram-positive organisms, and enhanced pharmacokinetics and pharmacodynamics. The most critical changes to the quinolone skeleton were the introduction of a fluorine at position C6 and a major ring substituent (piperazine or methyl-piperazine) at C7. Because of the inclusion of the fluorine, quinolones are often termed "fluoroquinolones".
A number of diseases currently are treated with quinolones, including urinary tract infections and pyelonephritis, sexually transmitted diseases, prostatitis, skin and tissue infections, chronic bronchitis, community-acquired and nosocomial pneumonia, and intra-abdominal and pelvic infections.
2. Classification of beta-lactam antibiotics
The quinolones can be classified into four generations based on antimicrobial activity.
| Quinolone generations | Characteristics | Drugs |
|---|---|---|
|
First generation |
Moderate gram-negative activity and minimal systemic distribution |
Nalidixic acid, Cinoxacin |
|
Second generation |
Expanded gram-negative activity and atypical pathogen coverage, but limited gram-positive activity |
Lomefloxacin, Norfloxacin, Enoxacin, Ofloxacin, Ciprofloxacin |
|
Third generation |
Retain expanded gram-negative and atypical intracellular activity but have improved gram-positive coverage |
Levofloxacin, Sparfloxacin, Gatifloxacin, Moxifloxacin |
|
Fourth generation |
Improve gram-positive coverage, maintain gram-negative coverage, and gain anaerobic coverage |
Trovafloxacin |
3. Antimicrobial activity and mechanisms of bacterial resistance
3.1 Mode of action:
The quinolones inhibit bacterial enzyme topoisomerases, including topoisomerase II (otherwise known as DNA gyrase) and topoisomerase IV. Bacterial DNA supercoils and then uncoils during replication. Supercoiling requires transient nicks that are subsequently sealed after DNA polymerase passes. Topoisomerase II allows for single strand nicks in the DNA that support coiling and uncoiling. Topoisomerase IV supports disentanglement of DNA as chromosomes separate. Inhibition of topoisomerases reduces supercoiling, resulting in disruption of the spatial arrangement of DNA, and reduces DNA repair. Mammalian topoisomerase enzymes fundamentally differ from bacterial gyrase and are not susceptible to quinolone inhibition. The quinolones are usually bactericidal; susceptible organisms lose viability within 20 min of exposure to optimal concentrations of the newer fluoroquinolones. Quinolones are associated with a postantibiotic effect in a number of bacteria, principally gram-negative (eg, E coli, Klebsiella pneumoniae, P aeruginosa). The effect generally lasts 4–8 hr after exposure.
3.2 Bacterial resistance:
There are three mechanisms that decrease the sensitivity of bacterial cells to quinolones. Target-mediated resistance is the most common and clinically significant form of resistance. It is caused by specific mutations in gyrase and topoisomerase IV that weaken interactions between quinolones and these enzymes. Plasmid-mediated resistance results from extrachromosomal elements that encode proteins that disrupt quinolone–enzyme interactions, alter drug metabolism, or increase quinolone efflux. Chromosome-mediated resistance results from the underexpression of porins or the overexpression of cellular efflux pumps, both of which decrease cellular concentrations of quinolones.
4. The harm of veterinary drug residues
According to research, adverse reactions (ADR) caused by FQs drugs can damage the skin system, nervous system, reproductive system, urinary system, endocrine system and digestive system, and show different clinical symptoms depending on the route of administration, dose, duration and type of drugs. In feed processing, animal production, food processing, etc, due to the lack of knowledge caused by excessive use of drugs and don't take medicine, one-sided pursuit of economic benefits, even for the corrosion protection of meat and its products in excess of antimicrobial agents and so on all can lead to FQs through the food chain in the human body, cause harm to human body.
5. Introduction of our products
100009 - Fluoroquinolones Rapid Test Kit
100020 - TriTest LQT Rapid Test Kit
100024 - QuaTest QMLE Rapid Test Kit
