Quinolone antibiotics
Quinolone antibiotics are synthetic antibacterial agents derived from nalidixic acid, which itself is a by-product of the antimalarial compound quinine. This class of antibiotics includes the original quinolones and more advanced fluoroquinolones, such as ciprofloxacin, moxifloxacin, and levofloxacin, which have a broader spectrum of activity and enhanced pharmacological properties. Quinolones work by interfering with bacterial DNA replication, leading to cell death, and are characterized by their high bioavailability, allowing for effective oral or intravenous administration.
These antibiotics are commonly used to treat a variety of infections including urinary tract infections, respiratory tract infections, and certain eye infections. While they are generally considered safe, mild side effects can occur, such as nausea and headache, while more serious reactions, including tendon damage and central nervous system effects, are less common. The emergence of antibiotic-resistant bacteria, particularly due to the overuse of quinolones, poses a significant public health challenge, prompting the development of newer quinolones aimed at overcoming resistance and minimizing side effects.
Quinolone antibiotics
Definition
Quinolone is a synthetic antibacterial (antibiotic) drug not of microbial origin. Its synthetic origin stems from nalidixic acid, a by-product of the antimalarial compound quinine. The original quinolones consisted of nalidixic acid, cinoxacin, and oxolinic acid, but they were of limited use. Chemical modifications of these antibiotics produced an improved class of potent antibiotics known as fluoroquinolones. Fluoroquinolones are divided into groups based on their broad spectrum of activity and pharmacological properties. The best-known fluoroquinolones include ciprofloxacin (Cipro), moxifloxacin (Avelox), and levofloxacin (Levaquin).
Mode of Action
Quinolones generally exhibit concentration-dependent bactericidal tendencies. These agents interfere with bacterial deoxyribonucleic acid (DNA) replication and cause cell death. During this process, the antibiotic binds to and induces a conformational change in complexes created by bacterial DNA and the enzymes essential for their DNA replication, gyrase and topoisomerase. The bactericidal mechanism occurs at high antibiotic concentrations, with the release of free DNA ends from the antibiotic-gyrase-DNA complexes.
Pharmacology
The ability of an antibiotic to successfully inhibit infectious bacteria depends on its pharmacological profile. The most significant attribute of quinolones is their high bioavailability. These antibiotics are rapidly distributed into bodily fluids, show increased tissue absorption, have shorter dosing regimens, and are equally effective as oral or intravenous therapy.
Indications
The quinolone antibiotics are active against a broad range of pathogens, including gram-positive and gram-negative bacteria, mycobacteria, atypical pathogens, and some anaerobes. Clinical applications of these antibiotics include treating urinary tract infections, including bacterial prostatitis; gynecological infections; sexually transmitted diseases; gastrointestinal infections, such as bacterial diarrhea; and respiratory tract infections. Several fluoroquinolones are established as ophthalmic agents used to treat bacterial eye infections such as conjunctivitis. One of the best-known fluoroquinolones, ciprofloxacin, is known for its use against anthrax infections. Ciprofloxacin is also recognized for its effectiveness in treating respiratory infections in cystic fibrosis patients. Quinolones are also often used in patients with weakened immune systems.
Side Effects
Quinolones are relatively safe with mild side effects that include nausea, headache, dizziness, and confusion. Serious side effects are uncommon but can occur and include seizures, convulsions, hallucinations, phototoxicity, heart arrhythmias, and hepatotoxicity (liver damage). Quinolones are not recommended for persons with central nervous system disorders or epilepsy. Quinolones have also been linked to tendinitis and tendon rupture, and their use is limited among children because of the risk of joint abnormalities. These agents also have an increased association with a severe secondary colon infection caused by the bacterium Clostridium difficile following antibiotic use.
Impact
The emergence of quinolone-resistant strains of bacteria continues to be a worldwide concern. Although quinolones have evolved into a highly effective and valuable class of antibacterial agents, their continued overuse in clinical and veterinary medicine has limited their future effectiveness. Because of this likelihood of resistance, newer quinolones have been developed and are usually reserved for serious infections. Examples of newer quinolones include delafloxacin, which was approved in 2017 and is effective against methicillin-resistant Staphylococcus aureus (MRSA) infections. Also approved in 2017, finafloxacin has shown effectiveness in treating ear infections. Several additional quinolones were undergoing clinical trials in the twenty-first century. Although resistance remained an immediate public health concern, newer quinolones were designed to overcome resistance, present more targeted therapies, and cause fewer side effects.
Bibliography
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