Fluoroquinolone Antibiotics

Abstract

The newer fluoroquinolones are a major advance in antimicrobial chemotherapy. They inhibit the supercoiling activity of the DNA gyrase enzyme, thus exerting their antibacterial action on DNA and RNA synthesis, resulting in a biphasic response and killing of susceptible organisms. The newer fluoroquinolones have an extended antimicrobial spectrum compared to their older congeners, and are highly active against most Gram-negative pathogens including the Enterobacteriaceae and Pseudomonas aeruginosa. While Staphylococcus aureus and coagulase-negative staphylococci are usually susceptible to the fluoroquinolones, streptococci are generally more resistant and enterococci are resistant. All of the newer fluoroquinolones may be administered orally and most of them have been administered parenterally. They are widely distributed in the body, attaining therapeutic concentrations in most tissues. All of the fluoroquinolones have long half-lives and may be administered once or twice daily. The fluoroquinolones have proved effective in many infections, including uncomplicated or complicated urinary tract infections, respiratory tract infections, gonorrhoea, bacterial gastroenteritis, and soft tissue infections due to Gram-negative organisms. In general, success has been notable in the management of Gram-negative infections but less so with Gram-positive infections. Resistance has occurred and is proving a problem with P. aeruginosa in some cystic fibrosis patients, but as yet no plasmid-mediated resistance has developed. Cross-resistance occurs between the quinolones but only rarely with other classes of antibacterial drugs. The fluoroquinolones have an excellent safety record and their adverse effects, which include hypersensitivity reactions, dizziness, headache, gastrointestinal disturbance and minor haematological abnormalities are usually mild and transient. However, the fluoroquinolones have been found to damage juvenile weight-bearing joints in animals and are therefore only to be used with caution in children; transient arthralgia has been reported in a cystic fibrotic teenager on long term ciprofloxacin therapy. All of the fluoroquinolones except ofloxacin are associated with a variable increase in the serum concentration of theophylline, warfarin and caffeine. Thus, the fluoroquinolones are an attractive option in the management of many infections. Cost and possible resistance, however, should counsel caution in their use, and may limit them to situations where a cheaper antimicrobial of equivalent efficacy is not available.

Ofloxacin-like Antibiotics Inhibit Pneumococcal Cell Wall-degrading Virulence Factors

“…Their targets are, preferentially, DNA gyrase in the case of Gram-negative and topoisomerase IV among the Gram-positive bacteria (42,43). The development of these antibacterial agents was the result of intense research aimed at improving the stability, decreasing the affinity and broadening the activity spectrum of the lead compounds 7-chloroquinoline and nalidixic acid.…”

<p>Vitamin D Pretreatment Attenuates Ciprofloxacin-Induced Antibacterial Activity</p>

“…6 Of the fluoroquinolones, ciprofloxacin is the most potent fluoroquinolone against gram-negative bacteria (mainly the Enterobacteriaceae species such as Escherichia coli, Salmonella, Shigella, and Neisseria). 5,7 Since its introduction, ciprofloxacin was found to be effective for a variety of bacterial infections including urinary tract infections (both complicated and uncomplicated), intra-abdominal infections, skin and bone infections, gynecological infections and sinusitis. 1,8 Ciprofloxacin is one of the few oral antimicrobials that is used to treat pseudomonas aeruginosa.…”

Fluoroquinolone-Resistant Enteric Bacteria in Sub-Saharan Africa: Clones, Implications and Research Needs

“…This first quinolone was the base molecule used to synthesize the even more active fluoroquinolones, which also had more favorable pharmacokinetics (Mitscher, 2005 ). First generation fluoroquinolones (second generation quinolones), like ciprofloxacin, became clinically available in the 1980s and were patent protected until the 2000s (Paton and Reeves, 1988 ). Until recently, ciprofloxacin was the most potent fluoroquinolone and highly active against virtually all bacterial enteropathogens.…”