Fluoroquinolones

WIKIDRUGS ANTIBIOTICS

Nalidixic Acid - The Parent Drug of the Fluoroquinolones

The parent drug of the quinolone family was Nalidixic acid, this was found to be very narrow spectrum. It worked well only against gram negative enterobacteriaceae and resistance quickly developed. This limited it's use now for just urinary tract infections and for treatment of Aeromonas salmonicida in fish. Due to the restricted spectrum of the quinolones fluoroquinolones were developed to increase the range. The most commonly used in practice are Enrofloxacin, Marbofloxacin, Danofloxacin, Difloxacin, Ibafloxacin and Orbifloxacin.

Mechanism of Action

Fluoroquinolones work by inhibiting bacterial DNA gyrase or the topoisomerase enzyme and thus inhibit bacterial DNA replication and transcription. The gyrase enzyme is usually the target in gram-negative bacteria, whilst the topoisomerase enzyme is the target in most gram-positive bacteria. This kills the bacteria and so the drug is a bactericidal and concentration dependent.

These drugs also have the ability to cross animal's cell membranes through porins. This means that this group of drugs is capable of acting upon intracellular pathogens.

Spectrum of Activity

• Active against gram-negative species including aerobic species such as Pseudomonas aeruginosa.
• Active against gram-positives (doesn't work that well against Streptococcal species and enterococci.)
• Works well against Mycoplasmas and Rickettsia.
• Poor activity against obligate anaerobes.
• Their activity is very pH dependent wit their activity increasing above pH 7.4 and decreasing below pH 7.0.

It should be noted that they are active at very low concentrations, they don't kill protective enterococci and anaerobes, and they will inhibit aminoglycoside and beta-lactam resistant bacteria.

Pharmacokinetic Considerations

• They are highly lipophilic and have a low degree of ionisation.
• They are well absorbed from the gastrointestinal tract.
• It isn't very well protein bound and so