The quinolones and fluoroquinolones form broad a class of antibiotics of synthesis which include/understand the derivatives of the nalidixic Acide discovered in 1962 and used at the man as of the following year. This antibiotic class was the subject of very important research leading to the deposit of more than 10000 patents. The addition of the fluorine atom in the years 1970 made it possible to strongly increase the penetration of the molecules quinolones in the cells (up to 200 times more): it was the birth of the fluoroquinolones, powerful antibiotics able to fight against a large variety of germs in the man and the animal (including in pisciculture (Asia in particular), although this antibitotic is interdict for this use in many countries).

The appearance on the market in the years 1980 of the Norfloxacine, Ofloxacine, Ciprofloxacine, Péfloxacine and Loméfloxacine made it possible the Fluoroquinolones to become antibiotics of reference for many infections, like the acute pyelonephritides or the prostatitises.

Serious side effects

These substances, largmenent used by certain breedings (Asian fish cats for example) generate many side effects, of which sometimes of heavy temporary or final disabilities. Tendineux effects, going until the rupture of tendon (S) in various places of the body were announced since 1983. Years 1990 will be remembered by an exemplary crisis of confidence on behalf of the prescribers, in particular in France. The tests on the animals show moreover one carcinogenic potential on all the mammals and teratogenic on the rat, of serious cartilagineuses attacks on the majority of the immature mammals.

In 1997, the article of the team of the French specialists Marcel-François Kahn and Gilles Hayem, " Tendons and fluoroquinolones: unsolved problems " described the tendineux effects of the fluoroquinolones. The péfloxacine, shown since years to cause many tendinopathies, will become marginal.

Use, and evolution of the molecules

About half of the quinolones marketing saw themselves withdrawing or restricting their license of use, but about 1998, the sales of fluoroquinolones increase and even will explode as from 2001, with the appearance of products of new generation.

At the end of 2001, the psychosis of the bioterrorism after the attacks of September 11th pushes many people to be protected from the bacillus from coal using products containing ciprofloxacine or of ofloxacine, multiplying the daily sales of these antibiotics by 10. It is what certain called the hour of glory of the fluoroquinolones.

In March 2006, the Economic Committee of the Health products will estimate that the fluoroquinolones are prescribed too much in France, and will require laboratories manufacturers that the time of medical visit which to them is devoted either tiny room of 30% over 3 years.

Research aims today new generations of quinolones at spectrum of action still widened, but with less side effects. The fluorine being a probable cause of their toxicity, one seeks to create close molecules, but without fluorine (défluoroquinolones) very different from the first generation of quinolones.

Mode of action

The quinolones target the DNA-gyrase and the topoisomérase IV, preventing the replication of bacterial DNA. Some speak about " trucage" DNA.

Classification of Quinolones

1st generation

• Acid nalidixic (Negram®, Negram Forte®)

• Acid pipemidic (Pipram®, Pipram Forte®)
• Acid oxolinic
• Fluméquine
• Cinoxacine

2nd generation

• Ciprofloxacine (Ciflox®, Cipro®)
• Ofloxacine (Oflocet®, Monoflocet®, Tarivid®, Ocuflox®, Floxin®)
• Norfloxacine (Noroxine®)
• Loméfloxacine (Logiflox®, Décalogiflox®)
• Péfloxacine (Péflacine®)
• énoxacine (Enoxor®, Penetrex®)

3rd generation

• Isomer Lévofloxacine of the ofloxacine (Tavanic®, Levaquin®)

• Sparfloxacine (Zagam®)
• Grépafloxacine
• Gatifloxacine

4th generation

• Trovafloxacine (Trovan ®)

• Moxifloxacine (Izilox®)
• Gémifloxacine (Factive®)
• Sitafloxacine
• Clinafloxacine

Resistances to the quinolones

One observes an increase in resistance to some fluoroquinolones largely distributed like the ciprofloxacine. Several assumptions are advanced:

- As it was the case for other antibiotic classes in the past, the important volume of regulation in particular in hospital medium supports bacterial resistances.

- The massive use of fluoroquinolones veterinary would support the selection of resistant microbial stocks in the environment.

The effectiveness of antibiotics of second generation in the infections would be from 60 to 95%, the variation coming from the type of germ concerned.

Among the resistant bacteria, one can quote: Aerobes with Gram-plus: entérocoques, Listeria monocytogenes, Nocardia asteroids, staphylococcus méti-R.

Counter-indications

• Child or teenager in growth (risk of attack of the Cartilage S).
• pregnant Woman or nursing (risks of malformation).
• Previous of Tendinopathie under fluoroquinolones.

Precautions for use

The benefit-risk ratio must be more particularly evaluated at the insufficient renal ones and the people taking an even inhaled concomitant corticothérapie.

In the adult of less than 30 years, occurred of Arthropathie S is to be supervised closely.

In the adult of more than 65 years, the risk of tendinopathy is very clearly raised.

Undesirable effects

The fluoroquinolones can cause very diverse side effects, of which the effects of class are the joint base. The molecules fluoroquinolones can remain several months in the body, which would explain why certain side effects as photosensitization can appear a long time after the catch:

• tendinopathies being able to go until the tendineuse rupture in particular to the Tendon of Achilles but also to the shoulders, knees, hands, Arthralgie S; articular crackings, Osteoarthritis, Arthritis, myalgias, Rhabdomyolyse, oedemas, fasciculations.

• cutaneous demonstrations: exfoliative Photosensitization, Dermatite, Syndrome of Lyell, Prurit, erythema, cicatrization of bad quality, opportunist infection by Staphilococcus gilded.
• digestive demonstrations: nauseas, vomiting, Gastralgie S.
• neurological demonstrations: convulsions, mental confusion, hallucinations, nightmares, Cephalgias, eye trouble of which Diplopia, Photophobia, perception of the colors modified, giddinesses, paraesthesias, sleep disorders, possible aggravation of Myasthénie, depression, ideas suicidal, depersonalization, Acouphènes, metal taste, modified sense of smell.
• cardiac symptoms: lengthening of space QT, palpitation, Tachycardia, extrasystoles, auricular Fibrillation, ventricular Fibrillation, Heart attack.
• hepatic demonstrations: increase in the transaminases, Hepatitis, Jaundice.
• urogenital demonstrations: Impotence, Hyperurémie, mycoses, Hématurie microscopic or macroscopic.
• hematologic demonstrations: Hyperplaquettose, Thrombocytopenia, Leucopenia.

Allergy/over-sensitiveness

• allergic demonstrations: anaphylactic Urticaria, exceptionally edema of Quincke and shock of the type.

The business of Trovan

Washington Post will make state on May 7th, 2006 of a report/ratio of the Nigerian authorities blaming the world pharmaceutical leader Pfizer who would have practiced an illegal test of the Trovafloxacine (Trovan ®) in 1996 on nearly 200 children and infants at the time of an epidemic of meningitis, causing deaths and heavy handicaps in particular dependant on arthritis. Pfizer will affirm to have obtained the oral agreement of the families of the children. It will be learned at the beginning of June 2007 that Nigeria claims 7 billion dollars of repair at Pfizer.

Journalists affirm that this business, largely spread since 2000, would have inspired " The constancy of the jardinier" with John the Square. The drug concerned, a Fluoroquinolone having 3 fluorine atoms, will be put on the market in 1998 in Europe before being prohibited because of serious hepatic effects.

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