Generality
Fluoroquinolones are antibacterial drugs used in the treatment of different types of infections.
In detail, the quinolone antibacterial drugs that, within their chemical structure, have one or more fluorine atoms (from which, precisely, the prefix "fluoro-") fall into the group of fluoroquinolones.
Fluoroquinolones exert a broad spectrum bactericidal action, therefore, they are effective in counteracting infections sustained both by Gram-positive bacteria and Gram-negative bacteria.
Depending on the case, fluoroquinolones can be administered orally, parenterally, inhaled, via the eye (eye drops, ophthalmic ointment) or ear (ear drops). Medicines containing fluoroquinolones can only be dispensed upon presentation of a specific prescription. Depending on the pharmaceutical formulation and the type of active ingredient contained in the medicinal product, the medical prescription can be repeatable or restrictive (sold to the public on prescription from hospitals or specialists). Furthermore, it is worth remembering that some fluoroquinolone based medicinal products are exclusively for hospital use.
What are
What are Fluoroquinolones and What are they for?
Fluoroquinolones are antibacterial drugs of synthetic origin capable of exerting a bactericidal activity against various micro-organisms, both Gram-positive and Gram-negative (broad spectrum of action).
The discovery of the fluoroquinolones aroused an immediate enthusiasm because of their wide spectrum of action; enthusiasm that, nevertheless, has gradually diminished due to the appearance of resistance phenomena and the discovery of problems with regard to their safety of use (more detailed information can be found in the dedicated chapters "Toxicity" and "Resistance"). Despite this, there are several active ingredients belonging to the group of fluoroquinolones still used today in therapy.
Which active principles belong to the group of fluoroquinolones?
The active ingredients belonging to the group of fluoroquinolones are many, however, some of them are no longer used in therapy because of the toxicity phenomena that emerged after their release on the market. However, among the active ingredients still used, we recall:
- Ciprofloxacin (oral, parenteral, auricular and ocular administration);
- Levofloxacin (oral, parenteral, inhalation and ocular administration);
- Ofloxacin (oral, parenteral and ocular administration);
- Moxifloxacin (oral and ocular administration);
- Norfloxacin (oral and ocular administration);
- Pefloxacin (oral administration);
- Lomefloxacin (oral administration);
- Prulifloxacin (oral administration).
Therapeutic indications
When are Fluoroquinolones used?
Of course, since these are antibacterial drugs, the use of fluoroquinolones is indicated in the treatment of different types of infections sustained by microorganisms sensitive to the same fluoroquinolones, among which we recall:
- Chlamydia spp .;
- Mycoplasma spp .;
- Chlamydophila spp .;
- Legionella spp .;
- Mycobacterium tuberculosis ;
- Haemophilus influenzae ;
- Pseudomonas aeruginosa ;
- Moraxella catarrhalis ;
- Enterobacteriaceae;
- Some atypical mycobacteria;
- Methicillin-sensitive staphylococci (methicillin-resistant staphylococci, on the other hand, are usually resistant to fluoroquinolones).
The most recent fluoroquinolones also appear to be quite effective against streptococci, including S. pneumoniae with reduced sensitivity to penicillin.
Infections can be treated with Fluoroquinolones
The infections sustained by the above listed microorganisms treatable with fluoroquinolones, are:
- Urinary tract infections;
- Gastrointestinal infections;
- Intra-abdominal infections;
- Lung and airway infections;
- Paranasal sinus infections;
- Ear infections;
- Eye infections;
- Infections of the genital apparatus;
- Skin and soft tissue infections;
- Bone and joint infections.
Finally, we recall that fluoroquinolones can also be used in prophylaxis after exposure to anthrax spores and in the curative treatment of anthrax.
Action mechanism
How Do Fluoroquinolones Work?
Fluoroquinolones perform their bactericidal action by inhibiting the activity of two enzymes fundamental for cell replication: DNA-gyrase and topoisomerase type IV . These are enzymes involved in the supercoiling, rewinding, cutting and welding of bacterial DNA. With the inhibition of the aforementioned enzymes, the bacterial cell can no longer access the information contained within the genes; all cellular processes - including replication - fail and the microorganism dies.
Please note
Each fluoroquinolone is able to inhibit the activity of the aforementioned enzymes with different strength.
Side effects
What undesirable effects can occur when taking Fluoroquinolones?
Since the active ingredients that are part of the group of fluoroquinolones are multiple, it is difficult to make an exhaustive list of all the side effects that may occur during therapy with this type of antibacterial agent, since there may be some variability from active ingredient to active ingredient. Therefore, only some of the side effects common to most fluoroquinolones will be reported below:
- Allergic reactions in sensitive individuals;
- Gastrointestinal disorders, the most common are:
- Nausea;
- He retched;
- Abdominal pains;
- Diarrhea.
- Nervous system disorders and psychiatric disorders, such as:
- Headache;
- Dizziness;
- Drowsiness;
- Peripheral neuropathy (requires suspension of fluoroquinolone);
- Insomnia;
- Motor restlessness;
- Mood changes.
- Tendinopathy and joint disorders ;
- Cardiac disorders, including in particular the lengthening of the QT interval which, in turn, can lead to ventricular arrhythmias and sudden cardiac death.
Pregnancy and breastfeeding
Can Fluoroquinolones be used during pregnancy and during breastfeeding?
Although we cannot speak of a contraindication in the strict sense, the use of fluoroquinolones during pregnancy and breastfeeding is NOT generally recommended due to the negative effects these drugs can exert on the fetus (reach the placenta) and in the child ( are excreted in breast milk).
Contraindications
When Fluoroquinolones MUST NOT be Used
Similarly to what was said for the side effects, also the contraindications could vary depending on the active principle taken into consideration. However, in general, it is possible to state that the use of fluoroquinolones is contraindicated in the following cases:
- Known hypersensitivity to the active ingredient and / or to one or more of the excipients contained in the medicinal product that should be used;
- Presence of disorders that predispose to the onset of cardiac arrhythmias ;
- Concomitant use of other drugs that may induce an increase in the QT interval .
The administration of fluoroquinolones in children is not expressly contraindicated, however, it should only occur in the presence of specific infections and health conditions and, in any case, should not be considered as first line drugs for the pediatric category.
Please note
For more in-depth information on indications, warnings and precautions, interactions, side effects, use during pregnancy and during lactation and contraindications of the different fluoroquinolones, please refer to the careful reading of the illustrative leaflet of the medicinal product that you need to use and which was prescribed by the doctor.
Toxicity
Toxicity and Serious Side Effects induced by some Fluoroquinolones
Over the years, after entering therapy, numerous fluoroquinolones have been withdrawn from the market due to the appearance of toxicity and serious side effects on various organs and tissues. Going into more detail:
- The temloxacin has been withdrawn from the market because it is capable of causing haemolysis, thrombocytopenia and renal damage (hemolytic-uremic syndrome);
- Trovafloxacin has been withdrawn as responsible for the onset of severe liver toxicity;
- Grepafloxacin was withdrawn from the market because its intake was a cause of cardiovascular toxicity;
- Gatifloxacin has been withdrawn because it is responsible for the onset of hypoglycemia or hyperglycaemia.
- Sparfloxacin has been withdrawn from the market as capable of inducing nephrotoxicity and phototoxicity.
In the United States, lomefloxacin has also been withdrawn from the market, while in Italy it is still used in therapy.
Did you know that ...
At the beginning of October 2018, the EMA (European Medicines Agency) Risk Assessment Committee for Pharmacovigilance recommended the adoption of restrictions on the use of both fluoroquinolones and quinolones due to the appearance of undesirable effects of long lasting and invalidating that occurred in several patients. In detail, the EMA recommends using this type of antibiotics with caution, preferably in the presence of severe infections and / or when the usually recommended antibiotic / antibacterial drugs cannot be used or are ineffective.
However, for more information on this, it is advisable to consult your doctor.
Resistance
Fluoroquinolone Resistance Phenomena
Bacteria are able to develop resistance to both fluoroquinolones and quinolones. To do this, they seem to use two main mechanisms:
- Spontaneous mutation of genes (gyrA and gyrB) that encode DNA-gyrase: due to these mutations, the bacteria produce DNA-gyrases that are not inhibited by fluoroquinolones;
- Alterations and variations in the permeability of the cell membrane that can lead to a lower entry of fluoroquinolones inside the bacterial cell, or to a greater output of the same from the microorganism (this latter mechanism seems to be more significant in Gram-negative microorganisms).
