home Auditorium 8 Fluoroquinolones of the third generation. Fluoroquinolones antibiotics drug names

Fluoroquinolones of the third generation. Fluoroquinolones antibiotics drug names

Fluoroquinolones - drugs belong to the group of quinolones and have antibacterial properties. Used in clinical practice of pulmonology, otolaryngology, urology, nephrology, dermatology, ophthalmology. The breadth of application is due to the spectrum of action and effectiveness of these drugs. However, they have a number of negative influences. Timely prescription of antibiotics strictly according to indications, in proper dosages, taking into account contraindications, ensures the effectiveness and safety of therapy.

Approaches to systematization

The list of drugs of various fluoroquinolones and quinolones includes about 4 dozen drugs. They are divided by the presence or absence of a fluorine atom, by its quantity in the molecule (monophthoquinolones, diphthoquinolones), by the predominant spectrum of action (gram-negative, anaerobic), and area of application (respiratory).

The most complete picture is contained in the classification of quinolones into separate generations. This is the approach that is common in practice.

General classification of quinolones:

1st generation (non-fluorinated): nalidixic acid, oxolinic acid;
2nd generation (gram-negative): ciprofloxacin, norfloxacin, ofloxacin, lomefloxacin;
3rd generation (respiratory): levofloxacin, sparfloxacin, gatifloxacin;
4th generation (respiratory and antianaerobic): moxifloxacin, gemifloxacin.

Differences in chemical characteristics, spectrum of pathogens, and interaction with the patient’s body determine the place of each drug in therapy.

Pharmacological features

The mechanism of action of the drugs is due to the effect on bacterial enzymes involved in the formation of DNA and RNA. The result is an irreversible disruption of the synthesis of protein molecules of the microbial cell. Its viability decreases, the activity of toxic and enzymatic structures decreases, and the likelihood of the bacterial cell being captured by a phagocyte (an element of the human defense system) increases.

Fluoroquinolones prevent bacterial cell division

Representatives of all groups of fluoroquinolones influence the active bacterial cell and are also capable of disrupting any stage of its life cycle. They act on growing microorganisms and on cells at rest, when most medications are ineffective.

The therapeutic effect of fluoroquinolones is due to:

bactericidal effect;
penetration into the bacterial cell;
continuation of the antimicrobial effect after cessation of contact with the drug molecule;
creating high concentrations in the patient’s tissues and organs;
long-term removal of the drug from the body.

Nalidixic acid is the first member of the quinolones. The second drug was oxolinic acid, which had 3 times more activity than its predecessor. However, after the creation of 2nd generation fluoroquinolones (ciprofloxacin, norfloxacin), this drug is practically not used.

Of the quinolones, only nalidixic acid (nevigramone) is currently used. Indicated for infections urinary tract(pyelitis, cystitis, prostatitis, urethritis), to prevent intraoperative complications on the kidneys, ureter, bladder. Take up to 4 times a day (tablets).

Fluoroquinolones, like the next generation of quinolones, show changes in the spectrum of sensitive microbes, as well as pharmacokinetic properties (absorption, distribution and excretion from the body).

General advantages of fluoroquinolones compared to quinolones:

broad antimicrobial activity;
effective concentrations in internal organs when using tablet forms, independent of food intake;
good penetration into the respiratory organs, kidneys, urinary system, ENT organs;
to maintain therapeutic concentrations in the affected tissues, it is enough to prescribe 1-2 times a day;
side effects in the form of disruption of the digestive system, nervous system occur less frequently;
are used for impaired renal function, although their excretion slows down with this pathology.

Today there are four generations of representatives of this group.

Application in clinical practice

The drugs have a very wide spectrum and act on most microorganisms. 2nd generation drugs predominantly affect aerobic gram-negative bacteria (salmonella, shigella, campylobacter, gonorrhea pathogen), gram-positive (tuberculosis pathogen).

At the same time, pneumococcus, opportunistic microorganisms (chlamydia, legionella, mycoplasma), as well as anaerobes are insensitive to them. Since pneumococcus is the main causative agent of pneumonia and often affects the ENT organs, the use of these drugs in otolaryngology and pulmonology has limitations.

Norfloxacin (2nd generation) has a wide spectrum of effects, however, it creates high therapeutic concentrations only in urinary system. Therefore, the scope of its application is limited to nephrological and urological pathology.

Respiratory fluoroquinolones (3rd generation) have the same spectrum of influence as the drugs of the previous group, and also have an effect on pneumococci, including stable forms, for atypical microbes (chlamydia, mycoplasma). This made it possible to widely begin to use this group for treatment respiratory system(respiratory organs), as well as in general therapeutic practice.

Third generation fluoroquinolones are used to treat infections:

Fluoroquinolones of the 4th generation, the latest generation to date, have an effect on gram-positive, gram-negative flora, and are also effective against anaerobes that are not capable of sporulation. This expands the scope of their application, allows them to be used for deep injuries skin with development anaerobic infection, aspiration pneumonia, intra-abdominal, pelvic infections.

The advantage of modern fluoroquinolones is the ability to use only this medicine (monotherapy).

They are indicated for the same diseases as respiratory fluoroquinolones. At the same time, moskifloxacin affects resistant strains of staphylococci, and therefore can be used in the treatment of the most severe hospital-acquired pneumonia.

The great advantage of a number of these drugs (levofloxacin, pefloxacin) is the possibility of their use not only for oral administration, but also for intravenous administration. This ensures rapid delivery of the drug to the affected tissues, which can be decisive for severe patients. It is also possible to use so-called step therapy. When, upon receiving a positive result from the infusion method of administering the medication, they switch to tablet forms. High Availability fluoroquinolones with this method of administration ensures effectiveness and helps to avoid negative consequences administration of large volumes of drugs intravenously.

Undesirable effects and contraindications for use

Like any medicines, fluoroquinolones antibiotics have a number of side effects. They must be distinguished from changes in the patient’s condition that are caused by the underlying disease (for example, a temporary increase in body temperature) and indicate therapeutic effect medicines.

List of side effects:

It is also extremely rare that pseudomembranous colitis develops with severe dysbiosis or intestinal damage by clostridia. It's hard and dangerous disease intestines. Therefore, if there are changes in stool, bloody or other impurities in the stool, or a wave of temperature that cannot be explained by the underlying disease, you should urgently consult a doctor.

Contraindications:

pregnancy at any stage;
breastfeeding period;
age less than 18 years;
allergy or reaction to taking quinolones and fluoroquinolones in the past.

Fluoroquinolones are not used to treat children due to severe negative influence on cartilage tissue growing organism.

If necessary, these drugs are replaced with medications with a similar spectrum of influence on pathogens.

In case of heart disease with a threat of development of ventricular arrhythmias, or pathology of the liver and kidneys, it is necessary to carefully monitor the condition of these organs.

U various drugs the range of possible negative impacts is different. Therefore, the use of these drugs should be under the strict supervision of a physician.

The use of fluoroquinolones in diseases of the ENT organs

For inflammatory diseases of the nasal passages, oropharynx, tonsils, paranasal sinuses, ear infectious nature use drugs penicillin series, macrolides, cephalosporins and fluoroquinolones.
3rd and 4th generation drugs are used: levofloxacin, moxifloxacin, sparfloxacin. The advantage of these generations of drugs is that they affect pneumococci. It is these streptococci that in most cases are the causative agents, either alone or together with other microbes inflammatory diseases ENT organs, respiratory system.

Used for acute and chronic inflammatory processes caused by fluoroquinolone-sensitive antibiotics.

Most often used in therapy:

diseases of the paranasal sinuses;
rhinitis;
rhinosinusitis.

Fluoroquinolones are used when there is no effect from treatment with beta-lactams (penicillins and cephalosporins) and macrolides.

Thus, drugs of the fluoroquinolone group are among the most widely used in modern medicine. antibacterial therapy adults. Thorough examination of the patient, identification of risks of negative effects, the most accurate selection of the drug for the microbial spectrum of pathogens specific disease, determining the method and mode of administration ensures the positive effect of therapy, as well as its safety.

Quinolones- group antibacterial drugs, also including fluoroquinolones. Quinolones are a group of synthetic antimicrobial drugs that have a bactericidal effect. The first quinolone drug was nalidixic acid, synthesized in 1962 from naphthyridine. The first drugs in this group, primarily nalidixic acid, were used for many years only for urinary tract infections.

Based on the same mechanism of antimicrobial action, quinolones and fluoroquinolones received the general name “DNA gyrase inhibitors.”

Since its introduction into practice in the 1990s. A number of quinolone analogues have been prepared for ciprofloxacin.

The main contraindications to the use of fluoroquinolones are related to the hypersensitivity of patients to quinolone drugs (quinolones and fluoroquinolones)

Drugs of the quinolone class, used in clinical practice since the early 60s, have a mechanism of action that is fundamentally different from other AMPs, which ensures their activity against resistant, including multiresistant, strains of microorganisms. The class of quinolones includes two main groups of drugs that differ fundamentally in structure, activity, pharmacokinetics and breadth of indications for use: non-fluorinated quinolones and fluoroquinolones. Quinolones are classified according to the time when new drugs with improved antimicrobial properties were introduced into practice. According to the working classification proposed by R. Quintiliani (1999), quinolones are divided into four generations:

Classification of quinolones

I generation:

Nalidixic acid

Oxolinic acid

Pipemidic (pipemidic) acid

II generation:

Lomefloxacin

Norfloxacin

Ofloxacin

Pefloxacin

Ciprofloxacin

III generation:

Levofloxacin

Sparfloxacin

IV generation:

Moxifloxacin

The listed drugs are registered in Russia. Some other drugs of the quinolone class are also used abroad, mainly fluoroquinolones.

First generation quinolones are predominantly active against gram-negative flora and do not create high concentrations in the blood and tissues.

Fluoroquinolones approved for clinical application since the early 80s (II generation), they are distinguished by a wide spectrum of antimicrobial action, including staphylococci, high bactericidal activity and good pharmacokinetics, which allows their use for the treatment of infections various localizations. Fluoroquinolones, introduced into practice since the mid-90s (III-IV generation), are characterized by higher activity against gram-positive bacteria (primarily pneumococci), intracellular pathogens, anaerobes (IV generation), as well as even more optimized pharmacokinetics. The presence of a number of drugs in dosage forms for intravenous administration and oral administration, combined with high bioavailability, allows step therapy, which, with comparable clinical effectiveness, is significantly cheaper than parenteral.

The high bactericidal activity of fluoroquinolones made it possible to develop them for a number of drugs (ciprofloxacin, ofloxacin, lomefloxacin, norfloxacin) dosage forms For local application in the form of eye and ear drops.

Mechanism of action

Quinolones have a bactericidal effect. Inhibiting two vital important enzyme microbial cell - DNA gyrase and topoisomerase IV, disrupt DNA synthesis.

Activity spectrum

Non-fluorinated quinolones act predominantly against gram-negative bacteria of the family Enterobacteriaceae
(E.coli, Enterobacter spp., Proteus spp., Klebsiella spp., Shigella spp., Salmonella spp.), as well as Haemophilus spp. And Neisseria spp. Oxolinic and pipemidic acids are also active against S. aureus and some strains P. aeruginosa, but this has no clinical significance.

Fluoroquinolones have a much wider spectrum. They are active against a number of gram-positive aerobic bacteria (Staphylococcus spp.), most gram-negative strains, including E.coli(including enterotoxigenic strains), Shigella spp., Salmonella spp., Enterobacter spp., Klebsiella spp., Proteus spp., Serratia spp., Providencia spp., Citrobacter spp., M. morganii, Vibrio spp., Haemophilus spp., Neisseria spp., Pasteurella spp., Pseudomonas spp., Legionella spp., Brucella spp., Listeria spp.

In addition, fluoroquinolones are usually active against bacteria resistant to first generation quinolones. Fluoroquinolones of the third and, especially, fourth generation are highly active against pneumococci, more active than drugs of the second generation against intracellular pathogens ( Chlamydia spp., Mycoplasma spp., M. tuberculosis, fast growing atypical mycobacteria (M.avium and etc.), anaerobic bacteria(moxifloxacin). At the same time, activity against gram-negative bacteria does not decrease. Important property These drugs are active against a number of bacteria resistant to second generation fluoroquinolones. Due to high activity against pathogens bacterial infections VDPs and NDPs are sometimes called “respiratory” fluoroquinolones.

IN varying degrees enterococci are sensitive to fluoroquinolones, Corynebacterium spp., Campylobacter spp., H. pylori, U. urealyticum.

Pharmacokinetics

All quinolones are well absorbed from the gastrointestinal tract. Food may slow the absorption of quinolones but does not significantly affect bioavailability. Maximum concentrations in the blood are achieved on average 1-3 hours after ingestion. The drugs cross the placental barrier and penetrate into the breast milk. They are excreted from the body primarily by the kidneys and create high concentrations in urine. Partially excreted in bile.

First generation quinolones do not create therapeutic concentrations in the blood, organs and tissues. Nalidixic and oxolinic acids undergo intensive biotransformation and are excreted mainly in the form of active and inactive metabolites. Pipemidic acid is little metabolized and is excreted unchanged. The half-life of nalidixic acid is 1-2.5 hours, pipemidic acid - 3-4 hours, oxolinic acid - 6-7 hours. Maximum concentrations in urine are created on average after 3-4 hours.

If renal function is impaired, the elimination of quinolones slows down significantly.

Fluoroquinolones, unlike non-fluorinated quinolones, have a large volume of distribution, create high concentrations in organs and tissues, and penetrate into cells. The exception is norfloxacin, the most high levels which are observed in the intestines, bladder and prostate gland. The highest tissue concentrations are achieved by ofloxacin, levofloxacin, lomefloxacin, sparfloxacin, moxifloxacin. Ciprofloxacin, ofloxacin, levofloxacin and pefloxacin cross the BBB, reaching therapeutic concentrations.

The rate of metabolism depends on physical and chemical properties of the drug: pefloxacin is biotransformed most actively, lomefloxacin, ofloxacin, levofloxacin are the least actively biotransformed. From 3-4% to 15-28% of the dose taken is excreted in feces.

The half-life of various fluoroquinolones ranges from 3-4 hours (norfloxacin) to 12-14 hours (pefloxacin, moxifloxacin) and even up to 18-20 hours (sparfloxacin).

In cases of renal dysfunction, the half-life of ofloxacin, levofloxacin and lomefloxacin is most significantly prolonged. For severe renal failure dose adjustment of all fluoroquinolones is necessary. In case of severe liver dysfunction, a dose adjustment of pefloxacin may be required.

During hemodialysis, fluoroquinolones are removed in small quantities (ofloxacin - 10-30%, other drugs - less than 10%).

Adverse reactions

Common to all quinolones

Gastrointestinal tract: heartburn, pain in the epigastric region, loss of appetite, nausea, vomiting, diarrhea.

CNS: ototoxicity, drowsiness, insomnia, headache, dizziness, visual disturbances, paresthesia, tremor, convulsions.

Allergic reactions: rash, itching, angioedema; photosensitivity (most typical for lomefloxacin and sparfloxacin).

Characteristic of 1st generation quinolones

Hematological reactions: thrombocytopenia, leukopenia; with deficiency of glucose-6-phosphate dehydrogenase - hemolytic anemia.

Liver: cholestatic jaundice, hepatitis.

Characteristic for fluoroquinolones (rare and very rare)

Musculoskeletal system: arthropathy, arthralgia, myalgia, tendinitis, tendovaginitis, tendon rupture.

Kidneys: crystalluria, transient nephritis.

Heart: prolongation of the QT interval on the electrocardiogram.

Other: most often - candidiasis of the oral mucosa and/or vaginal candidiasis, pseudomembranous colitis.

Indications

First generation quinolones

UTI infections: acute cystitis, anti-relapse therapy for chronic forms infections. Should not be used when acute pyelonephritis.

Intestinal infections: shigellosis, bacterial enterocolitis (nalidixic acid).

Fluoroquinolones

URT infections: sinusitis, especially caused by multidrug-resistant strains, malignant otitis externa.

NPD infections: exacerbation chronic bronchitis, community-acquired and nosocomial pneumonia, legionellosis.

Intestinal infections: shigellosis, typhoid fever, generalized salmonellosis, yersiniosis, cholera.

Anthrax.

Intra-abdominal infections.

Infections of the pelvic organs.

UTI infections (cystitis, pyelonephritis).

Prostatitis.

Infections of the skin, soft tissues, bones and joints.

Eye infections.

Meningitis caused by gram-negative microflora (ciprofloxacin).

Bacterial infections in patients with cystic fibrosis.

Neutropenic fever.

Tuberculosis (ciprofloxacin, ofloxacin and lomefloxacin in combination therapy with drug-resistant tuberculosis).

Norfloxacin, taking into account the characteristics of pharmacokinetics, is used only for intestinal infections, urinary tract infections and prostatitis.

Contraindications

For all quinolones

Allergic reaction to drugs of the quinolone group.

Glucose-6-phosphate dehydrogenase deficiency.

Pregnancy.

Additionally for 1st generation quinolones

Severe dysfunction of the liver and kidneys.

Severe cerebral atherosclerosis.

Additionally for all fluoroquinolones

Childhood.

Lactation.

Warnings

Allergy. Cross to all drugs of the quinolone group.

Pregnancy. Reliable clinical data on toxic effect There are no quinolones for the fetus. There are isolated reports of hydrocephalus, increased intracranial pressure and bulging fontanel in newborns whose mothers took nalidixic acid during pregnancy. Due to the experimental development of arthropathy in immature animals, the use of all quinolones during pregnancy is not recommended.

Lactation. Quinolones pass into breast milk in small quantities. There are reports of hemolytic anemia in newborns whose mothers took nalidixic acid during breastfeeding. In experiments, quinolones caused arthropathy in immature animals, therefore, when prescribing them to nursing mothers, it is recommended to transfer the child to artificial feeding.

Pediatrics. Based on experimental data, the use of quinolones is not recommended during the developmental period osteoarticular system. Oxolinic acid is contraindicated in children under 2 years of age, pipemidic acid - up to 1 year, nalidixic acid - up to 3 months.

Fluoroquinolones are not recommended for use in children and adolescents. However, available clinical experience and special studies of the use of fluoroquinolones in pediatrics have not confirmed the risk of damage to the osteoarticular system, and therefore it is permissible to prescribe fluoroquinolones to children for health reasons (exacerbation of infection in cystic fibrosis; severe infections of various localizations caused by multidrug-resistant strains of bacteria; infections in neutropenia).

Geriatrics. In older people, the risk of tendon rupture increases when using fluoroquinolones, especially in combination with glucocorticoids.

Diseases of the central nervous system. Quinolones have a stimulating effect on the central nervous system, so they are not recommended for use in patients with convulsive syndrome in the anamnesis. The risk of developing seizures increases in patients with disorders cerebral circulation, epilepsy and parkinsonism. When using nalidixic acid, intracranial pressure may increase.

Impaired kidney and liver function. First generation quinolones should not be used for renal and liver failure, since due to the accumulation of drugs and their metabolites, the risk of toxic effects increases. Doses of fluoroquinolones in severe renal failure are subject to adjustment.

Acute porphyria. Quinolones should not be used in patients with acute porphyria, since in animal experiments they have a porphyrinogenic effect.

Drug interactions

When used simultaneously with antacids and other drugs containing magnesium, zinc, iron, and bismuth ions, the bioavailability of quinolones may decrease due to the formation of non-absorbable chelate complexes.

Pipemidic acid, ciprofloxacin, norfloxacin and pefloxacin may slow down the elimination of methylxanthines (theophylline, caffeine) and increase the risk of their toxic effects.

The risk of neurotoxic effects of quinolones increases with joint use with NSAIDs, nitroimidazole derivatives and methylxanthines.

Quinolones exhibit antagonism with nitrofuran derivatives, so combinations of these drugs should be avoided.

First generation quinolones, ciprofloxacin and norfloxacin may interfere with metabolism indirect anticoagulants in the liver, which leads to an increase in prothrombin time and the risk of bleeding. With simultaneous use, dose adjustment of the anticoagulant may be necessary.

Fluoroquinolones should be prescribed with caution concomitantly with drugs that prolong the QT interval, as the risk of developing cardiac arrhythmias increases.

When used simultaneously with glucocorticoids, the risk of tendon rupture increases, especially in the elderly.

When using ciprofloxacin, norfloxacin and pefloxacin together with drugs that alkalinize the urine (carbonic anhydrase inhibitors, citrates, sodium bicarbonate), the risk of crystalluria and nephrotoxic effects increases.

When used simultaneously with azlocillin and cimetidine, due to a decrease in tubular secretion, the elimination of fluoroquinolones slows down and their concentrations in the blood increase.

Patient Information

When taken orally, quinolone medications should be taken with a full glass of water. Take at least 2 hours before or 6 hours after taking antacids and preparations of iron, zinc, bismuth.

Strictly follow the regimen and treatment regimens throughout the course of therapy, do not miss a dose and take it at regular intervals. If you miss a dose, take it as soon as possible; do not take if it is almost time for the next dose; do not double the dose. Maintain the duration of therapy.

Do not use drugs with expired suitability.

During the treatment period, maintain sufficient water regime(1.2-1.5 l/day).

Avoid direct exposure to sunlight and ultraviolet rays while using the drugs and for at least 3 days after the end of treatment.

Consult your doctor if improvement does not occur within a few days or if new symptoms appear. If pain occurs in the tendons, you should rest the affected joint and consult a doctor.

Table. Drugs of the quinolone/fluoroquinolone group.
Main characteristics and application features

INN	Lekforma LS	F (inside), %	T ½, h *	Dosage regimen	Features of drugs
First generation quinolones (non-fluorinated)
Nalidixic acid	Caps. 0.5 g Table 0.5 g	96	1-2,5	Inside Adults: 0.5-1.0 g every 6 hours Children over 3 months: 55 mg/kg per day in 4 divided doses	Active only against gram-negative bacteria. Not used for acute pyelonephritis due to low concentrations in kidney tissue. When prescribed for more than 2 weeks, the dose should be reduced by 2 times, kidney function, liver function and blood picture should be monitored
Oxolinic (oxolinic) acid	Table 0.25 g	ND	6-7	Inside Adults: 0.5-0.75 g every 12 hours Children over 2 years: 0.25 g every 12 hours	- variable absorption in the gastrointestinal tract; - longer T ½; - worse tolerated
Pipemidic (pipemidic) acid	Caps. 0.2 g; 0.4 g Table 0.4 g	80-90	3-4	Inside Adults: 0.4 g every 12 hours Children over 1 year: 15 mg/kg/day in 2 divided doses	Differences from nalidixic acid: - wider range; - longer T ½
Quinolones II - IV generations (fluoroquinolones)
Ciprofloxacin	Table 0.25 g; 0.5 g; 0.75 g; 0.1 g R-r d/inf. 0.1 and 0.2 g per bottle. 50 ml and 100 ml Conc. d/inf. 0.1 g per amp. 10 ml each Eye/ear cap. 0.3% Eye. ointment 0.3%	70-80	4-6	Inside Adults: 0.25-0.75 g every 12 hours; within 3 days; for acute gonorrhea - 0.5 g once IV Adults: 0.4-0.6 g every 12 hours Locally Eye. cap. instill 1-2 drops. into the affected eye every 4 hours, in severe cases - every hour until improvement	The most active fluoroquinolone against most gram-negative bacteria Superior to other fluoroquinolones in activity against P. aeruginosa Used in combination therapy of drug-resistant forms of tuberculosis
Ofloxacin	Table 0.1 g; 0.2 g R-r d/inf. 2 mg/ml per vial. Eye/ear cap. 0.3% Eye. ointment 0,3 %	95-100	4,5-7	Inside at acute cystitis in women - 0.1 g every 12 hours within 3 days; for acute gonorrhea - 0.4 g once IV Adults: 0.2-0.4 g/day in 1-2 administrations Administered by slow infusion over 1 hour Locally Ears cap. instill 2-3 drops. into the affected ear 4-6 times a day, in severe cases - every 2-3 hours, gradually reducing as it improves Eye. the ointment is placed behind the lower eyelid of the affected eye 3-5 times a day	The most active fluoroquinolone of the second generation against chlamydia and pneumococci. Has little effect on the metabolism of methylxanthines and indirect anticoagulants. Used as part of combination therapy drug-resistant forms of tuberculosis
Pefloxacin	Table 0.2 g; 0.4 g R-r d/in. 0.4 g per amp. 5 ml each R-r d/in. IV 4 mg/ml in vial. 100 ml each	95-100	8-13	Inside Adults: 0.8 g for the first dose, then 0.4 g every 12 hours; for acute cystitis in women and for acute gonorrhea - 0.8 g once IV Adults: 0.8 g for the first administration, then 0.4 g every 12 hours Administered by slow infusion over 1 hour	Slightly less active in vitro ciprofloxacin, ofloxacin, levofloxacin. It penetrates the BBB better than other fluoroquinolones. Forms an active metabolite - norfloxacin
Norfloxacin	Table 0.2 g; 0.4 g; 0.8 g Eye/ear cap. 0.3% per bottle. 5 ml each	30-70	3-4	Inside Adults: 0.2-0.4 g every 12 hours; for acute cystitis in women - 0.4 g every 12 hours within 3 days; for acute gonorrhea - 0.8 g once Locally Eye. cap. instill 1-2 drops. into the affected eye every 4 hours, in severe cases - every hour until improvement. Ears cap. instill 2-3 drops. into the affected ear 4-6 times a day, in severe cases - every 2-3 hours, gradually reducing as it improves	Systemically used only for the treatment of UTI infections, prostatitis, gonorrhea and intestinal infections(shigellosis). Locally - for infections of the eyes and outer ear
Lomefloxacin	Table 0.4 g Eye. cap. 0.3% per bottle. 5 ml each	95-100	7-8	Inside Adults: 0.4-0.8 g/day in 1-2 doses Locally Eye. cap. instill 1-2 drops. into the affected eye every 4 hours, in severe cases - every hour until improvement	Inactive against pneumococcus, chlamydia, mycoplasma. Used as part of combination therapy for drug-resistant forms of tuberculosis. More often than other fluoroquinolones, it causes photodermatitis. Does not interact with methylxanthines and indirect anticoagulants
Sparfloxacin	Table 0.2 g	60	18-20	Inside Adults: on the first day 0.4-0.2 g in one dose, on subsequent days 0.1-0.2 g 1 time per day	The spectrum of activity is close to levofloxacin. Highly active against mycobacteria. Surpasses other fluoroquinolones in terms of duration of action. More often than other fluoroquinolones, it causes photodermatitis. Does not interact with methylxanthines.
Levofloxacin	Table 0.25 g; 0.5 g R-r d/inf. 5 mg/ml per bottle. By 100 ml	99	6-8	Inside Adults: 0.25-0.5 g every 12-24 hours; at acute sinusitis- 0.5 g 1 time per day; for pneumonia and severe forms infections - 0.5 g every 12 hours IV Adults: 0.25-0.5 g every 12-24 hours, for severe forms 0.5 g every 12 hours Administered by slow infusion over 1 hour	Levorotatory isomer ofloxacin. Twice as active in vitro than ofloxacin, including against gram-positive bacteria, chlamydia, mycoplasmas and mycobacteria. Better tolerated than ofloxacin
Moxifloxacin	Table 0.4 g	90	12	Inside Adults: 0.4 g once per day	Superior to other fluoroquinolones in activity against pneumococci, including multidrug-resistant ones; chlamydia, mycoplasma, anaerobes. Does not interact with methylxanthines

* At normal function kidney

MOXIFLOXACIN
A new antimicrobial drug from the group of fluoroquinolones

Antimicrobial drugs of the quinolone group include a large number of substances that are derivatives of similar chemical structure naphthyridine and quinoline (in the naphthyridine molecule the nitrogen atom is replaced by a carbon atom in position 8 of the naphthyridine ring, Fig. 1).

The first quinolone drug was nalidixic acid, synthesized in 1962 from naphthyridine. The drug has a limited spectrum of antimicrobial action with activity against some gram-negative bacteria, mainly enterobacteria. The pharmacokinetics of nalidixic acid is characterized by low concentrations of the drug in the blood serum, poor penetration into organs, tissues and cells of the macroorganism; the drug is found in high concentrations in urine and intestinal contents. There was a rapid development of microbial resistance to the drug. These properties of nalidixic acid have determined its rather limited use, mainly in the treatment of infections. urinary tract and some intestinal infections. Further searches in the series of quinolones led to the creation of a number of antimicrobial drugs, the properties of which were not fundamentally different from nalidixic acid, and the rapid development of resistance to them in clinical strains of microorganisms limited their use, although a number of drugs are still used to this day (for example, oxolinic acid, pipemidic acid ).

Further searches in the series of quinolones led to the production of a number of compounds with fundamentally new properties. This was achieved by introducing a fluorine atom into the quinoline or naphthyridine molecule, and only at position 6 (Fig. 1). The synthesized compounds were called “fluoroquinolones”. The first drug of the fluoroquinolone group was flumequine. The drugs created on the basis of synthesized fluorinated quinolones received wide application in the clinic for cookies bacterial infections of different origins and localization.

Rice. 1.
Structural formula quinoline and naphthyridine (A) and their fluorinated derivatives (B)

Rice. 2.
Structural formula of fluoroquinolones

The molecule of each quinolone class compound contains a six-membered ring with a COOH group at position 3 and a keto group (C=O) at position 4 - a pyridone fragment (Fig. 2), which determines the main mechanism of action of quinolones - inhibition of DNA gyrase and, accordingly, antimicrobial activity. Based on this chemical feature The molecules of these compounds are sometimes called "4-quinolones". Chemical compounds similar to quinolones that do not have a pyridone fragment and a keto group in position 4 in the molecule do not inhibit DNA gyrase. Intensity of DNA gyrase inhibition, breadth of the antimicrobial spectrum, pharmacokinetic properties individual drugs depend on the general structure of the molecule and the nature of the radicals at any position in the cycle.

Regardless of the presence (or absence) of a fluorine atom, all chemical compounds of the quinolone class have a single mechanism of action on the microbial cell - inhibition of the key bacterial enzyme - DNA gyrase, which determines the process of DNA biosynthesis and cell division. Based on the same mechanism of antimicrobial action, quinolones and fluoroquinolones received the general name “DNA gyrase inhibitors.”

As noted above, the main chemical difference between fluoroquinolones and quinolones is the presence of a fluorine atom at position 6 of the molecule. It has been shown that the introduction of another substituent instead of fluorine (another halogen, alkyl radical, etc.) reduces the severity of the antimicrobial effect. Attempts to introduce additional fluorine atoms (di- and trifluoroquinolones) did not lead to fundamental changes in the activity of the compounds, but made it possible to modify a number of properties (increased activity against certain groups of microorganisms, changes in pharmacokinetic properties).

Despite the similarities chemical structure non-fluorinated and fluorinated quinolones, they differ significantly in their properties (Table 1). These differences in properties give reason to consider fluoroquinolones as an independent group of drugs within the quinolone class.

Currently, the range of fluoroquinolones includes about 20 drugs. The main fluoroquinolones that have found clinical use are presented in Table. 2.

Table 1.
Comparative characteristics fluorinated and non-fluorinated quinolones

Fluoroquinolones	Non-fluorinated quinolones
Wide antimicrobial spectrum: gram-positive and gram-negative aerobic and anaerobic bacteria, mycobacteria, mycoplasma, chlamydia, rickettsia, borrelia	Limited antimicrobial spectrum: preferential activity against Enterobacteriaceae
Pronounced post-antibiotic effect	Post-antibiotic effect is weak or absent
High bioavailability when taken orally	Low bioavailability when taken orally
Good pharmacokinetic properties: rapid absorption from gastrointestinal tract, long stay in the body, good penetration into organs, tissues and cells, elimination by renal and extrarenal routes	Low serum concentrations, poor penetration into organs, tissues and cells; high concentrations in urine and feces
Oral and parenteral use	Use only internally
Wide indications for use: bacterial infections of various localizations, chlamydia, mycobacteriosis, rickettsiosis, borrelia Systemic action for generalized infections	Limited indications for use: urinary tract infections, some intestinal infections (dysentery, enterocolitis). Lack of systemic effect in generalized infections
	Relatively low toxicity
	Well tolerated by patients
	Arthrotoxicity in experiments for immature animals at certain age periods
Use in adult patients; restrictions for use in pediatrics (during the period of growth and formation of the osteoarticular system) based on experimental data	Use in adult patients and in pediatrics (despite data on arthrotoxicity in the experiment)

Not all drugs are equally widely used in the clinic. The most widely used are ciprofloxacin, ofloxacin, pefloxacin, norfloxacin, and lomefloxacin. All of them are registered in Russia. In addition to these drugs, enoxacin, sparfloxacin, grepafloxacin, trovafloxacin, sparfloxacin, levofloxacin, and moxifloxacin were registered in Russia. It should be noted that due to side effects, revealed after successful implementation extensive cross-national, multi-center (in many cases controlled) trials, some drugs (temafloxacin, grepafloxacin, trovafloxacin, clinafloxacin) were recalled by manufacturers with pharmaceutical market or significant restrictions have been introduced on their use.

Drugs of the quinolone class, used in clinical practice since the early 60s, are fundamentally different in their mechanism of action from other AMPs, which ensures their activity against resistant, including multiresistant, strains of microorganisms. The class of quinolones includes two main groups of drugs that differ fundamentally in structure, activity, pharmacokinetics and breadth of indications for use: non-fluorinated quinolones and fluoroquinolones. Quinolones are classified according to the time when new drugs with improved antimicrobial properties were introduced into practice. According to the working classification proposed by R. Quintiliani (1999), quinolones are divided into four generations:

Classification of quinolones

I generation:

Nalidixic acid

Oxolinic acid

Pipemidic (pipemidic) acid

II generation:

Lomefloxacin

Norfloxacin

Ofloxacin

Pefloxacin

Ciprofloxacin

III generation:

Levofloxacin
Sparfloxacin

IV generation:

Moxifloxacin

The listed drugs are registered in Russia. Some other drugs of the quinolone class are also used abroad, mainly fluoroquinolones.

First generation quinolones are predominantly active against gram-negative flora and do not create high concentrations in the blood and tissues.

Fluoroquinolones, approved for clinical use since the early 80s (II generation), are distinguished by a wide spectrum of antimicrobial action, including staphylococci, high bactericidal activity and good pharmacokinetics, which allows their use for the treatment of infections of various localizations. Fluoroquinolones, introduced into practice since the mid-90s (III-IV generation), are characterized by higher activity against gram-positive bacteria (primarily pneumococci), intracellular pathogens, anaerobes (IV generation), as well as even more optimized pharmacokinetics. The presence of dosage forms for intravenous administration and oral administration in a number of drugs, combined with high bioavailability, allows for stepwise therapy, which, with comparable clinical effectiveness, is significantly cheaper than parenteral therapy.

The high bactericidal activity of fluoroquinolones has made it possible to develop dosage forms for topical use in the form of eye and ear drops for a number of drugs (ciprofloxacin, ofloxacin, lomefloxacin, norfloxacin).

Mechanism of action

Quinolones have a bactericidal effect. By inhibiting two vital enzymes of the microbial cell - DNA gyrase and topoisomerase IV, they disrupt DNA synthesis.

Activity spectrum

Fluoroquinolones have a much wider spectrum. They are active against a number of gram-positive aerobic bacteria ( Staphylococcus spp.), most gram-negative strains, including E.coli(including enterotoxigenic strains), Shigella spp., Salmonella spp., Enterobacter spp., Klebsiella spp., Proteus spp., Serratia spp., Providencia spp., Citrobacter spp., M. morganii, Vibrio spp., Haemophilus spp., Neisseria spp., Pasteurella spp., Pseudomonas spp., Legionella spp., Brucella spp., Listeria spp.

In addition, fluoroquinolones are usually active against bacteria resistant to first generation quinolones. Fluoroquinolones of the third and, especially, fourth generation are highly active against pneumococci, more active than drugs of the second generation against intracellular pathogens ( Chlamydia spp., Mycoplasma spp., M. tuberculosis, fast-growing atypical mycobacteria ( M.avium etc.), anaerobic bacteria (moxifloxacin). At the same time, activity against gram-negative bacteria does not decrease. An important property of these drugs is their activity against a number of bacteria resistant to second generation fluoroquinolones. Due to their high activity against the causative agents of bacterial infections UDP and NDP, they are sometimes called “respiratory” fluoroquinolones.

Enterococci are sensitive to fluoroquinolones to varying degrees. Corynebacterium spp., Campylobacter spp., H. pylori, U. urealyticum.

Pharmacokinetics

All quinolones are well absorbed from the gastrointestinal tract. Food may slow the absorption of quinolones but does not significantly affect bioavailability. Maximum concentrations in the blood are achieved on average 1-3 hours after oral administration. The drugs cross the placental barrier and pass into breast milk in small quantities. They are excreted primarily by the kidneys and create high concentrations in the urine. Partially excreted in bile.

If renal function is impaired, the elimination of quinolones slows down significantly.

Fluoroquinolones, unlike non-fluorinated quinolones, have a large volume of distribution, create high concentrations in organs and tissues, and penetrate into cells. The exception is norfloxacin, the highest levels of which are observed in the intestines, urinary tract and prostate gland. The highest tissue concentrations are achieved by ofloxacin, levofloxacin, lomefloxacin, sparfloxacin, moxifloxacin. Ciprofloxacin, ofloxacin, levofloxacin and pefloxacin cross the BBB, reaching therapeutic concentrations.

The degree of metabolism depends on the physicochemical properties of the drug: pefloxacin is biotransformed most actively, lomefloxacin, ofloxacin, levofloxacin are least actively biotransformed. From 3-4% to 15-28% of the dose taken is excreted in feces.

Bacterial infections in patients with cystic fibrosis.

Tuberculosis (ciprofloxacin, ofloxacin and lomefloxacin in combination therapy for drug-resistant tuberculosis).

Norfloxacin, taking into account the characteristics of pharmacokinetics, is used only for intestinal infections, urinary tract infections and prostatitis.

Contraindications

For all quinolones

Allergic reaction to drugs of the quinolone group.

Glucose-6-phosphate dehydrogenase deficiency.

Pregnancy.

Additionally for 1st generation quinolones

Severe dysfunction of the liver and kidneys.

Severe cerebral atherosclerosis.

Additionally for all fluoroquinolones

Childhood.

Lactation.

Warnings

Allergy. Cross to all drugs of the quinolone group.

Pregnancy. There are no reliable clinical data on the toxic effects of quinolones on the fetus. There are isolated reports of hydrocephalus, increased intracranial pressure and bulging fontanel in newborns whose mothers took nalidixic acid during pregnancy. Due to the experimental development of arthropathy in immature animals, the use of all quinolones during pregnancy is not recommended.

Lactation. Quinolones pass into breast milk in small quantities. There are reports of hemolytic anemia in newborns whose mothers took nalidixic acid during breastfeeding. In experiments, quinolones caused arthropathy in immature animals, therefore, when prescribing them to nursing mothers, it is recommended to transfer the child to artificial feeding.

Pediatrics. Based on experimental data, the use of quinolones is not recommended during the formation of the osteoarticular system. Oxolinic acid is contraindicated in children under 2 years of age, pipemidic acid - up to 1 year, nalidixic acid - up to 3 months.

Fluoroquinolones are not recommended for use in children and adolescents. However, existing clinical experience and special studies of the use of fluoroquinolones in pediatrics have not confirmed the risk of damage to the osteoarticular system, and therefore it is permissible to prescribe fluoroquinolones to children for health reasons (exacerbation of infection in cystic fibrosis; severe infections of various localizations caused by multidrug-resistant strains of bacteria; infections in neutropenia ).

Geriatrics. In older people, the risk of tendon rupture increases when using fluoroquinolones, especially in combination with glucocorticoids.

Diseases of the central nervous system. Quinolones have a stimulating effect on the central nervous system, so they are not recommended for use in patients with a history of seizures. The risk of developing seizures increases in patients with cerebrovascular accidents, epilepsy and parkinsonism. When using nalidixic acid, intracranial pressure may increase.

Impaired kidney and liver function. First generation quinolones should not be used in cases of renal and liver failure, since the risk of toxic effects increases due to the accumulation of drugs and their metabolites. Doses of fluoroquinolones in severe renal failure are subject to adjustment.

Acute porphyria. Quinolones should not be used in patients with acute porphyria, since in animal experiments they have a porphyrinogenic effect.

Drug interactions

Pipemidic acid, ciprofloxacin, norfloxacin and pefloxacin may slow down the elimination of methylxanthines (theophylline, caffeine) and increase the risk of their toxic effects.

The risk of neurotoxic effects of quinolones increases when combined with NSAIDs, nitroimidazole derivatives and methylxanthines.

Quinolones exhibit antagonism with nitrofuran derivatives, so combinations of these drugs should be avoided.

First generation quinolones, ciprofloxacin and norfloxacin can interfere with the metabolism of indirect anticoagulants in the liver, which leads to an increase in prothrombin time and the risk of bleeding. With simultaneous use, dose adjustment of the anticoagulant may be necessary.

Fluoroquinolones should be prescribed with caution concomitantly with drugs that prolong the QT interval, as the risk of developing cardiac arrhythmias increases.

When used simultaneously with glucocorticoids, the risk of tendon rupture increases, especially in the elderly.

When used simultaneously with azlocillin and cimetidine, due to a decrease in tubular secretion, the elimination of fluoroquinolones slows down and their concentrations in the blood increase.

Patient Information

When taken orally, quinolone medications should be taken with a full glass of water. Take at least 2 hours before or 6 hours after taking antacids and preparations of iron, zinc, bismuth.

Do not use drugs that have expired.

During the treatment period, maintain sufficient water regime (1.2-1.5 l/day).

Avoid direct exposure to sunlight and ultraviolet rays while using the drugs and for at least 3 days after the end of treatment.

Consult your doctor if improvement does not occur within a few days or if new symptoms appear. If pain occurs in the tendons, you should rest the affected joint and consult a doctor.

Table. Drugs of the quinolone/fluoroquinolone group.
Main characteristics and application features

INN	Lekforma LS	F (inside), %	T ½, h *	Dosage regimen	Features of drugs
First generation quinolones (non-fluorinated)
Nalidixic acid	Caps. 0.5 g Table 0.5 g	96	1-2,5	Inside Adults: 0.5-1.0 g every 6 hours Children over 3 months: 55 mg/kg per day in 4 divided doses	Active only against gram-negative bacteria. Not used for acute pyelonephritis due to low concentrations in kidney tissue. When prescribed for more than 2 weeks, the dose should be reduced by 2 times, kidney function, liver function and blood picture should be monitored
Oxolinic (oxolinic) acid	Table 0.25 g	ND	6-7	Inside Adults: 0.5-0.75 g every 12 hours Children over 2 years: 0.25 g every 12 hours	- variable absorption in the gastrointestinal tract; - longer T ½; - worse tolerated
Pipemidic (pipemidic) acid	Caps. 0.2 g; 0.4 g Table 0.4 g	80-90	3-4	Inside Adults: 0.4 g every 12 hours Children over 1 year: 15 mg/kg/day in 2 divided doses	Differences from nalidixic acid: - wider range; - longer T ½
Quinolones II - IV generations (fluoroquinolones)
Ciprofloxacin	Table 0.25 g; 0.5 g; 0.75 g; 0.1 g R-r d/inf. 0.1 and 0.2 g per bottle. 50 ml and 100 ml Conc. d/inf. 0.1 g per amp. 10 ml each Eye/ear cap. 0.3% Eye. ointment 0.3%	70-80	4-6	Inside Adults: 0.25-0.75 g every 12 hours; within 3 days; for acute gonorrhea - 0.5 g once IV Adults: 0.4-0.6 g every 12 hours Locally Eye. cap. instill 1-2 drops. into the affected eye every 4 hours, in severe cases - every hour until improvement	The most active fluoroquinolone against most gram-negative bacteria Superior to other fluoroquinolones in activity against P. aeruginosa Used in combination therapy of drug-resistant forms of tuberculosis
Ofloxacin	Table 0.1 g; 0.2 g R-r d/inf. 2 mg/ml per vial. Eye/ear cap. 0.3% Eye. ointment 0,3 %	95-100	4,5-7	Inside for acute cystitis in women - 0.1 g every 12 hours within 3 days; for acute gonorrhea - 0.4 g once IV Adults: 0.2-0.4 g/day in 1-2 administrations Administered by slow infusion over 1 hour Locally Ears cap. instill 2-3 drops. into the affected ear 4-6 times a day, in severe cases - every 2-3 hours, gradually reducing as it improves Eye. the ointment is placed behind the lower eyelid of the affected eye 3-5 times a day	The most active fluoroquinolone of the second generation against chlamydia and pneumococci. Has little effect on the metabolism of methylxanthines and indirect anticoagulants. Used as part of combination therapy drug-resistant forms of tuberculosis
Pefloxacin	Table 0.2 g; 0.4 g R-r d/in. 0.4 g per amp. 5 ml each R-r d/in. IV 4 mg/ml in vial. 100 ml each	95-100	8-13	Inside Adults: 0.8 g for the first dose, then 0.4 g every 12 hours; for acute cystitis in women and for acute gonorrhea - 0.8 g once IV Adults: 0.8 g for the first administration, then 0.4 g every 12 hours Administered by slow infusion over 1 hour	Slightly less active in vitro ciprofloxacin, ofloxacin, levofloxacin. It penetrates the BBB better than other fluoroquinolones. Forms an active metabolite - norfloxacin
Norfloxacin	Table 0.2 g; 0.4 g; 0.8 g Eye/ear cap. 0.3% per bottle. 5 ml each	30-70	3-4	Inside Adults: 0.2-0.4 g every 12 hours; for acute cystitis in women - 0.4 g every 12 hours within 3 days; for acute gonorrhea - 0.8 g once Locally Eye. cap. instill 1-2 drops. into the affected eye every 4 hours, in severe cases - every hour until improvement. Ears cap. instill 2-3 drops. into the affected ear 4-6 times a day, in severe cases - every 2-3 hours, gradually reducing as it improves	Systemically used only for the treatment of UTI infections, prostatitis, gonorrhea and intestinal infections (shigellosis). Locally - for infections of the eyes and outer ear
Lomefloxacin	Table 0.4 g Eye. cap. 0.3% per bottle. 5 ml each	95-100	7-8	Inside Adults: 0.4-0.8 g/day in 1-2 doses Locally Eye. cap. instill 1-2 drops. into the affected eye every 4 hours, in severe cases - every hour until improvement	Inactive against pneumococcus, chlamydia, mycoplasma. Used as part of combination therapy for drug-resistant forms of tuberculosis. More often than other fluoroquinolones, it causes photodermatitis. Does not interact with methylxanthines and indirect anticoagulants
Sparfloxacin	Table 0.2 g	60	18-20	Inside Adults: on the first day 0.4-0.2 g in one dose, on subsequent days 0.1-0.2 g 1 time per day	The spectrum of activity is close to levofloxacin. Highly active against mycobacteria. Surpasses other fluoroquinolones in terms of duration of action. More often than other fluoroquinolones, it causes photodermatitis. Does not interact with methylxanthines.
Levofloxacin	Table 0.25 g; 0.5 g R-r d/inf. 5 mg/ml per bottle. By 100 ml	99	6-8	Inside Adults: 0.25-0.5 g every 12-24 hours; for acute sinusitis - 0.5 g 1 time per day; for pneumonia and severe forms of infections - 0.5 g every 12 hours IV Adults: 0.25-0.5 g every 12-24 hours, for severe forms 0.5 g every 12 hours Administered by slow infusion over 1 hour	Levorotatory isomer of ofloxacin. Twice as active in vitro than ofloxacin, including against gram-positive bacteria, chlamydia, mycoplasmas and mycobacteria. Better tolerated than ofloxacin
Moxifloxacin	Table 0.4 g	90	12	Inside Adults: 0.4 g once per day	Superior to other fluoroquinolones in activity against pneumococci, including multidrug-resistant ones; chlamydia, mycoplasma, anaerobes. Does not interact with methylxanthines

* With normal kidney function

Fluoroquinolones

V. P. Vereitinova, Ph.D. honey. Sciences, O. A. Tarasenko, ass., L. N. Grishchenko
National Pharmaceutical Academy of Ukraine

The quinolone group is a large group of antibacterial drugs that have a similar mechanism of action: inhibition of bacterial DNA synthesis.

The founder of this group was nalidixic acid, synthesized in 1962. In subsequent years, drugs such as oxolinic, pipimediic and pyromidic acids, as well as cinoxacin, were created.

However, due to the pharmacokinetics of these drugs (they are quickly metabolized and quickly excreted, which prevents the development system effects), spectrum of antibacterial action (Gram-negative enterobacteria), the scope of use of these drugs is limited to the treatment of urinary tract infections. These features of the drugs and the rapidly developing resistance of bacteria did not allow the first quinolones to occupy worthy place among antibacterial drugs.

A literally revolutionary revolution in the further development of the described group was made by the idea of incorporating fluorine atoms into the 6th position of the quinoline molecule. This radically changed the spectrum of antibacterial action towards its significant expansion and all the clinical and pharmacological indicators of the new generation of fluorinated derivatives.

Depending on the number of fluorine atoms included in the quinolone molecule, monofluorinated compounds (ciprofloxacin, norfloxacin, ofloxacin, pefloxacin, rufloxacin, enoxacin), di- (lomefloxacin, sparfloxacin) and trifluorinated compounds (fleroxacin, tosufloxacin) are distinguished. In accordance with the stages of development, 4 generations of quinolones/fluoroquinolones are distinguished (Table 1)

The first drugs of the fluoroquinolone group were proposed for clinical practice in 1978–1980. To date, more than 30 drugs have been developed and more than 20 of them have been studied in detail in the clinic. Over 20 years of clinical use, fluoroquinolones have taken one of the leading places among antimicrobial agents. Moreover, they are considered as a serious alternative to highly active antibiotics wide range actions in the treatment of severe infections of various localizations. The drugs owe this rise in popularity to their high bioavailability when taken orally, ultra-wide spectrum of antibacterial action, bactericidal effect, good pharmacokinetic properties, tolerability and originality of the mechanism of action. The most studied and widely used in the clinic are monofluorinated compounds.

All quinolones selectively inhibit one of the key enzymes of the microbial cell - DNA gyrase, which is responsible for the normal biosynthesis and replication of bacterial DNA.

Fluoroquinolones are broad-spectrum drugs active against gram-positive and gram-negative, aerobic and anaerobic microorganisms, chlamydia, mycoplasma, legionella, mycobacteria. Fungi, viruses, treponemes, and most protozoa are resistant to fluoroquinolones. However, despite all the similarities in the antibacterial spectrum, there are differences in the sensitivity of microorganisms both to representatives of different generations of fluoroquinolones, and to certain drugs within a generation (Tables 2, 3, 4, 5, 6).

table 2

In vitro activity of some fluoroquinolones (MIC90, mg/l) against clinical strains of gram-positive bacteria

Microorganism	Moxifloxacin	Ciprofloxacin	Ofloxacin	Pefloxacin	Lomefloxacin	Trovafloxacin	Grepafloxacin
Staphylococcus aureus MS	0,06	0,5	0,52	0,5-0,1	2	0,03-0,06	<0,125
Staphylococcus aureus MR	2-4	3-64	0,5-16	16	6,25	2-4	0,25-16
Staphylococcus epidermidis MS	0,13	1	0,25-1	1	2	0,03-0,06	0,25
Staphylococcus epidermidis MR	0,13	1	0,5-16	-	-	0,06	8
Streptococcus pneumoniae	0,12-0,25	1-4	2	8	16	0,125	<0,5
Streptococcus pyogenes	0,25	1	2	16	16	0,25	0,25
Enterococcus faecalis	1-4	2-32	2-8	4-8	8	1-2	0,5-4
Enterococcus faecium	4	4-16	8-16	-	-	2	8
Listeria monocytogenes	0,5	1	2-5	8	8	0,25-0,5	-

Note
MS - methicillin-sensitive strains;
MR - methicillin-resistant strains.

1 One of the main methods for microbiological testing of the sensitivity of pathogens to antibacterial agents is the determination of the minimum inhibitory concentration (MIC) of a drug against a specific microorganism. Traditionally, the minimum inhibitory concentration of an antibacterial agent is determined at which the growth of 90% of pathogen strains is suppressed in vitro (MIC90). The lower the MIC value, the more active the drug.

Table 3

In vitro activity of some fluoroquinolones (MIC90, mg/l) against clinical strains of gram-negative bacteria

Microorganism	Moxifloxacin	Ciprofloxacin	Ofloxacin	Pefloxacin	Lomefloxacin	Trovafloxacin	Grepafloxacin
Neisseriaceae
Neisseria gonorrhoeae AMP-S	0,016	0,002-0,12	0,03-0,06	0,06	<0,25	0,03	<0,01
Neisseria meningitidis	0,015	0,004-0,12	0,015-0,06	0,03	<0,25	0,004-0,12	<0,01
Enterobacteriaceae
Escherichia coli AMP-S	0,008	0,016	0,06-0,125	<0,125	0,5	0,03-0,06	<0,125
Klebsiella pneumoniae CAZ-S	0,13	0,06	0,25-0,5	2	2	0,06-11,25	0,25
Proteus mirabilis	0,25	0,06-0,25	0,125-0,5	0,5-1	1	0,25	0,25-0,5
Proteus vulgaris	0,5	0,06	0,25-0,5	0,25	0,5	0,25	0,125-0,5
Morganella morganii	0,13-0,25	0,03	0,25-0,5	0,5	5	0,25-2	0,25-0,5
Providencia rettgeri	0,5	0,12	1-2	0,25-0,5	2	0,5	0,5-2
Serratia marcescens	0,25-8	0,25-4	1-4	8	-	0,5-4	1-4
Enterobacter cloacae	0,06	0,03	0,25	0,25	-	0,06-11,125	0,5
Citrobacter freundii	1	0,4	0,25-1	0,5-4	-	0,25-0,5	0,5-1
Salmonella spp.	0,06-0,13	0,03	0,06-0,125	0,125-0,25	0,25	<0,03	0,125
Shigella spp.	0,03	0,01	0,125	0,125-0,25	0,25-1	0,06-0,15	0,03-0,125
Yersinia enterocolitica	0,06	0,1	0,125	0,25	0,25	0,03-0,06	0,25
Other aerobic gram-negative
Haemophilus influenzae AMP-S	0,06	0,008-0,06	0,03-0,06	0,03-0,125	<0,25	<0,03	<0,06
Moraxella catarrhalis	0,06	<0,03-0,25	0,06-0,125	0,25	<0,25	0,06	>0,06
Acinetobacter baumannii	0,03-0,25	0,13-1	0,5-16	1	4-8	8	16
Acinetobacter calcoaceticus	0,06-0,25	0,03-0,25	0,5-16	1	4-8	8	16
Pseudomonas aeruginosa	8->32	1-8	2-16	4-16	8-16	1-2	1-8
Burkholderia cepacia	>128	>128	4-16	-	1,56-4	0,25	0,52
Campylobacter spp.	0,5	0,12-1	0,25	1,5-2	1,56-4	-	-

Note
AMP-S - ampicillin-sensitive strains;
CAZ-S - ceftazidime-sensitive strains;

Table 4

Activity of moxifloxacin and ciprofloxacin in vitro (MIC90, mg/l) against clinical strains of anaerobic bacteria

Microorganism	Moxifloxacin	Ciprofloxacin
Bacteroides fragilis	0,25-2	8
Bacteroides spp.	2-4	8-16
Fusobacterium spp.	0,25-1	2-4
Prevotella spp.	0,5-2	2
Veillonella parvula	0,25	1-4
Actinomyces spp.	0,2	0,5
Clostridium perfringens	0,5	1-2
Clostridium spp.	0,25-1	2
Clostridium difficile	2	32
Peptostreptococcus spp.	0,12-2	0,5-8
Propionibacterium acnes	0,25	-

Table 5

Activity of fluoroquinolones in vitro (MIC90, mg/l) against atypical intracellular microorganisms

Microorganism	Moxifloxacin	Ofloxacin	Pefloxacin	Lomefloxacin
Clamydia pneumoniae	0,06	1	-	-
Clamydia trachomatis	0,06-0,12	2	-	2-4
Chlamydia psittaci	0,06	1-2	-	-
Mycoplasma pneumoniae	0,12	1	-	8
Mycoplasma hominis	0,06	0,5	4	2-8
Ureaplasma urealyticum	0,25	4	4	8
Legionella pneumophila	0,06	0,05	-	1-2

Table 6

In vitro activity of moxifloxacin and other fluoroquinolones (MIC90, mg/l) against mycobacteria

Microorganism	Moxifloxacin	Ofloxacin	Levofloxacin	Sparfloxacin	Lomefloxacin	Ciprofloxacin
Mycobacterium tuberculosis	0,25	0,5-1	0,25	0,06-0,5	2	0,25-0,2
Mycobacterium tuberculosis M-Res	0,5	-	0,25	0,125	-	-
Mycobacterium avium-intracellulare	1-4	2-16	8	1-8	8	18
Mycobacterium kansasii	0,06-0,125	0,5-2	4	0,12-2	0,5	-

Note.
M-Res - multi-resistant strains

As mentioned above, the spectrum of action of first generation quinolones is limited to the effect on some gram-negative microorganisms of the Enterobacteriaceae family. The second generation of quinolones (early fluoroquinolones) significantly increased activity against a wide range of gram-negative aerobic microorganisms, including multidrug-resistant ones, as well as Staphylococcus aureus. Ciprofloxacin, ofloxacin and lomefloxacin inhibit the growth of Mycobacterium tuberculosis. The disadvantage of second generation drugs is their low activity against pneumococci, chlamydia, mycoplasmas and anaerobes.

Since their introduction into the clinic and to the present day, the leading position is occupied by four monofluorinated representatives of the second generation of fluoroquinolones: ciprofloxacin, ofloxacin, pefloxacin and norfloxacin. The great advantage of the first three drugs is that they have two dosage forms - for oral administration and for intravenous administration. The difluoroquinolone lomefloxacin is also a fairly widely used second-generation drug.

Ciprofloxacin (ciprobay, cyprinol) is otherwise called the “gold standard” of fluoroquinolones.

Among fluoroquinolones of all generations, it exhibits the highest in vitro activity against gram-negative microorganisms, including Pseudomonas aeruginosa.

Pefloxacin (abactal) is highly active against most representatives of Enterobacteriaceae, gram-negative cocci, as well as intracellular microorganisms - mycoplasmas, legionella.

Ofloxacin (Tarivid) is close in spectrum and strength of antimicrobial action to ciprofloxacin, but it has higher activity against Staphylococcus aureus and better pharmacokinetic parameters.

Lomefloxacin (maxaquin) is a difluoroquinolone that has an additional fluorine atom in position 8 of the quinolone ring and a 3-methylpiperazinyl radical in position 7. This structure of the drug did not make any noticeable adjustments to the spectrum of action, but optimized its pharmacokinetic properties and ensured the stability of the molecule to biotransformation in the body and practically eliminated unwanted interactions of lomefloxacin with some other drugs. Lomefloxacin is somewhat inferior in antimicrobial effect to ciprofloxacin, but exceeds the activity of ofloxacin. The drug is moderately active against staphylococci and has virtually no effect on streptococci, including pneumococci, mycoplasma, ureaplasma and enterococci. The drug has a pronounced post-antibiotic effect.

In attempts to expand the spectrum of antimicrobial action of fluoroquinolones in the development of new drugs, research was carried out both in terms of synthesis and in terms of modification of the chemical structure of compounds through additional fluorination and the introduction of additional substituents. At the same time, the most important groups in the fluoroquinolone molecule responsible for their antimicrobial properties are those occupying positions 1, 5, 7, 8. The result of scientific research was the creation of fluoroquinolones of the III and IV generations, the antibacterial effect of which against gram-negative microorganisms is not inferior to the action of drugs II generation (except for Pseudomonas aeruginosa). As for gram-positive flora (including pneumococci), as well as chlamydia, mycoplasmas, mycobacteria, in this case the new fluoroquinolones are significantly superior to the earlier ones. In addition, IV generation drugs are also effective against non-spore-forming anaerobes, including strains resistant to the action of early fluoroquinolones. New fluoroquinolones are called “respiratory” for their activity against respiratory pathogens, as well as the ability to penetrate well into the mucous membrane of the respiratory tract and bronchial secretions.

New fluoroquinolones such as levofloxacin, sparfloxacin, moxifloxacin, gatifloxacin, gemifloxacin, sitafloxacin, clinafloxacin, etc. are gradually entering clinical practice.

Levofloxacin (tavanic) - the levorotatory isomer of ofloxacin combines the high effectiveness of ofloxacin with the molecule's resistance to biotransformation in the body and the possibility of developing 2 dosage forms. At the same time, levofloxacin is 2 times more active than ofloxacin against the background of better tolerability. The drug is active against enterococci, Pseudomonas aeruginosa (but inferior to ciprofloxacin), chlamydia, mycoplasmas, Staphylococcus aureus and Staphylococcus epidermidis, the causative agent of gas gangrene.

It is quite natural that, along with ofloxacin, one of the most active fluoroquinolones, ciprofloxacin, has not been ignored by researchers. Intensive searches among its analogs (compounds containing a cyclopropyl radical in position 1) resulted in the creation of fluoroquinolones such as sparfloxacin, grepafloxacin, moxifloxacin, gatifloxacin, gemifloxacin, sitafloxacin, clinafloxacin. Moxifloxacin and gatifloxacin have OCH3 as a substituent at position 8. Sparfloxacin is a difluoroquinolone (6,8 PC) with an amino group at position 5.

Sparfloxacin (Sparflo) is more effective than ciprofloxacin against gram-positive bacteria (including strains resistant to ciprofloxacin), chlamydia, mycoplasmas, mycobacterium tuberculosis and leprosy. The high effectiveness of the drug against mycobacteria is of significant interest in the combination therapy of tuberculosis and leprosy. Sparfloxacin is slowly eliminated from the body (half-life is 16–20 hours), which allows it to be used once a day. The drug is not available in injection form, which somewhat limits its use in the clinic.

Similar in spectrum and degree of activity are such monofluorinated analogues of ciprofloxacin as moxifloxacin, gatifloxacin, gemifloxacin, sitafloxacin, grepafloxacin, clinafloxacin. The listed drugs are traditionally more active against gram-positive aerobic microorganisms, mycoplasmas, mycobacteria (especially moxifloxacin, gatifloxacin and gemifloxacin). Gatifloxacin is considered a promising drug for inclusion in combination therapy for tuberculosis. In terms of activity against gram-negative aerobic microorganisms, they are inferior to ciprofloxacin.

Grepafloxacin (Raxar) is a drug with antipseudomonal activity that approaches the action of ciprofloxacin. Raksar is highly active against gram-positive cocci and mycoplasmas, creates high tissue and intracellular concentrations, and is characterized by long-term elimination from the body.

Moxifloxacin (Avelox), like all 8-methoxy-6-PC derivatives, simultaneously inhibits the functions of two target enzymes for fluoroquinolones (topoisomerase IV and DNA gyrase), and therefore has high bactericidal activity and an increased ability to prevent the selection of resistant mutants. Moxifloxacin is highly active against gram-positive and gram-negative microorganisms (including multidrug-resistant microorganisms), anaerobes and atypical pathogens. The drug is one of the most active fluoroquinolone against staphylococci (including methicillin-resistant) (MIC90 0.015-2 mg/l). It is superior to ciprofloxacin and levofloxacin in its effect on mycoplasmas and ureaplasmas, and in its effect on chlamydia - ciprofloxacin and ofloxacin. The effectiveness of the drug against spore-forming and non-spore-forming anaerobes is comparable to imipenem, metronidazole and clindamycin. Moxifloxacin is superior to the action of ciprofloxacin, ofloxacin and levofloxacin against tubercle bacilli, also showing activity against multidrug-resistant strains of mycobacteria (MIC90 0.5 mg/l). The strength of the antipneumococcal effect is second only to sitafloxacin and gemifloxacin. The drug has only an oral dosage form, but it is also planned to create an injectable form.

It should be noted that research into naphthyridonecarboxylic acid derivatives (analogues of nalidixic acid) has proven to be very promising in the creation of new highly effective drugs. The first drug in this series was temafloxacin, followed by trovafloxacin.

Trovafloxacin (Trovac) - the spectrum of action of the drug is comparable to that of imipenem. Streptococci, methicillin-sensitive staphylococci, anaerobes, enterobacteria, and Haemophilus influenzae are highly sensitive to the drug. The activity of the drug against a number of strains of Pseudomonas aeruginosa exceeds the activity of ciprofloxacin.

Along with the creation of effective drugs among fluorinated derivatives, exploratory studies were also conducted among quinolones not substituted at position 6 with fluorine, which resulted in the production of the compound BMS264756 with activity exceeding moxifloxacin, other analogs of ciprofloxacin and trovafloxacin, and characterized by more optimal pharmacokinetics. This compound exhibits low chondrotoxicity in experiments on immature animals and is currently undergoing clinical trials.

All fluoroquinolones are quickly and well absorbed from the gastrointestinal tract. Food, as a rule, slows down the absorption of drugs, but does not reduce their bioavailability. The absorption of fluoroquinolones is impaired when taking antacids containing aluminum and magnesium, sucralfate, and iron supplements simultaneously. Bioavailability for most fluoroquinolones when taken orally is 80–100% (Table 2), except for norfloxacin (20–40%). The maximum concentration in the blood is reached after 1–2.5 hours. Protein binding is within 20–50% (norfloxacin and moxifloxacin - 10%).

Fluoroquinolones penetrate well into body tissues and fluids, alveolar macrophages, polymorphonuclear leukocytes, bile ducts, respiratory tract, lungs, gastrointestinal mucosa, kidneys, genitals, urine, saliva, sputum, bile, alveolar fluid. The drugs penetrate into the cerebrospinal fluid worse, but with meningitis the penetration rate increases. The highest rates of penetration into the central nervous system are observed with pefloxacin and trovafloxacin. Concentrations of fluoroquinolones in many tissues are close to or higher than serum concentrations. For example, lomefloxacin, due to its optimized pharmacokinetics, creates a concentration in organs and tissues that is 2–7 times higher than the concentration in blood plasma.

All fluoroquinolones are metabolized to form inactive metabolites. The drugs are slowly eliminated from the body. The half-life for most second-generation drugs is 5–9 hours, and for new fluoroquinolones it is 10–20 and even 36 hours (rufloxacin). Such a long elimination period, as well as the presence of post-antibiotic action, allows them to be prescribed 2 times (early fluoroquinolones) or 1 time per day.

Fluoroquinolones are excreted by the kidneys through glomerular filtration and tubular secretion, as well as with bile and feces. In this case, ofloxacin and lomefloxacin are excreted mainly by the kidneys, pefloxacin - with bile, and other drugs - both with the kidneys and with bile.

Fluoroquinolones are highly effective drugs. The scope of application of second-generation drugs is, as a rule, nosocomial infections of various origins and localization: infections of the respiratory tract, abdominal cavity, skin and soft tissues, bones and joints, meningitis, intestinal, urogenital infections, septicemia, bacteremia, some of them are used in complex treatment tuberculosis. Fluoroquinolones of III–IV generations are the drugs of choice in the treatment of community-acquired infections caused by penicillin-resistant strains of S. pneumoniae, S. aureus, H. influenzae, M. catarrhalis. They are used to treat infections of the respiratory tract, bones and soft tissues, and urogenital infections. Drugs such as trovafloxacin and moxifloxacin, which have a very wide spectrum of antimicrobial activity, including also anaerobic microorganisms and methicillin-resistant staphylococci, may in the future be the means of choice in the empirical treatment of the most severe infections in a hospital - severe community-acquired pneumonia, respiratory-associated pneumonia, sepsis, mixed aerobic-anaerobic intra-abdominal and wound infections.

Fluoroquinolones are relatively low-toxic drugs. However, even with their use, adverse events may occur. For some new drugs, undesirable side effects were identified not during experimental studies, but already during widespread use in the clinic. The development of side effects is usually associated with changes in the structure of individual drugs (Table 7).

Table 7

Dependence of the toxic effects of fluoroquinolones on the position of substituents in the quinolone ring of the molecule

Position of the substituent in the ring	Risk of toxic effects				Solubility
Position of the substituent in the ring	Phototoxicity*	Hepatotoxicity	Interaction with theophylline	CNS effects	Solubility
N1	-	+	+	-	-
C5	+	+	-	-	-
C6 (including the position of the main fluorine atom)	-	-	-	-	-
C7	-	++	+	++	++
X8	++	++	-	-	++

Note
* - mainly with the introduction of fluoride

Most often (3–6% of patients) reactions occur from the gastrointestinal tract (nausea, changes in taste, diarrhea, abdominal pain, etc.) and the central nervous system (1–4% of patients) - headache, dizziness, irritability , sleep disturbance; the development of seizures is mainly observed in patients predisposed to them (epilepsy, hypoxia, traumatic brain injury, simultaneous administration with theophylline).

In 0.5–2% of those taking fluoroquinolones, allergic reactions occurred, including the development of anaphylactic shock (with intravenous administration of drugs). When using fluoroquinolones, rare adverse reactions are also possible, such as tendinitis and tendovaginitis, associated with impaired synthesis of peptidoglycan in the tendon structure (drug discontinuation is necessary, tendon ruptures are possible, mainly in elderly people). Most often, this complication is caused by pefloxacin. Rare side effects also include pseudomembranous colitis, candidiasis, transient interstitial nephritis and crystalluria.

Adverse liver events were observed in 2–3% of patients receiving fluoroquinolones. As a rule, the hepatotoxic effect is manifested by an increase in the level of serum transaminases and alkaline phosphatase in the blood serum, which normalizes after discontinuation of the drugs. However, when using fluoroquinolones, cases of more severe damage to the liver and biliary tract may occur, such as hepatitis, liver necrosis, liver failure, cholestatic jaundice. Hepatotoxicity most often occurs with the use of new fluoroquinolones. Trovafloxacin has the greatest hepatotoxic effect (9% of patients). Under the influence of the drug, the level of transaminases in the blood can increase 3 or more times higher than normal. In addition, during the widespread use of trovafloxacin, hepatitis of varying severity, some even fatal, was reported in 140 adult patients with severe infections.

Therefore, in June 1999, the US Food and Drug Administration (FDA) was forced to recommend that trovafloxacin be prescribed only to patients with serious or life-threatening infectious diseases and only in hospital settings. In Europe, trovafloxacin is completely prohibited for use.

When affecting the cardiovascular system, it is necessary to note the ability of fluoroquinolones to prolong the QT interval on the ECG. Changes in the QT interval are recorded experimentally for all fluoroquinolones and are dose-dependent. However, with early fluoroquinolones this effect occurs at very high doses, while newer fluoroquinolones can exhibit this effect at low doses. The occurrence of paroxysmal ventricular tachyarrhythmias and other severe ventricular arrhythmias is characteristic of sparfloxacin, grepafloxacin, gatifloxacin and, to a lesser extent, moxifloxacin and levofloxacin. For example, during the widespread clinical use of grepafloxacin, 7 cases of unexpected deaths were observed, accompanied by cardiac arrhythmias, and therefore in 1999 the drug was withdrawn from the pharmaceutical market by the developer. In clinical practice, QT prolongation during fluoroquinolone therapy is rare and accounts for only 0.01–0.001% of cases. Despite this, fluoroquinolones should be prescribed with caution to patients suffering from severe cardiovascular pathology, as well as when combining these drugs with drugs that can cause prolongation of the QT interval: antiarrhythmics (quinidine, sotalol, amiodarone), antihistamines (terfenadine, astemizole), psychotropic (fluoxetine), macrolides, co-trimoxazole, imidazoles and antimalarial drugs similar to quinolones.

Fluoroquinolones are phototoxic. This effect is most pronounced in the trifluoroquinolone fleroxacin, the difluoroquinolones sparfloxacin and lomefloxacin, as well as in the monofluorinated drug clinafloxacin. The development of the photoelectric effect is associated with the possible destruction of the fluoroquinolone molecule under the influence of UV irradiation, the induction of free radicals and, as a consequence, skin damage. It should be noted that clinafloxacin, which has the greatest phototoxicity (obviously due to the presence of chlorine at position 8 of the quinolone ring), is currently not recommended for use.

The effect of fluoroquinolones on the blood system was discovered with the use of the trifluoroquinolone temafloxacin after the widespread use of the drug was approved. The syndrome caused by temafloxacin, later called “temafloxacin syndrome,” was recorded only with the use of this drug and consisted of the development of severe reactions associated with impaired blood clotting in combination with renal failure and subsequent death. This predetermined the fate of the drug, which was excluded from the nomenclature of drugs in 1993.

It is well known that fluoroquinolones have age restrictions in their use. This is due to the presence of arthrotoxic effects identified in experiments in immature animals (dogs). However, over the past 12 years, fluoroquinolones have been successfully used to treat children for life-saving reasons with severe bacterial infections and the failure of previous antibiotic therapy. At the same time, the drugs were prescribed in a wide age range - from newborns to adolescents. The most frequently prescribed drugs by pediatricians were ciprofloxacin, ofloxacin, pefloxacin, and norfloxacin. As a result of the use of fluoroquinolones, no specific pathological changes were identified in cartilage tissue in children in comparison with control groups. There is an opinion that the possibility of developing arthropathy arises in the presence of a history of articular pathology or as a manifestation of an allergic reaction. Among the new fluoroquinolones, a clinical study of moxifloxacin in an injectable dosage form for children is planned.

Fluoroquinolones can affect the cytochrome P-450 system and the metabolism of methylxanthines (theophylline, caffeine). The most pronounced effect is exerted by enoxacin, which inhibits the clearance of theophylline by 45–75%, less pronounced by ciprofloxacin and pefloxacin (18–32% and 18–31%, respectively). Ofloxacin, lomefloxacin, fleroxacin, sparfloxacin, rufloxacin, temafloxacin, trovafloxacin, moxifloxacin do not affect the metabolism of theophylline.

In conclusion, it should be noted that the class of fluoroquinolones has not exhausted its capabilities and is of great interest for clinical practice and research into the production of new highly effective compounds for the treatment of severe nosocomial and non-hospital infections of various locations.

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Fluoroquinolones of the third generation. Fluoroquinolones antibiotics drug names

Approaches to systematization

Pharmacological features

Application in clinical practice

Undesirable effects and contraindications for use

The use of fluoroquinolones in diseases of the ENT organs

Classification of quinolones

Mechanism of action

Activity spectrum

Pharmacokinetics

Adverse reactions

Common to all quinolones

Characteristic of 1st generation quinolones

Characteristic for fluoroquinolones (rare and very rare)

Indications

First generation quinolones

Fluoroquinolones

Contraindications

For all quinolones

Additionally for 1st generation quinolones

Additionally for all fluoroquinolones

Warnings

Drug interactions

Patient Information

Table. Drugs of the quinolone/fluoroquinolone group. Main characteristics and application features

Classification of quinolones

Mechanism of action

Activity spectrum

Pharmacokinetics

Contraindications

For all quinolones

Additionally for 1st generation quinolones

Additionally for all fluoroquinolones

Warnings

Drug interactions

Patient Information

Table. Drugs of the quinolone/fluoroquinolone group. Main characteristics and application features

Fluoroquinolones

Table. Drugs of the quinolone/fluoroquinolone group.
Main characteristics and application features

Table. Drugs of the quinolone/fluoroquinolone group.
Main characteristics and application features