Leflobact
Leflobact is a synthetic broad-spectrum antimicrobial bactericidal drug from the group of fluoroquinolones, containing levofloxacin, a levorotatory isomer of ofloxacin, as an active substance. Compared to ofloxacin, levofloxacin has a wider spectrum of antibacterial activity, additionally including various streptococci, incl. pneumococci.
Levofloxacin blocks bacterial DNA gyrase (topoisomerase II) and topoisomerase IV, disrupts supercoiling and cross-linking of DNA breaks, inhibits DNA synthesis, causes profound morphological changes in the cytoplasm, cell wall and membrane of microorganisms, but does not affect the enzymes of human cells.
Levofloxacin is active against most strains of microorganisms both in vitro and in vivo.
In
vitro :
Sensitive
to levofloxacin (minimum inhibitory concentration (MIC) <2 mg/ml):
Gram-positive aerobic microorganisms: Corynebacterium diphtheriae, Enterococcus faecalis, Enterococcus spp. (except Enterococcus faecium), Listeria monocytogenes, Staphylococcus spp., coagulase-negative (strains sensitive and moderately sensitive to methicillin), Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis (methicillin-sensitive strains), Streptococcus spp. groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae (sensitive, moderately sensitive and resistant to penicillin), Streptococcus pyogenes, Streptococcus group Viridans (sensitive and resistant to penicillin).
Gram-negative aerobic microorganisms: Acinetobacter baumannii, Acinetobacter calcoaceticus, Acinetobacter spp., Actinobacillus actinomycetemcomitans, Bordetella pertussis, Citrobacter diversus, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Enterobacter spp., Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi , Haemophilus influenzae (strains sensitive and resistant to ampicillin), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella pneumoniae, Klebsiella oxytoca, Klebsiella spp., Moraxella catarrhalis (beta-lactamase producing and non-producing strains), Morganella morganii, Neisseria gonorrhoeae, Neisseria meningiti dis Pasteurella conis, Pasteurella dagmatis, Pasteurella multocida, Pasteurella spp., Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Providencia spp., Pseudomonas aeruginosa, Pseudomonas spp., Salmonella spp., Serratia r marcescens, Serratia spp.
Anaerobic microorganisms: Bacteroides fragilis, Bifidobacterium spp., Clostridium perfringens, Fusobacterium spp., Peptostreptococcus spp., Propionibacterium spp., Veilonella spp.
Other microorganisms: Bartonella spp., Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Legionella pneumophila, Legionella spp., Mycobacterium spp., Mycobacterium leprae, Mycobacterium tuberculosis, Mycoplasma pneumoniae, Mycoplasma hominis, Rickettsia spp., Ureaplasma urealyticum.
Moderately sensitive to levofloxacin (MIC>4 mg/l):
Gram-positive aerobic microorganisms: Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis (methicillin-resistant strains), Staphylococcus haemolyticus (methicillin-resistant strains).
Gram-negative aerobic microorganisms: Burkholderia cepacia, Campylobacter jejuni/coli.
Anaerobic microorganisms: Bacteroides thetaiotaomicron, Bacteroides vulgatus, Bacteroides ovatus, Prevotella spp., Porphyromonas spp.
Resistant to levofloxacin (MIC >8 mg/ml):
Gram-positive aerobic microorganisms: Corynebacterium jeikeium: Staphylococcus aureus (methicillin-resistant strains), Staphylococcus spp. coagulase-negative (methicillin-resistant strains).
Gram-negative aerobic microorganisms: Alcaligenes xylosoxidans.
Other microorganisms: Mycobacterium avium.
LEFLOBACT 5MG/ML FL 100ML SR D/INFUSION
Hospital-acquired infections caused by Pseudomonas aeruginosa (Pseudomonas aeruginosa),
may require combination treatment.
The prevalence of acquired resistance in cultured strains of microorganisms may vary by geographic region and over time. In this regard, information on drug resistance in a specific country is required; for the treatment of severe infections or if treatment is ineffective, a microbiological diagnosis must be established with the isolation of the pathogen and determination of its sensitivity to levofloxacin.
Methicillin-resistant Staphylococcus aureus
There is a high likelihood that methicillin-resistant Staphylococcus aureus will be resistant to fluoroquinolones, including levofloxacin. Therefore, levofloxacin is not recommended for the treatment of known or suspected infections caused by methicillin-resistant Staphylococcus aureus if laboratory tests have not confirmed the sensitivity of this microorganism to levofloxacin.
Disability and potential irreversible serious adverse reactions associated with fluoroquinolones
The use of fluoroquinolones, including levofloxacin, has been associated with disability and the development of irreversible serious adverse reactions from various body systems that can develop simultaneously in the same patient. Adverse reactions caused by fluoroquinolones include tendonitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and nervous system side effects (hallucinations, anxiety, depression, insomnia, headaches, and confusion). These reactions may develop from several hours to several weeks after starting levofloxacin therapy. The development of these adverse reactions was observed in patients of any age or without the presence of previous risk factors. If the first signs or symptoms of any serious adverse reactions occur, use of levofloxacin should be discontinued immediately. Fluoroquinolones, including levofloxacin, should be avoided in patients who have experienced any of these serious adverse reactions.
Duration of infusions
You should strictly adhere to the recommended duration of drug administration, which should be at least 60 minutes (for 100 ml of infusion solution) or 30 minutes (for 50 ml of solution). Experience with levofloxacin shows that increased heart rate and a transient decrease in blood pressure may occur during infusion. In rare cases, vascular collapse may develop. If a significant decrease in blood pressure is observed during the infusion, the drug should be stopped immediately.
Patients predisposed to developing seizures
Like other quinolones, levofloxacin should be used with great caution in patients with a predisposition to seizures. Such patients include patients with previous lesions of the central nervous system, such as stroke, severe traumatic brain injury; patients simultaneously taking drugs that lower the seizure threshold of the brain, such as fenbufen and other similar non-steroidal anti-inflammatory drugs, or other drugs that lower the seizure threshold, such as theophylline (see section “Interaction with other drugs”). If seizures develop, treatment with levofloxacin should be discontinued.
Pseudomembranous colitis
Diarrhea that develops during or after treatment with levofloxacin, especially severe, persistent and/or bloody, may be a symptom of pseudomembranous colitis caused by Clostridium difficile.
If pseudomembranous colitis is suspected, treatment with levofloxacin should be stopped immediately and specific antibiotic therapy (vancomycin, teicoplanin or oral metronidazole) should be started immediately. Drugs that inhibit intestinal motility are contraindicated.
Tendinitis and tendon rupture
Tendinitis has been reported rarely with quinolones, including levofloxacin, and can sometimes lead to rupture of tendons, including the Achilles tendon, and may be bilateral. This side effect may occur within 48 hours of starting treatment or several months after completion of fluoroquinolone therapy. Elderly patients are more prone to developing tendonitis; In patients taking fluoroquinolones, the risk of tendon rupture may be increased with concomitant use of corticosteroids. In addition, post-transplant patients have an increased risk of developing tendonitis, so it is recommended to be careful when prescribing fluoroquinolones to this category of patients. In patients with impaired renal function, the daily dose should be adjusted based on creatinine clearance. Patients should be advised to remain calm at the first sign of tendonitis or tendon rupture and to contact their healthcare provider. If tendonitis or tendon rupture is suspected, treatment with Leflobact should be stopped immediately and appropriate treatment of the affected tendon should be initiated, for example by providing adequate immobilization (see sections “Contraindications” and “Side effects”).
Hypersensitivity reactions
Levofloxacin may cause serious, potentially fatal hypersensitivity reactions (angioedema, anaphylactic shock) (see section "Side effects"). If they develop, you should immediately stop administering the drug and immediately consult a doctor.
Severe bullous reactions
When using levofloxacin, cases of severe bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis have been observed (see section "Side effects"). In case of development of any reactions from the skin or mucous membranes, the patient should immediately inform the doctor, who should decide on further use of the drug in the patient
Disorders of the liver and biliary tract
Cases of hepatic necrosis, including fatal liver failure, have been reported with the use of levofloxacin, mainly in patients with severe underlying diseases, such as sepsis (see section "Side effects"). Patients should be warned to stop treatment and seek immediate medical attention if signs and symptoms of liver damage occur, such as anorexia, jaundice, dark urine, itching and abdominal pain.
Patients with impaired renal function
Since levofloxacin is excreted mainly through the kidneys, patients with impaired renal function require mandatory monitoring of renal function, as well as adjustment of the dosage regimen (see section "Dosage and Administration"). When treating elderly patients, it should be taken into account that patients in this group often have impaired renal function (see section “Dosage and Administration”).
Preventing the development of photosensitivity reactions
Although photosensitivity develops very rarely with the use of levofloxacin, to prevent its development, patients are not recommended to be unnecessarily exposed to strong solar or artificial ultraviolet irradiation (for example, visiting a solarium) during treatment and for 48 hours after the end of treatment with levofloxacin.
Superinfection
As with the use of other antibiotics, the use of levofloxacin, especially for a long time, can lead to increased proliferation of microorganisms that are insensitive to it (bacteria and fungi), which can cause changes in the microflora that is normally present in humans. As a result, superinfection may develop. Therefore, during treatment, it is imperative to re-evaluate the patient’s condition, and, if superinfection develops during treatment, appropriate measures should be taken.
QT
interval prolongation Very rare cases of QT prolongation have been reported in patients receiving fluoroquinolone therapy, including levofloxacin.
When using fluoroquinolones, including levofloxacin, caution should be exercised in patients with known risk factors for prolongation of the QT interval: in elderly patients; in patients with uncorrected electrolyte disturbances (with hypokalemia, hypomagnesemia); with congenital long QT syndrome; with heart disease (heart failure, myocardial infarction, bradycardia); with simultaneous use of drugs that can prolong the QT interval, such as class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, antipsychotics.
Elderly and female patients may be more sensitive to drugs that prolong the QT interval. Therefore, fluoroquinolones, including levofloxacin, should be used with caution (see sections “With caution”, “Dosage and administration”, “Side effects”, “Overdose” and “Interaction with other drugs”).
Patients with glucose-6-phosphate dehydrogenase deficiency
Patients with latent or manifest glucose-6-phosphate dehydrogenase deficiency are predisposed to developing hemolytic reactions when treated with quinolones, which should be taken into account when treating with levofloxacin.
Hypo- and hyperglycemia (dysglycemia)
As with the use of other quinolones, cases of hyperglycemia and hypoglycemia have been observed with the use of levofloxacin. During therapy with levofloxacin, dysglycemia occurred more often in elderly patients and patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (for example, glibenclamide drugs) or insulin. When using levofloxacin in such patients, the risk of developing hypoglycemia, including hypoglycemic coma, increases. It is necessary to inform patients about the symptoms of hypoglycemia (confusion, dizziness, ravenous appetite, headache, nervousness, palpitations or increased heart rate, pale skin, perspiration, trembling, weakness). If the patient develops hypoglycemia, treatment with levofloxacin should be stopped immediately and appropriate therapy should be initiated. In these cases, it is recommended to switch to therapy with an antibiotic other than a fluoroquinolone, if possible. When treating with levofloxacin in elderly patients and patients with diabetes mellitus, careful monitoring of blood glucose concentrations is recommended.
Peripheral neuropathy
Sensory and sensorimotor peripheral neuropathy, which may have a rapid onset, has been reported in patients receiving fluoroquinolone therapy, including levofloxacin. If the patient develops symptoms of neuropathy, levofloxacin should be discontinued. This minimizes the possible risk of developing irreversible changes.
Patients should be informed to report any symptoms of neuropathy to their healthcare provider. Fluoroquinolones should not be prescribed to patients with a history of peripheral neuropathy.
Exacerbation of pseudoparalytic myasthenia gravis (myasthenia gravis)
Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may increase muscle weakness in patients with myasthenia gravis. Post-marketing adverse reactions, including pulmonary failure requiring mechanical ventilation and death, have been associated with the use of fluoroquinolones in patients with myasthenia gravis. The use of levofloxacin in a patient with an established diagnosis of pseudoparalytic myasthenia gravis is not recommended (see section “Side Effects”).
Prevention and treatment of anthrax through airborne transmission
The use of levofloxacin in humans for this indication is based on data on the sensitivity of Bacillus anthracis to it,
obtained from
in vitro
studies and experimental studies conducted in animals, as well as limited data from the use of levofloxacin in humans. Treating physicians should refer to national and/or international documents that reflect the collectively developed point of view on the treatment of anthrax.
Psychotic reactions
Psychotic reactions, including suicidal ideation/attempts, have been reported in patients taking fluoroquinolones, including levofloxacin, sometimes after a single dose. In case of development of any side effects from the central nervous system, including mental disorders, treatment with levofloxacin should be stopped immediately and appropriate therapy should be prescribed. In these cases, it is recommended to switch to therapy with an antibiotic other than a fluoroquinolone, if possible. The drug should be prescribed with caution to patients with psychosis or patients with a history of mental illness.
Visual impairment
If any visual impairment develops, immediate consultation with an ophthalmologist is necessary (see section “Side Effects”).
Effect on laboratory tests
In patients receiving levofloxacin therapy, the determination of opiates in urine may lead to false-positive results, which should be confirmed by more specific methods.
Levofloxacin may inhibit the growth of Mycobacterium tuberculosis
and subsequently lead to false negative results of the bacteriological diagnosis of tuberculosis.
Precautions when handling the drug
To prevent bacterial contamination, the infusion solution should be used immediately (within 3 hours) after piercing the rubber stopper of the bottle. Protection of the solution from light during infusion is not required.
Impact on the ability to drive vehicles and machinery
Side effects of Leflobakt®, such as dizziness or vertigo, drowsiness and visual disturbances (see section “Side effects”), can reduce psychomotor reactions and the ability to concentrate. This may pose a risk in situations where these abilities are of particular importance (for example, when driving a car, when servicing machinery, when performing work in an unstable position).
