Levofloxacin is Lisomer of racemic drug of ofloxacin. The antibacterial activity of ofloxacin is mainly related to Lisomer.
As an antibacterial preparation of the class of fluoroquinolones, levofloxacin blocks the DNA-gyre (topoisomerase II) and topoisomerase IV, disrupts supercoiling and cross-linking of DNA breaks (deoxyribonucleic acid), suppresses DNA synthesis, causes profound morphological changes in the cytoplasm, cell wall and membranes.
The mechanism of development of resistance
Resistance to levofloxacin can develop, primarily, by two main mechanisms, namely: a decrease in the intracellular concentration of the drug or changes in the targets of the action of the drug.Change in the targets - two bacterial enzymes of DNA-gyrase and topoisomerase IV are the result of mutations in chromosomal genes encoding DNA-gyrase (gyrA and gyrAT) and topoisomerase IV (rarFROM and parE; grlA and grlB the Staphylococcus aureus). The stability of the drug due to a low intracellular concentration develops as a result of a change in the system of porin channels of the outer membrane of the cell, which leads to a decrease in the intake of fluoroquinolone into gram-negative bacteria, or from efflux pumps. Efflux-mediated resistance is described for pneumococci (PmrA), staphylococci (NorA), anaerobic and gram-negative bacteria. Plasmid-mediated resistance to quinolones (determined based on the qnr gene) was found for Klebsiella pneumoniae and E. coli. It is possible to develop cross-resistance between fluoroquinolones. Single mutations may not lead to clinical stability, but multiple mutations cause clinical resistance to all drugs belonging to the class of fluoroquinolones. The altered porins of external membranes and efflux systems can have broad substrate specificity, affecting several classes of antibacterial agents and leading to multiple resistance.
Installed in vitro and confirmed in clinical studies the effectiveness of Gram-positive aerobes - Enterococcus faecalis, Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis (methicillin-sensitive strains), Staphylococcus saprophyticus, Streptococcus pneumoniae (including multidrug-resistant strains - MDRSP), Streptococcus pyogenes, Gram-negative aerobes - Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens and other microorganisms - Chlamydia pneumoniae, Mycoplasma pneumoniae. With respect to the majority (≥90%) of strains of the following microorganisms in vitro the minimum inhibitory concentrations of levofloxacin (2 μg / ml or less) have been established, however, the efficacy and safety of the clinical use of levofloxacin in the treatment of infections caused by these pathogens has not been established in adequate and well-controlled studies: gram- Staphylococcus haemolyticus, Streptococcus (Group C/F), Streptococcus (Group G), Streptococcus agalactiae, Streptococcus milleri, Streptococcus viridans; gram-negative aerobes - Acinetobacter lwoffii, Acinetobacter baumannii, Bordetella pertussis, Citrobacter (diversus) koseri, Citrobacter freundii, Enterobacter aerogenes, Enterobacter sakazakii, Klebsiella oxytoca, Morganella morganii, Pantoea (Enterobacter) agglomerans, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Pseudomonas fluorescens; Gram-positive anaerobes - Clostridium perfringens.
Sensitive microorganisms:
- aerobic gram-positive microorganisms - Corynebacterium diphtheriae, Enterococcus spp., Including Enterococcus faecalis, Listeria monocytogenes, Staphylococcus spp. (coagulase-negative methicillin-sensitive / leukotoxin-containing / moderately sensitive strains),including Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus epidermidis (methicillin-susceptible strains), Streptococcus spp. Groups C and G, Streptococcus agalactiae, Streptococcus pneumoniae (penicillin susceptible / moderately sensitive / resistant strains), Streptococcus pyogenes, Streptococcus spp. groups of viridans (penicillin-sensitive / resistant strains);
- aerobic gram-negative microorganisms - Acinetobacter spp., Including Acinetobacter baumannii, Acinetobacillus actinomycetecomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter spp., Including Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (ampicillin susceptibles / resistant strains), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella spp., including Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis (producing and non-producing beta-lactamase strains), Morganella morganii, Neisseria gonorrhoeae (producing and non-producing penicillinase strains), Neisseria meningitidis , Pasteurella spp., Including Pasteurella canis, Pasteurella dagmatis, Pasteurella multocida, Proteus vulgaris, Providencia s pp., including Providencia rettgeri, Providencia stuartii, Pseudomonas spp., including Pseudomonas aeruginosa, Serratia spp., including Serratia marcescens, Salmonella 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 leprae, Mycobacterium tuberculosis, Mycoplasma hominis, Mycoplasma pneumoniae, Rickettsia spp., Ureaplasma urealyticum.
Moderately sensitive microorganisms (MIC of more than 4 mg / l):
- aerobic gram-positive microorganisms - Corynebacterium urealyticum, Corynebacterium xerosis, Enterococcus faecium, Staphylococcus epidermidis (methicillin-resistant strains), Staphylococcus haemolyticus (methicillin-resistant strains);
- aerobic gram-negative microorganisms - Burkhoideria cepacia, Campylobacter jejuni, Campylobacter coli;
- anaerobic microorganisms - Bacteroides thetaiotaomicronron, Bacteroides vulgatus, Bacteroides ovatus, Prevotella spp., Porphyromonas spp.
Resistant microorganisms (MIC of more than 8 mg / l):
- aerobic gram positive microorganisms - Corynebacterium jeikeium, Staphylococcus aureus (methicillin cutting- Stent strains), other Staphylococcus spp. (coagulase-negative methyl- lyresistant strains);
- aerobic gram-negative microorganisms - Alcaligenes xylosoxidane;
- other microorganisms - Mycobacterium avium.
Minimum inhibitory concentrations of levofloxacin for certain microorganisms
Microorganism | Sensitive, mg / ml | Resistant, mg / ml |
Pseudomonas spp. | ≤1 | >2 |
Staphylococcus spp. | ≤1 | >2 |
Streptococcus | ≤1 | >2 |
Streptococcus pneumoniae | ≤1 | >2 |
Haemophilus influenzae | ≤1 | >1 |
Moraxella catarrhalis | ≤1 | >2 |
Activity of levofloxacin in vitro approximately 2 times higher than for ofloxacin against representatives Enterobacteriaceae, R. Aeruginosa and Gram-positive microorganisms.
In the case of levofloxacin in the treatment of chlamydial diseases of the organs of vision, concomitant therapy is required.
The degree of sensitivity of microorganisms to levofloxacin can have significant geographical differences.
The maximum concentration of levofloxacin achieved with 0.5% eye drops is more than 100 times greater than the minimum inhibitory concentration (MIC) of levofloxacin for sensitive microorganisms.