Mifloksan Mechanism of Action

Pharmacology: Moxifloxacin is a fourth-generation fluoroquinolone antibacterial agent active against a broad spectrum of Gram-positive and Gram-negative ocular pathogens, atypical microorganisms and anaerobes.
Microbiology: Moxifloxacin has activity against a wide range of Gram-positive and Gram-negative microorganisms. Moxifloxacin inhibits the topoisomerase II (DNA gyrase) and topoisomerase IV required for bacterial DNA replication, transcription, repair, and recombination.
The C8-methoxy moiety of moxifloxacin also lessens the selection of resistant mutants of Gram-positive bacteria compared to C8-H moiety found in older fluoroquinolones. Moxifloxacin's bulky C-7 substituent group interferes with the quinolone efflux pump mechanism of bacteria.
Moxifloxacin is often bactericidal at concentrations equal to or slightly greater than inhibitory concentrations. Fluoroquinolones, including moxifloxacin, differ in chemical structure and mode of action from β-lactam antibiotics, macrolides and aminoglycosides. Therefore organisms resistant to these drugs may be susceptible to moxifloxacin. Resistance to moxifloxacin develops slowly via multiple-step mutations and occurs at a general frequency between 10^-9 to 10^-11 for Gram-positive bacteria.
Moxifloxacin has been shown to be active against most strains of the following microorganisms.
Aerobic Gram-positive Microorganisms: Corynebacterium species; Micrococcus luteus including erythromycin, gentamicin, tetracycline, and/or trimethoprim resistant strains); Staphylococcus aureus (including methicillin, erythromycin, gentamicin, ofloxacin, tetracycline, and/or trimethoprim resistant strains); Staphylococcus epidermidis including methicillin, erythromycin, gentamicin, ofloxacin, tetracycline, and/or trimethoprim resistant strains); Staphylococcus haemolyticus (including methicillin, erythromycin, gentamicin, ofloxacin, tetracycline, and/or trimethoprim resistant strains); Staphylococcus hominis (including methicillin, erythromycin, gentamicin, ofloxacin, tetracycline, and/or trimethoprim resistant strains); Staphylococcus warneri (including erythromycin resistant strains); Staphylococcus pneumoniae (including penicillin, erythromycin, gentamicin, tetracycline and/or trimethoprim resistant strains); Streptococcus viridans group (including penicillin, erythromycin, tetracycline, and/or trimethoprim resistant strains).
Aerobic Gram-negative Microorganisms: Acinetobacter lwoffii; Haemophilus influenzae (including ampicillin resistant strains); Haemophilus parainfluenzae.
Other Microorganism: Chlamydia trachomatis.
The following organisms are considered susceptible when evaluated using systemic breakpoints. However, a correlation between the systemic breakpoint and the ophthalmological efficacy has not been established. The list of the organisms is provided as guidence only in assessing the potential treatment of conjungtival infections. Moxifloxacin exhibits minimal inhibitory concentrations (MICs) of 2 μg/mL or less (systemic susceptible breakpoint) against most (≥90%) strains of the following ocular pathogens.
Aerobic Gram-positive Microorganisms: Listeria monocytogenes; Streptococcus saprophyticus; Streptococcus agalactiae; Streptococcus mitis; Streptococcus pyogenes; Streptococcus group C, G and F.
Aerobic Gram-negative Microorganisms: Acinetobacter baumannii; Acinetobacter calcoaceticus; Citrobacter freundii; Citrobacter koseri; Enterobacter aerogenes; Enterobacter cloacae; Escherichia coli; Klebsiella oxytoca; Klebsiella pneumoniae; Moraxella catarrhalis; Morganella morganii; Neisseria gonorrhoeae; Proteus mirabilis; Proteus vulgaris; Pseudomonas stutzeri.
Anaerobic Microorganisms: Clostridium perfringens; Fusobacterium species; Prevotella species; Propionibacterium acnes.
Other Microorganisms: Chlamydia pneumoniae; Legionella pneumophila; Mycobacterium avium; Mycobacterium marinum; Mycoplasma pneumoniae.
Special Populations: The pharmacokinetic parameters of oral moxifloxacin are not significantly altered by mild, moderate or severe renal impairment. No dosage adjustment of MIFLOKSAN ophthalmic solution is necessary in patients with renal impairment.
Pharmacokinetic parameters of oral moxifloxacin were not significantly altered in patients with mild to moderate hepatic insufficiency (child-pugh classes A and B).
Studies are not performed in patients with severe hepatic impairment (child-pugh classes C). Because of the low systemic exposure by the topical route of administration, no dosage adjustment of MIFLOKSAN ophthalmic solution is needed in patients with hepatic impairment.