Description
Moflox Pharmacodynamics
Moxifloxacin is a bactericidal broad-spectrum antibacterial agent, 8-methoxyfluoroquinolone.
Bactericidal effect of moxifloxacin is due to the inhibition of bacterial topoisomerases II and IV, which leads to disruption of replication, repair and transcription of DNA biosynthesis of the microbial cell and, consequently, to the death of microbial cells.
Minimum bactericidal concentrations of moxifloxacin are generally comparable to its minimal inhibitory concentrations.
Mechanisms of resistance
Mechanisms leading to the development of resistance to penicillins, cephalosporins, aminoglycosides, macrolides, and tetracyclines do not affect the antibacterial activity of moxifloxacin.
Cross-resistance between these groups of antibacterial agents and moxifloxacin has not been observed. No cases of plasmid resistance have been observed so far either. The overall incidence of resistance is very low (10-7-10-10).
Resistance to moxifloxacin develops slowly through multiple mutations.
Repeated exposure of microorganisms to moxifloxacin in concentrations below the minimum inhibitory concentration (MIC) is accompanied by only a slight increase in the MIC.
There are cases of cross-resistance to quinolones. Nevertheless, some resistant to other quinolones Gram-positive and anaerobic microorganisms retain sensitivity to moxifloxacin.
It was found that the addition of methoxy group in position C8 to the structure of moxifloxacin molecule increases the activity of moxifloxacin and reduces the formation of resistant mutant strains of Gram-positive bacteria.
The addition of the bicycloamino group at the C7 position prevents the development of active efflux, a mechanism of resistance to fluoroquinolones.
Moxifloxacin in vitro is active against a wide range of Gram-negative and Gram-positive microorganisms, anaerobes, acid-fast bacteria and atypical bacteria such as Mycoplasma spp., Chlamydia spp., Legionella spp. as well as bacteria resistant to lactam and macrolide antibiotics.
Effect on human intestinal microflora
In two studies conducted on volunteers, the following changes in the intestinal microflora after oral administration of moxifloxacin were noted.
There was a decrease in concentrations of Escherichia coli, Bacillus spp., Bacteroides vulgatus, Enterococcus spp., Klebsiella spp. as well as anaerobes Bifidobacterium spp., Eubacterium spp., Peptostreptococcus spp. These changes were reversible within two weeks. Clostridium difficile toxin was not detected.
Indications
Infectious and inflammatory diseases caused by microorganisms sensitive to moxifloxacin:
– Uncomplicated infections of the skin and subcutaneous structures;
– community-acquired pneumonia, including community-acquired pneumonia whose causative agents are strains of microorganisms with multiple resistance to antibiotics*;
– complicated infections of the skin and subcutaneous structures (including infected diabetic foot);
– complicated intra-abdominal infections, including polymicrobial infections, including intraperitoneal abscesses;
– uncomplicated inflammatory diseases of the pelvic organs (including salpingitis and endometritis).
For the treatment of infectious? inflammatory diseases moxifloxacin may be used only as an alternative to other antimicrobial agents.
– acute sinusitis;
– exacerbation of chronic bronchitis;
* Streptococcus pneumoniae with multiple antibiotic resistance includes penicillin-resistant strains and strains resistant to two or more antibiotics from groups such as penicillins (at MIC ? 2 µg/ml), second generation cephalosporins (cefuroxime), macrolides, tetracyclines, trimethoprim/sulfamethoxazole.
Current official guidelines on the use of antibacterial agents must be taken into account.
Contraindications
– Hypersensitivity to moxifloxacin, other quinolones and any other component of moxifloxacin;
– under 18 years of age;
– Pregnancy and breastfeeding;
– history of tendon pathology developed as a result of treatment with quinolone antibiotics;
– In preclinical and clinical studies after the administration of moxifloxacin some changes in electrophysiological parameters of the heart were observed, expressed in the prolongation of the QT interval. Due to this fact, the use of moxifloxacin is contraindicated in patients with the following categories: congenital or acquired documented prolongation of the QT interval, electrolyte disorders, especially unregistered hypokalemia; clinically significant bradycardia; clinically significant heart failure with reduced left ventricular ejection fraction; history of rhythm disturbances with clinical symptomatology;
– moxifloxacin should not be used with other drugs that prolong the QT interval;
– Due to the limited amount of clinical data the use of moxifloxacin is contraindicated in patients with liver dysfunction (class C according to the Child-Pugh classification) and patients with transaminases elevated more than five times the upper limit of normal.
How to use and dosages.
- By mouth.
- Recommended dosage regimen of moxifloxacin: 400 mg 1 time per day for infections listed above. The recommended dosage should not be exceeded.
- The tablets should be swallowed whole without chewing, with plenty of water, regardless of meals.
- Duration of treatment
- The duration of treatment is determined by the localization and severity of the infection, as well as the clinical effect.
– uncomplicated infections of the skin and subcutaneous structures: 7 days;
– community-acquired pneumonia: total duration of step therapy (intravenous injection followed by oral administration) is 7-14 days;
– Complicated infections of the skin and subcutaneous structures: total duration of step therapy (intravenous injection followed by oral administration) is 7-21 days;
– complicated intra-abdominal infections: total duration of step therapy (intravenous injection followed by oral administration) is 5-14 days;
– Uncomplicated inflammatory diseases of the pelvic organs: 14 days;
– Acute sinusitis: 7 days;
– Exacerbation of chronic bronchitis: 5-10 days. - Do not exceed the recommended duration of treatment.
- According to clinical studies, the duration of treatment with moxifloxacin in tablets (capsules) can reach 21 days.
- Patients of elderly age.
It is not required to change the dosage regimen in elderly patients. - Children
Efficacy and safety of moxifloxacin use in children and adolescents has not been established. - Impairment of liver function
Due to the limited amount of clinical data the use of moxifloxacin is contraindicated in patients with severe hepatic impairment (class C according to Child-Pugh classification) and patients with transaminases elevated more than five times the upper limit of normal. - Patients with mild to moderate hepatic impairment (Child-Pugh class A and B) do not require a change in dosing regimen.
- Renal failure
In patients with kidney dysfunction (including in severe renal failure with CKD < 30 ml/min/1.73 m2) as well as in patients on continuous hemodialysis and long term outpatient peritoneal dialysis it is not required to change dosage regimen. - Use in patients of different ethnic groups
No change in dosing regimen is required.
