Meropenem high bactericidal activity against a broad range of aerobic and anaerobic bacteria due to the high capacity meropenem penetrate cell walls of bacteria, a high level of stability to most β-lactamases and significant affinity to various penicillin binding proteins (PRP).
Tests in vitro show that meropenem acts synergistically with various antibiotics. In tests in vitro and in vivo showed that meropenem has a post-antibiotic effect.
Microorganisms can possess one or more of the mechanisms of resistance to meropenem: impaired permeability of the cell wall of gram-synthesizing porins for violations; decrease in affinity for the target PSB; activation of efflux mechanisms; production of beta-lactamases, which are under the influence of hydrolysis of carbapenems.
The only dianabol side effects recommended response criteria to meropenem based on pharmacokinetics and correlation of clinical and microbiological data – zone diameter and MIC determined for the respective pathogens.
The threshold of sensitivity for Streptococcus pneumoniae and Haemophilus influenzae meningitis -. 0.25 mg / l 2. Strains MIC for which higher sensitivity threshold, rare or not detected at the moment. In identifying such a strain on the MIC test is conducted again, the confirmation result of the strain are sent to the reference laboratory, and the strain is considered resistant to receiving confirmation of clinical effect with respect to it. 3. The values used only with meningitis. 4. For all other agents, according to the pharmacokinetic and pharmacodynamic data, without taking into account the specifics of the MIC distributions of specific pathogens. 5. the sensitivity of the test is not recommended, because this pathogen is not the optimal target for meropenem.
Sensitivity to meropenem be determined using standard methods. Interpretation of results must be carried out in accordance with local guidelines.
The efficacy against pathogens listed below, confirmed by the experience of clinical application and guidelines on antibiotic therapy:
Pathogens that are sensitive to meropenem: Grampolozhitelnye aerobes: of Enterococcus faecalis 1 of Staphylococcus aureus (methicillin-sensitive) 2 The genus of Staphylococcus (methicillin-sensitive), including of Staphylococcus epidermidis of Streptococcus agalactiae group B group Streptococcus milleri (S. anginosus, S. constellatus , S. intermedins ) of Streptococcus pneumoniae of Streptococcus pyogenes group A Gramotritsatelnye aerobes: Citrobacter freudii Citrobacter koseri of Enterobacter aerogenes of Enterobacter cloacae of Escherichia coli of Haemophilus influenzae of Klebsiella oxytoca of Klebsiella pneumoniae Morganella morganii of Neisseria meningitidis the Proteus mirabilis the Proteus vulgaris of Serratia marcescens Grampolozhitelnye anaerobes: of Clostridium perfringens Peptoniphilus asaccharolyticus genus Peptostreptococcus (including P. micros , P anaerobius, P. magnus) Gramotriiatelnye anaerobes: of Bacteroides caccae Vacteroides fragilis Prevotella bivia Prevotella disienspathogens for which acquired resistance urgent problem: Grampolozhitelnye aerobes: of Enterococcus faecium 1 Gramotriiatelnye aerobes: The genus of Acinetobacter Burkholderia cepacia of Pseudomonas aeruginosa pathogens that have natural resistance: Gramotritsatelnye aerobes: Stenotrophomonas maltophilia are . of Legionella spp Other pathogens: of Chlamydophila pneumoniae of Chlamydophila psittaciCoxiella burnetii of Mycoplasma pneumoniae
1 Pathogens that have intermediate sensitivity. 2 All methicillin-resistant staphylococci are dianabol side effects resistant to meropenem.
Intravenous for 30 min Meronem drug ® healthy volunteers leads to maximum plasma concentration of about 11 ug / ml for a dose of 250 mg, 23 ug / ml for a dose of 500 mg and 49 ug / ml for a dose of 1 g
, however, in respect of the maximum concentration (C max ) and area under the curve “concentration-time» (AUC) is not absolutely proportional pharmacokinetic The dependence of the administered dose.Marked decrease in plasma clearance from 287 to 205 ml / min for doses from 250 mg to 2 g
intravenous bolus injection preparation Meronem ® in healthy volunteers for 5 minutes results in a maximum plasma concentration of about 52 ug / ml for a dose of 500 mg 112 ug / ml – a dose of 1
through 6 hours after intravenous administration of 500 mg meropenem plasma concentration falls below the 1 mg / ml and below.
Extended (up to 3 hours) infusion carbapenems could lead to optimize their pharmacokinetic and pharmacodynamic parameters. With the standard 30-minute infusion in healthy volunteers, two doses of 500 and 2000 mg every 8 hour time-weighted% T> MIC (ratio between the period of time when the drug concentration exceeds the MIC, and the dosing interval; MIC = 4 ug / ml) was respectively 30% and 58%.When administered to volunteers of the same dose by 3-hour infusions every 8 hours figure% T> MIC increased to 43 and 73%) respectively for 500 and 2000 mg. The mean plasma concentration in healthy volunteers after intravenous bolus over 10 minutes 1000 mg exceeded MIC 4 ug / mL for 42% of the dosing interval compared to 59% at 3-hour infusion of 1000 mg.
Meropenem penetrates well in most tissues and body fluids, including in the cerebrospinal fluid of patients with bacterial meningitis, reaching concentrations in excess to suppress wanted most bacteria.
repeated administration of meropenem at intervals of 8 hours, the patient with normal renal function, accumulation of the drug is observed. In patients with normal renal function, the half-life of about 1 hour.Plasma protein binding is approximately 2%.
About 70% of an intravenous dose of the drug Meronem ® excreted by the kidneys in unchanged form within 12 hours, after which determined a minor renal excretion. Meropenem concentrations in urine above 10 mcg / ml are maintained for 5 hours after dosing with 500 mg. When modes of administration of 500 mg every 8 hours or 1 g every 6 hours was not observed accumulation of meropenem in plasma and in the urine of volunteers with normal liver function.
The only metabolite of meropenem is microbiologically inactive.
Studies in children have shown that the pharmacokinetics of Meronem drug ® in children and similar in adults. The half-life of meropenem in children under 2 years are approximately 1.5-2.3 hours, in the dose range 10-40 mg / kg there is a linear relationship. Renal impairment Pharmacokinetic studies in patients with renal insufficiency have shown that the clearance of meropenem correlates with creatinine clearance. These patients require dose adjustment. Pharmacokinetics study of the elderly showed a decrease in clearance of meropenem which correlated with age-related decrease in creatinine clearance.Meropenem appear in hemodialysis with clearance of approximately 4 times greater than the clearance of meropenem in patients with anuria. Hepatic impairment Pharmacokinetic studies in patients with liver disease have shown that these lesions are not okazvzayut effect on the pharmacokinetics of meropenem.
Meronem ® is indicated for the treatment of children (aged 3 months) and adults following infectious and inflammatory diseases caused by one or more sensitive to meropenem agents:
– pneumonia, including nosocomial pneumonia
– an infection of the urinary system;
– abdominal infection
– infectious-inflammatory diseases of the pelvic organs, such as endometriosis;
– infections of the skin and its structures;
. Empirical therapy of adult patients with suspected infection with symptoms of febrile neutropenia in monotherapy or in combination with anti-viral or anti-fungal drugs
Efficiency Meronem drug ® proved as a monotherapy, or in combination with other antimicrobial agents in the treatment of polymicrobial infections.
Hypersensitivity to meropenem or other drugs carbapenems group in history.
Severe hypersensitivity (anaphylactic reaction, severe skin reaction) to any antibacterial agent having beta-lactam structure (ie to penicillins or cephalosporins).
Children up to 3 months.
Concomitant use of potentially nephrotoxic drugs. Patients with complaints from the gastrointestinal tract (diarrhea), especially suffering from colitis.
Application of pregnancy and during breastfeeding
The safety of in women during pregnancy has not been studied. Animal studies have not shown any adverse effects on the developing fetus.
dianabol side effects should not be used during pregnancy except in cases where the potential benefit to the mother of his application exceeds the potential risk to the fetus. In each case, the drug should be used under strict medical supervision. Breastfeeding Period The data on the allocation of meropenem in breast milk. Should not be used during breastfeeding, except in cases where the potential benefit for the use of the drug by the mother outweighs the potential risk to the child. Evaluate the benefits for the mother should take a decision on the termination of breastfeeding or the abolition.
Dosing and Administration
Dose and duration of therapy should be set depending on the type and severity of the infection and condition of the patient.
The recommended daily dose of 500 mg intravenously every 8 hours with the treatment of pneumonia, urinary tract infections, gynecological infections such as endometritis, infections of skin and skin structure;
1 g IV every 8 hours in the treatment of nosocomial pneumonia, peritonitis, suspected bacterial infection in patients with symptoms of neutropenia and septicemia.
in the treatment of meningitis the recommended dosage is 2 g every 8 hours.
Secure the dose of 2 g as a bolus injection poorly understood .