Pharmacological properties

Pharmacodynamics

Meropenem has bactericidal effect by inhibition of synthesis of walls of bacterial cells at gram-positive and gram-negative bacteria by linking with penitsillinsvyazyvayushchy proteins (pbp).

As well as for others beta laktamnykh antibacterial agents, time at which concentration of a meropenem exceeded MPK (MPK T) indicated high degree of correlation with efficiency. On preclinical models meropeny showed activity at concentration in the blood plasma exceeding MPK for the infecting microorganisms approximately for 40% of a dosing interval. This target value was not established clinically.

Bacterial resistance to meropeny can result from

: 1) decrease in permeability of an external membrane of gram-negative bacteria (in connection with decrease in products of porin); 2) decrease in affinity to target PBP; 3) increase in an expression of components of the effluxny pump and 4) products beta laktamaz which can hydrolyze karbapenema.

by

In the European Union registered cases of the infectious diseases caused by the bacteria resistant to karbapenema.

Cross resistance between meropenemy and the medicines belonging to classes of hinolon, aminoglycosides, macroleads and tetracyclines taking into account target microorganisms is absent. Nevertheless bacteria can show resistance to more than one class of antibacterial medicaments in case the mechanism involved in action includes impermeability of a cell membrane and/or existence of the effluxny pump(s).

MPK Limit values which were defined during clinical trials by the European committee on determination of sensitivity to antimicrobial medicaments (EUCAST) are given by

below.

Microorganism	Sensitive (S), mg/l	Resistant (R), mg/l
Enterobacteriaceae	≤2	8
Pseudomonas	≤2	8
Acinetobacter	≤2	8
Streptococcus, the A, B, C, G group	≤2	2
Streptococcus pneumoniae 1	≤2	2
Other streptococci	2	2
Enterococcus	−	−
Staphylococcus 2	Note 3	Note 3
Haemophilus influenzae 1 and Moraxella catarrhalis	≤2	2
Neisseria meningitidis 2.4	≤0.25	0.25
Gram-positive anaerobe bacterias	≤2	8
Gram-negative anaerobe bacterias	≤2	8
Extreme values which are not connected with species of microorganisms 5	≤2	8

¹ Boundary value of a meropenem for Streptococcus pneumoniae and Haemophilus influenzae in meningitis is 0.25/l mg/l.

² Strains of microorganisms with MPK value, above extreme S/R value, are very rare or now was not reported about them. Analyses concerning identification and antimicrobial sensitivity in relation to any such isolate need to be repeated and if the result is confirmed, isolate goes to referensny laboratory. Till that time while there are data on the clinical answer of the verified isolates with MPK, above the current extreme values of resistance, isolates should be registered as steady.

Sensitivity of stafilokokk to meropeny is predicted by

³ , proceeding from data of sensitivity to Methicillinum.

⁴ Boundary value of a meropenem for Neisseria meningitidis belongs only to meningitis.

Boundary value which is not connected with species of microorganisms is determined by

⁵ generally proceeding from data of pharmacokinetics and a pharmacodynamics, and does not depend on distribution of MPK of separate types. It is intended for use in respect of the types which are not specified in the table and footnotes.

"Carrying out the analysis by determination of sensitivity is not recommended to

by U-2212" as the look is a bad target for treatment use by medicine.

Prevalence of the acquired resistance can geographically change also in time for separate types therefore it is desirable to rely on local information on resistance of microorganisms, especially at treatment of heavy infections. In case of need, when degree of prevalence of resistance of microorganisms at the local level is such that the advantage of medicine use, at least in relation to some types of infections, raises doubts, it is necessary to address for consultation the expert.

to

list Further pathogenic microorganisms on the basis of clinical experience and therapeutic protocols of treatment of diseases.

Usually sensitive types

• Gram-positive aerobes: Enterococcus faecalis ⁶ , Staphylococcus aureus (metitsillinchuvstvitelny) ⁷ , Staphylococcus species (metitsillinchuvstvitelny), including Staphylococcus epidermidis, Streptococcus agalactiae (group B), Streptococcus milleri group (S. anginosus, S. constellatus and S. intermedius), Streptococcus pneumoniae, Streptococcus pyogenes (group A).
• Gram-negative aerobes: Citrobacter freudii, Citrobacter koseri, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Neisseria meningitides, Proteus mirabilis, Proteus vulgaris, Serratia marcescens.
• Gram-positive anaerobe bacterias: Clostridium perfringens, Peptoniphilus asaccharolyticus, Peptostreptococcus species (including P. micros, P. anaerobius, P. magnus).
• Gram-negative anaerobe bacterias: Bacteroides caccae, group Bacteroides fragilis, Prevotella bivia, Prevotella disiens.

Types for which the acquired resistance can be a problem

• Gram-positive aerobes: Enterococcus faecium ^6.8 .
• Gram-negative aerobes: Acinetobacter species, Burkholderia cepacia, Pseudomonas aeruginosa.

By the nature resistant microorganisms

• Gram-negative aerobes: Stenotrophomonas maltophilia, Legionella species.

Other microorganisms: Chlamydophila pneumoniae, Chlamydophila psittaci, Coxiella burnetii, Mycoplasma pneumoniae.

⁶ Vida which showed natural intermediate sensitivity.

⁷ All metitsillinrezistentny rezistentna staphylococcus to meropeny.

⁸ Indicator of resistance of 50% in one or several countries of the European Union.

Pharmacokinetics. At healthy people of T _½ about 1 h makes of blood plasma; average volume to a raspreda