Imcitin Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: IMCITIN (imipenem and cilastatin sodium) is a broad spectrum beta­-lactam antibiotic. IMCITIN consists of two components: Imipenem, beta-lactam antibiotic, is a potent inhibitor of bacterial cell wall synthesis by binding to one or more of the penicillin binding protein (PBPs); which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Cilastatin is a specific enzyme inhibitor of dehydropeptidase (DHPI) that blocks the metabolism of imipenem in the kidney, and substantially increases the concentration of intact imipenem in the urinary tract. The antibacterial spectrum of Imipenem is broad including a number of significant pathogens in vitro. Organisms against which lmipenem is usually active include: Aerobic Gram-positive Microorganisms: Staphylococcus aureus (including penicillinase-and nonpenicillinase-producing strains); Staphylococcus epidermidis; Staphylococcus saprophyticus; Streptococcus pneumoniae; Streptococcus pyogenes; Streptococcus agalactiae; Viridans group streptococci; Streptococcus Group C; Streptococcus Group G; Streptococcus Group H; Enterococcus faecalis; Listeria monocytogenes; Bacillus spp.; Nocardia asteroids; Erysipelothrix rhusiopathiae.
But Enterococcus faecium and methicillin-resistant staphylococci are not susceptible to imipenem.
Aerobic Gram-negative Microorganisms: Neisseria gonorrhoeae (including penicillinase-and nonpenicillinase-producing strains); Neisseria meningitides; Haemophilus ducreyi; Haemophilus influenzae (including beta-lactamase and non-beta-lactamase producing strains); Haemophilus parainfluenzae; Enterobacter spp.; Enterobacter agglomerans; Enterobacter cloacae; Enterobacter aerogenes; Escherichia coli; Hafnia alvei; Klebsiella spp.; Klebsiella oxytoca; Klebsiella pneumoniae; Morganella morganii (formerly Proteus morganii); Proteus spp.; Proteus mirabilis; Proteus vulgaris; Providencia spp.; Providencia rettgeri (formerly Proteus rettgetrit); Providencia stuartii; Serratia spp.; Serratia proteamaculans (formerly Serratia liquefaciens); Serratia marcescens; Salmonella spp.; Salmonella typhi; Shigella spp.; Yersinia spp. (formerly Pasteurella); Yersinia enterocolitica; Yersinia pseudotuberculosis; Pseudomonas spp.**; Pseudomonas aeruginosa; Pseudomonas fluorescens; Pseudomonas putida; Acinetobacter spp.; Moraxella catarrhallis (formerly Branhamella catarrhalis); Bordetella bronchiseptica; Eikenella corrodens; Pasteurella multocida; Brucella melitensis; Alcaligenes denitrificans; Alcaligenes xylosoxidans; Aeromonas hydrophila; Plesiomonas shigelloides; Brevundimonas diminuta (formerly Ps. diminuta); Capnocytophaga spp.; Campylobacter spp.; Helicobacter pylori (C.pylori); Legionella pneumophila; Gardnerella vaginalis (formerly Haemophilus vaginalis).
** Stenotrophomonas mallophilia (formerly Pseudomonas meltophilia) and some strains of Burkholderia cepacia (formerly Pseudomonas cepacia) are generally not susceptible to imipenem.
Anaerobic Microorganisms: Actinomyces spp.; Bifidobacterium spp.; Clostridium spp.; Clostridium perfringens; Eubacterium spp.; Lactobacillus spp.; Peptococcus spp.; Peptostreptococcus spp.; Propionbacterium spp.; Bacteroides spp.; Bacteroides fragilis; Bacteroides distasonis; Bacteroides ovatus; Bacteroides thetaiotaomicron; Bacteroides vulgatus; Fusobacterium spp.; Prevotella spp.; Prevotella bivia; Prevotella disiens; Prevotella melaninogenica; Prevotella oralis; Veillonella spp.
Other organism: Mycobacterium fortuitum; Mycobacterium fallax.
Pharmacokinetics: Distribution: Rapidly and widely to most tissues and fluids including sputum, pleural fluid, peritoneal fluid, interstitial fluid, bile, reproductive organs and bone; highest concentrations in pleural fluid, interstitial fluid, peritoneal fluid and reproductive organ; low concentration in CSF; crosses placenta; enters breast milk.
Metabolism/Excretion: Imipenem is metabolized in the kidney by dehydropeptidase 1; activity is blocked by cilastatin; cilastatin is partially metabolized renally. Half-life elimination is 60 minutes; prolonged with renal impairment. Both drugs are excreted in urine (-70% as unchanged drug).