無水イミペネム 化学特性,用途語,生産方法
効能
抗生物質, 細胞壁合成阻害薬
説明
Imipenem is a chemically stable thienamycin derivative with an antibacterial
activity that is broader in spectrum and of greater potency than most of the third
generation cephalosporins. Combination with cilastatin, an inhibitor of renal
brush-border dehydropeptidase-I, increases both urinary and plasma levels of
imipenem.
化学的特性
White Crystals
使用
Carbapenem antibacterial.
抗菌性
Imipenem shows potent activity against a wide range of Grampositive
and Gram-negative aerobes and anaerobes, including
many resistant to other agents.Concentrations
(mg/L) inhibiting 50% of strains of other organisms are:
Listeria monocytogenes, 0.03; Legionella pneumophila, 0.03;
Enterococcus faecium, 4; Yersinia spp., 0.06. Mycobacterium fortuitum
is inhibited by 6.25 mg/L. Imipenem is active against
many Pseudomonas species, but not Sten. maltophilia. It is
active against most anaerobes, with the exception of Cl. perfringens,
which is only moderately susceptible. It is bactericidal
at 2–4 times the MIC for most species, but some strains
of Staph. aureus exhibit ‘tolerance’ . Bactericidal
synergy with aminoglycosides, glycopeptides, fosfomycin and
rifampicin (rifampin) has been observed against many strains
of Staph. aureus and enterococci.
Antibacterial activity is unaffected by the presence of cilastatin,
which is itself devoid of antimicrobial activity.
Imipenem is stable to hydrolysis by most serine β-lactamases,
with the exception of the group 2f carbapenem-hydrolyzingenzymes hydrolyzingenzymes
. Strains of B. fragilis, Aeromonas spp.
and Sten. maltophilia can produce metallo-β-lactamases that
hydrolyze the drug rapidly. These strains, in addition to occasional
strains of enterobacteria, Acinetobacter baumannii and
Ps. aeruginosa, show variable resistance to imipenem depending
upon the level of carbapenem-hydrolyzing enzymes and
the presence or absence of imipenem-specific porins. Efflux
pumps also exist that may extrude imipenem from Gramnegative
bacteria.
獲得抵抗性
Some strains of Citrobacter, Enterobacter, Proteus vulgaris,
Providencia, Ps. aeruginosa and Serratia spp. may be resistant
to imipenem and other β-lactam agents, often because
of the selection of stably derepressed mutants expressing
high levels of group 1 β-lactamases coupled with decreased
intracellular drug levels due to porin mutations or increased
efflux.
Induction of class 1 β-lactamases by imipenem in strains
of Aeromonas, Pseudomonas and Serratia spp. is responsible
for antagonism of β-lactamase-labile β-lactam agents in vitro.
Imipenem resistance in Ps. aeruginosa can occur following
selection of mutants that hyperproduce the group 1 cephalosporinase
and which are also deficient in an outer membrane
protein (OprD or D2) which specifically transports
imipenem, but not cephalosporins or monobactams.
一般的な説明
Thienamycin was found in the culture broth of Streptomyces cattleya by Merck Sharp & Dohme in 1976, as a very unstable substance. It has a unique carbapenem structure, like that of the olivanic acids found in S. olivaceus by Beecham Research Laboratories in 1979. Thienamycin shows excellent activity against a variety of pathogenic bacteria, including Pseudomonas aeruginosa. Its chemical stability has been improved by derivatization with the formimidoyl group, and its biological stability has been improved by combining it with cilastatin, an inhibitor of kidney dihydropeptidase. The combination drug imipenem – cilastatin is now under study to evaluate its clinical efficacy and safety.
臨床応用
Lower respiratory tract infections
Urinary tract infections (complicated and uncomplicated)
Intra-abdominal infections
Gynecological infections
Bacterial septicemia
Bone and joint infections
Skin and skin structure infections
Endocarditis
Polymicrobial infections
副作用
CNS effects such as confusional states and seizures have been
reported, especially when recommended doses were exceeded,
and in patients with renal failure or creatinine clearances of
≤20 mL/min/1.73 m2.
Other reactions include phlebitis/thrombophlebitis (3.1%),
nausea (2.0%), diarrhea (1.8%) and vomiting (1.5%).
Increased hepatic enzymes may be seen in adults and children.
Superinfection with Aspergillus, Candida and resistant
Pseudomonas spp. have been described and pseudomembranous
colitis has been reported.
Patients with a history of hypersensitivity reactions to penicillins,
cephalosporins or other β-lactam antibiotics should be
treated cautiously with carbapenems.
無水イミペネム 上流と下流の製品情報
原材料
準備製品