클라불란산 C화학적 특성, 용도, 생산
개요
Clavulanic acid is a mold product with only weak intrinsic antibacterial activity, but it is an excellent
irreversible inhibitor of most β-lactamases. It is believed to acylate the active site serine by mimicking the
normal substrate. Hydrolysis occurs with some β-lactamases, but in many cases, subsequent reactions occur
that inhibit the enzyme irreversibly. This leads to its classification as a mechanism-based inhibitor (or
so-called suicide substrate). The precise chemistry is not well understood, but when clavulanic
acid is added to ampicillin and amoxicillin preparations, the potency against β-lactamase–producing strains
is markedly enhanced.
용도
beta-lactamase inhibitor
정의
ChEBI: Antibiotic isolated from Streptomyces clavuligerus. It acts as a suicide inhibitor of bacterial beta-lactamase enzymes.
World Health Organization (WHO)
The amoxicillin/clavulanic acid combination should be reserved
for infections likely or known to be caused by amoxicillin- resistant beta-lactamase
producing strains. Amoxicillin/clavulanic acid is listed in the WHO Model List of
Essential Drugs.
Antimicrobial activity
It exhibits broad-spectrum but low intrinsic activity, most
MICs being in the range 16–128 mg/L. Enterobacteriaceae
and Staph. aureus are among the more sensitive and Ps. aeruginosa
the most resistant organisms. MICs of 8 mg/L against
H. influenzae and 0.1–4 mg/L for penicillinase-producing
N. gonorrhoeae are notable.
일반 설명
Clavulanic acid was found in the culture broth of Streptomyces clavuligerus by Beecham Research Laboratories in 1976. It was the first β-lactamase inhibitor. This antibiotic shows weak antibacterial activity against grampositive and gram-negative organisms but strong inhibitory activity against the β-lactamase produced by ampicillin-resistant bacteria. Clavulanic acid is used orally in combination with amoxicillin and with ticarcillin by injection to enhance the activities of these antibiotics against resistant infections.
Pharmacokinetics
It exhibits broad-spectrum but low intrinsic activity, most
MICs being in the range 16–128 mg/L. Enterobacteriaceae
and Staph. aureus are among the more sensitive and Ps. aeruginosa
the most resistant organisms. MICs of 8 mg/L against
H. influenzae and 0.1–4 mg/L for penicillinase-producing
N. gonorrhoeae are notable.
Clinical Use
Clavulanic acid is an antibiotic isolated from Streptomycesclavuligeris. Structurally, it is a 1-oxopenam lacking the6-acylamino side chain of penicillins but possessing a 2-hydroxyethylidene moiety at C-2. Clavulanic acid exhibitsvery weak antibacterial activity, comparable with that of6-APA and, therefore, is not useful as an antibiotic. Itis, however, a potent inhibitor of S. aureus β-lactamaseand plasmid-mediated β-lactamases elaborated by Gramnegativebacilli.
Combinations of amoxicillin and the potassium saltof clavulanic acid are available (Augmentin) in variousfixed-dose oral dosage forms intended for the treatment ofskin, respiratory, ear, and urinary tract infections causedby -lactamase–producing bacterial strains. These combinationsare effective against β-lactamase–producingstrains of S. aureus, E. coli, K. pneumoniae, Enterobacter,H. influenzae, Moraxella catarrhalis, and Haemophilusducreyi, which are resistant to amoxicillin alone. The oral bioavailability of amoxicillin and potassium clavulanate issimilar. Clavulanic acid is acid-stable. It cannot undergo penicillanicacid formation because it lacks an amide side chain.Potassium clavulanate and the extended-spectrum penicillinticarcillin have been combined in a fixed-dose, injectableform for the control of serious infections caused byβ-lactamase–producing bacterial strains. This combinationhas been recommended for septicemia, lower respiratory tractinfections, and urinary tract infections caused by β-lactamase–producing Klebsiella spp., E. coli, P. aeruginosa,and other Pseudomonas spp., Citrobacter spp., Enterobacterspp., S. marcescens, and S. aureus. It also is used in bone andjoint infections caused by these organisms. The combinationcontains 3 g of ticarcillin disodium and 100 mg of potassiumclavulanate in a sterile powder for injection (Timentin).
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