Cefotetan

Description

Cefotetan is comparatively stable, lasting for approximately 24 hours at room temperature when reconstituted. Slight yellowing and slight darkening produce materials that are still acceptable for therapy. Cefotetan is chemically incompatible with tetracycline, aminoglycosides, and with heparin, often forming precipitates with them. With respect to its molecular mode of action, it has a special affinity for PBP-3 of Gram-negative bacteria, consequently producing filamentous forms. It also binds well with PBP-1A and -1B,therefore leading to cell lysis and death. Whereas it is stable to a wide range of β-lactamases, it also is a potent inducer in some bacteria.

Chemical properties

Off-White Solid

The Uses of Cefotetan

Cefotetan disodium is an antibiotic related to Cephalosporin, used in the treatment of bacterial infections.

Background

A semisynthetic cephamycin antibiotic that is administered intravenously or intramuscularly. The drug is highly resistant to a broad spectrum of beta-lactamases and is active against a wide range of both aerobic and anaerobic gram-positive and gram-negative microorganisms.

What are the applications of Application

Cefotetan is an antibiotic related to Cephalosporin used to treat bacterial infections

Indications

For prophylaxis and treatment of bacterial infections.

Definition

ChEBI: Cefotetan is a semi-synthetic second-generation cephamycin antibiotic with [(1-methyl-1H-tetrazol-5-yl)sulfanyl]methyl, methoxy and {[4-(2-amino-1-carboxy-2-oxoethylidene)-1,3-dithietan-2-yl]carbonyl}amino groups at the 3, 7alpha, and 7beta positions, respectively, of the cephem skeleton. It is resistant to a wide range of beta-lactamases and is active against a broad spectrum of aerobic and anaerobic Gram-positive and Gram-negative microorganisms. It has a role as an antibacterial drug. It is a conjugate acid of a cefotetan(2-).

brand name

Cefotan (Zeneca).

Antimicrobial activity

A semisynthetic cephamycin formulated as the disodium salt for intravenous administration. The activity is similar to that of cefoxitin, but cefotetan exhibits more potent activity against enterobacteria and more modest activity against Staph. aureus.
A 1 g intravenous dose achieves a serum concentration of 140–180 mg/L. There is no evidence of accumulation on a dosage of 1 g every 12 h. Tissue fluid concentrations are about 30% of the simultaneous serum level. The plasma half-life is about 3 h and protein binding is around 88%.
About 85% of the drug is eliminated in the urine over 24 h. Accumulation in renal failure is inversely related to the creatinine clearance, the plasma half-life rising to 20 h in patients requiring hemodialysis. During hemodialysis the half-life falls to around 7.5 h and on peritoneal dialysis it falls to 15.5 h, 5–10% of the dose being recovered in the dialysate over 24 h.
Side effects are those typical of the group. Anaphylaxis has been described. Because of the methylthiotetrazole side chain there is some risk of hypoprothrombinemia, and disulfiramlike reactions can occur. Marked changes in the bowel flora, with appearance of C. difficile, have been reported. Uses are similar to those of other cephamycins, but it is not widely available.

General Description

Cefotetan was synthesized by Yamanouchi Pharmaceutical Co. in 1979 starting with oganomycin, a cephamycin, produced by Streptomyces oganoensis YG19Z. Its 7β side chain, 1,3-dithietan, is unique and contributes greatly to its strong activity against gramnegative bacteria, including Serratia, Citrobacter, Enterobacter, indole-positive Proteus, and anaerobes. Its half-life in the serum is as long as three hours, and about 90 % of it is excreted in the urine.

Pharmacokinetics

Cefotetan is a semisynthetic cephamycin antibiotic that is administered intravenously or intramuscularly. The drug is highly resistant to a broad spectrum of beta-lactamases and is active against a wide range of both aerobic and anaerobic gram-positive and gram-negative microorganisms.

Pharmacokinetics

Cefotetan is a semisynthetic cephamycin antibiotic that is administered intravenously or intramuscularly. The drug is highly resistant to a broad spectrum of beta-lactamases and is active against a wide range of both aerobic and anaerobic gram-positive and gram-negative microorganisms.

Synthesis

Cefotetan, 7|?-[(-carbamoylcarboxylatomethylen)-1,3-dithietan-2-yl]-carboxamido-7-methoxy-3-(1-methyltetrazol-5-yl)-thiomethyl-3-cefem-4-carboxylic acid (32.1.2.43), is synthesized by the following scheme. First, trisodium salt of 4-carboxy-3-hydroxy-5-mercaptoisothiazole (32.1.2.41) undergoes S-alkylation by 7|?-bromoacetamido-7|á-methoxycephalosporanic acid, which is synthesized by a scheme described previously (32.1.2.31) ?ú (32.1.2.37), the only difference being that the acylation in the stage (32.1.2.35) ?ú (32.1.2.36) is accomplished not with 2-(2-thienyl)acetylchloride, but with bromoacetyl bromide. Next, upon reacting the resulting product (32.1.2.42) with 1-methyl-1,2,3,4-tetrazol-5-thiol in the presence of sodium bicarbonate with the expected replacement reaction, in the reaction conditions a ring rearrangement takes place in which the isothiazole ring is opened, and transformed into a derivative of carbamoylcarboxylatomethylen-1,3-dithiethane, namely cefotetan (32.1.2.43).

Metabolism

No active metabolites of cefotetan have been detected; however, small amounts (less than 7%) of cefotetan in plasma and urine may be converted to its tautomer, which has antimicrobial activity similar to the parent drug.

Mode of action

Cefotetan is a semi-synthetic, broad-spectrum, beta-lactamase-resistant, second-generation cephalosporin antibiotic derived from cephalosporium. The bactericidal activity of cefotetan disodium is caused by an inhibition of bacterial cell wall synthesis via inhibition of cross-linking of peptidoglycans. This results in a reduction of cell wall stability and causes cell lysis. Cefotetan disodium is more active against gram-negative organisms and less active against gram-positive organisms compared to first-generation cephalosporins.