Ceftezole sodium

The pharmacokinetics of ceftezole, a new cephalosporin antibiotic, was studied in 15 patients with normal and impaired renal function after administering the drug in a 2-hour intravenous drip infusion of 2 g. 81% of the infused dose was excreted in the first 6 h urine of the patients with normal renal function. The pharmacokinetic parameters of ceftezole were obtained by analyzing the serum level data of the drug using a one-compartment open model. The mean serum half-life of ceftezole was 0.64 h in patients with normal renal function and was prolonged to 10.7 h in patients with severely impaired renal function (creatinine clearance: 0-2.6 ml/min.). There was a significant linear correlation between the elimination rate of the drug and creatinine clearance.

Aim:To study the crystalline characteristics of ceftezole sodium.Methods:Ceftezole sodium crystals were obtained from different solvents. X-ray diffraction, DSC, TGA, etc were used to analyze the crytals.Results:Ceftezole sodium crystal was easily obtained in isopropanol-water mixture. It consists of ceftizole sodium monohydrate, which consists of type I and type II two different crystal forms. Powder X-ray diffraction patterns showed differences between type I and the type II crystal forms. Peaks at 8 degrees and 18 degrees in diffractograms of the type I, but at 9 degrees and 18.6 degrees in the type II could be observed. Water molecules in different crystal forms had different combining condition. They lost during 35-117 degrees C in the type I form, but lost during 110-160 degrees C in the type II form.Conclusion:Structure of ceftizole sodium monohydrate crystal obtained in different circumstance could be some vary, which influence upon the thermal stability of the compound. The type I crystal form is more stable than the type II.

Ceftezole, a new cephalosporin antibiotic similar to cefazolin, has the following chemical structure: (6R,7R)-8-oxo-7[2-(1H-tetrazol-1-yl)acetamido]-3-[(1,3,4-thiadiazol-2-ylthio)methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-carboxylic acid. Ceftezole was found to be a broad-spectrum antibiotic, active in vitro against many species of gram-positive and gram-negative bacteria except Pseudomonas aeruginosa, Serratia marcescens and Proteus vulgaris. The activity of ceftezole against clinical isolates of Escherichia coli and Klebsiella spp. appeared to be nearly equal to that of cefazolin and higher than those of cephaloridine and cephalothin. Cross-resistance was observed between ampicillin and cephaloridine, but not between ampicillin and ceftezole, in susceptibility tests on clinical isolates of P. mirabilis. The in vitro activity was little affected by the inoculum size, the presence of human serum or the test medium. Ceftezole exhibited apparent bactericidal activity at the concentrations above the minimum inhibitory concentration (MIC) against both S. aureus and E. coli. The development in vitro of resistance by S. aureus 209p and E. coli NIHJ to ceftezole after 16 transfers was similar to or somewhat slower than that to other drugs tested. Ceftezole was relatively stable in nutrient broth and minimally degraded in the serum or tissue homogenates of rats. Ceftezole, in a single subcutaneous administration, exhibited somewhat less efficacy in mice against intraperitoneal infections with Streptococcus pyogenes, S. pneumoniae, E. coli, K. pneumoniae or P. mirabilis than either cephaloridine or cefazolin. However, ceftezole exhibited efficacy similar to that of cephaloridine or cefazolin when administered in three doses. Furthermore, ceftezole was as effective as cefazolin in the treatment of experimental abscesses in mice caused by subcutaneous inoculation with S. aureus.

Introduction:Cephalosporins are widely used in clinical treatment of children, but it is difficult to carry out clinical trials and there is no strong evidence of their safety. Therefore, adverse drug reactions (ADR) of cephalosporins can be a public health problem that deserves attention.Methods:ADR reports collected by the Hubei Adverse Drug Reaction Monitoring Center from 2014 to 2019 were analysed. The safety of Cephalosporins was described by descriptive analysis and three signal mining methods, including the reporting odd ratio (ROR), proportional reporting ratio (PRR), and comprehensive standard method (MHRA).Results:The findings indicated that the age groups of 0-1 and 2-3 years had the highest rates of reporting ADRs. Children aged 0-4 years reported more ADRs, while the proportion of severe ADRs was lower than the average (6.63%). Among the 37 cephalosporins, the severe ADRs of ceftezole, ceftazidime, cefoperazone/sulbactam, cefotaxime, ceftriaxone were reported more and the proportion of severe ADRs was higher. The proportion of severe ADRs of most cephalosporin compound preparations was higher than that of corresponding single components. A total of 99.18% of the cases improved after treatment. There were four deaths whose ADRs were mainly anaphylactic shock, dyspnoea, and anaphylactoid reaction. In signal mining, the three methods produced 206 signals that were the same, and 73 of them were off-label ADRs.Conclusion:ADRs were common but not serious in children aged 0-4 years. And the reported rate of serious ADRs in children aged over 4 years increased with age. ADR reports of ceftezole, ceftazidime, cefoperazone/sulbactam, cefotaxime, ceftriaxone were numerous and serious, and the safety of cephalosporin compound preparations in children was doubtful. Ceftezole may cause off-label ADRs including tremor, face oedema, cyanosis, pallor, rigors, and palpitation. The labeling of ADRs in children in cephalosporin instructions and the record of allergic history need to be improved.

Ceftezole, a new cephalosporin derivative, was compared with cefazolin, cephaloridine, and cephalothin. Data obtained indicate that it is a broad-spectrum antibiotic, with almost identical antimicrobial activity against pathogenic organisms isolated from patients. The therapeutic effect of ceftezole on experimental infections in mice was similar to that of cefazolin and was superior to that of cephalothin. The binding of ceftezole to serum proteins was somewhat less than that of cefazolin. The concentrations of ceftezole in the sera of test animals and human volunteers were determined after intramuscular injection of 20 mg/kg and after a single dose of 500 mg, respectively. The concentration of ceftezole in the serum of volunteers peaked at 24.9 mug/ml 15 min after injection and remained effective (about 2.6 mug/ml) at 4 h. The half-life in serum under the same conditions was 56 min, i.e., about one-half that of cefazolin. The 24-h urinary recovery rate was 87.5%. Most of the administered ceftezole was excreted unchanged mainly through the urinary tract. The biliary excretion rate in SD strain rats after intramuscular injection of 20 mg/kg was about 4.4%. As compared with commercially available cephalosporins, ceftezole was second only to cefazolin in biliary excretion rate. Various tissue levels of ceftezole in animals were higher than cephalothin but, with the exception of renal levels in the early stage after administration, were lower than cefazolin.

The distribution of ceftezole in blood and tissues and its excretion after intramuscular or intravenous administration of single doses of 10 and 20 mg/kg were compared with those of cefazolin, cephaloridine and cephalothin. Blood levels of ceftezole in rats and rabbits were lower than those of cefazolin, and higher than those of cephaloridine and cephalothin. Retention time of ceftezole in the blood was somewhat shorter than that of cefazolin. However, blood levels of ceftezole in dogs were nearly the same as those of cefazolin and cephaloridine. The rate of urinary excretion of ceftezole in 24-hour urine after administration in rats and rabbits was found to be higher than those of the other antibiotics tested. In dogs, however, the rate of urinary excretion of ceftezole was nearly the same as that of cefazolin and higher than those of cephaloridine and cephalothin. The biliary excretion of ceftezole in rats and dogs was much higher than those of cephaloridine and cephalothin, but lower than that of cefazolin. Tissue distribution of ceftezole in rats was compared with that of the other antibiotics by intramuscular and intravenous administration. The initial level of ceftezole in the kidneys was found to be substantially higher than those of the other antibiotics. The initial level of ceftezole in the liver and lungs was also slightly higher than those of the other drugs when administered intramuscularly. Tissue levels of ceftezole were somewhat lower than those of cefazolin in rabbits after intravenous administration. Ceftezole attained a higher maximum level in rat lymph by intramuscular administration than the other antibiotics tested. The maximum concentration of ceftezole present in the exudate in the rat inflammatory pouch was higher than that of cefazolin. In rabbits with cerebrospinal meningitis induced by infection of Streptococcus pyogenes, the level of ceftezole in the cerebrospinal fluid was several times higher than that in normal rabbits. The serum level and urinary excretion of ceftezole was examined in 6 healthy male volunteers after intramuscular administration of a single dose of 500 mg. Ceftezole attained a mean maximum serum level of 22.9 mug/ml 30 minutes after administration and disappeared from the blood in about 6 hours. It was excreted rapidly in the urine. The concentration in 1-hour urine was the highest (mean level: 2,667 mug/ml) and the total excretion rate was 92.6%. No metabolites with antimicrobial activity were observed in the urine. No changes in the pattern of plasma level and urinary excretion and no accumulation in the tissues were observed after repeated intramuscular administration of 20 mg/kg of ceftezole in rabbits, 26 times, for 14 days.

The adult volunteers were given 1 g of ceftezole as a single intramuscular dose to investigate the pharmacokinetic profile of this new cephalosporin. The peak average serum concentration, reached 2 h after injection, was 22.5 micrograms/ml, and the t1/2 beta was 1.5 h; urinary recovery was over 80% within 24 h, the majority of injected ceftezole being excreted within 3 hours.

Using a high throughput-compatible assay to screen for potential alpha-glucosidase inhibitors, we found that the beta-lactam antibiotic ceftezole exhibited potent alpha-glucosidase inhibitory activity. In in vitro alpha-glucosidase assays, ceftezole was shown to be a reversible, non-competitive inhibitor of yeast alpha-glucosidase with a Ki value of 5.78 x 10(-7) M when the enzyme mixture was pretreated with ceftezole. Using an in vivo streptozotocin-induced mouse model, we confirmed that blood glucose levels decreased by 30% 20 min after ceftezole treatment (10 mg/kg/day). Expression levels of glycogen synthase kinase-3, peroxisome proliferator-activated receptor-gamma, and uncoupling protein-3 mRNA were also slightly decreased compared to controls following ceftezole treatment. Taken together, these in vivo and in vitro results suggest that ceftezole may be a clinically useful anti-diabetic compound.

To evaluate clinical effects of amoxicillin and clavulanate potassium in the treatment of children with suppurative tonsillitis, 146 children with suppurative tonsillitis were randomly divided into a ceftezole sodium group and an amoxicillin and clavulanate potassium group. The two groups were given anti-infection treatment using different drugs. Symptomatic treatment was carried out once symptoms such as fever appeared. Five to seven days were taken as one treatment course. Blood routine examination and the detection of C-reactive protein (CRP) were performed three days after treatment. Indexes such as the time to the relief of symptoms, the count of white blood cells, the proportion of neutrophil and CRP levels and the incidence of adverse reactions were compared between groups to evaluate the curative effect. The overall response rate of the amoxicillin and clavulanate potassium group was 94.52%, while that of the ceftezole sodium group was 78.08%; the difference was statistically significant (P<0.05). The improvement of white blood cells and CRP levels of the amoxicillin and clavulanate potassium group was more obvious than that of the ceftezole sodium group (P<0.05). The difference of the time to the improvement of symptoms between the two groups had statistical significance; the amoxicillin and clavulanate potassium group was superior to the ceftezole sodium group (P<0.05). No severe drug-related adverse reactions were observed. Amoxicillin and clavulanate potassium dispersible tablet is effective in treating children with suppurative tonsillitis as it can rapidly relieve the clinical symptoms without increasing incidence of adverse reactions.

Ultrasound-mediated method, which can effectively disperse agglomerates or even eliminate agglomeration, has received more and more attentions in industrial crystallization. However, the ultrasound-mediated de-agglomeration mechanism has not been well understood, and no general conclusions have been drawn. In this study, the crystallization and de-agglomeration process of ceftezole sodium agglomerates under ultrasound irradiation were systematically investigated. Kapur function was selected to investigate the de-agglomeration process under different ultrasonic powers. The results revealed that ultrasound could efficiently inhibit agglomeration. Besides, the de-agglomeration of large sized agglomerate particles was found to be easier to occur in comparison with small sized particles due to its higher specific breakage rate. Finally, the de-agglomeration mechanism under ultrasonic irradiation was proposed on the basis of the calculated cumulative breakage functions.