In Vitro and In Vivo Evaluation of Ceftezole, a New Cephalosporin Derivative

Abstract

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.

Comparison of antibacterial activity of a new cephalosporin, ceftizoxime (FK 749) with other cephalosporin antibiotics.

“…The antibacterial activity of FK 749 against clinical isolates was compared with that of SCF 963, Sodium(6R,7R)-7-[(Z)-2-methoxyiminc-2-(2-aminothiazole-4-yl)acetamidol-8-oxo-5-thia-I-a abicyclo [4,2,0] and were somewhat inferior to SCE 963 and cefmetazole (mean: 1.37 and 1.78 pg/ml, respectively).…”

Pharmacokinetic Interpretation of Blood Levels and Urinary Excretion Data for Cefazolin and Cephalothin After Intravenous and Intramuscular Administration in Humans

“…It was synthesized and studied extensively in Japan (6, 11-13, 16) before being developed for clinical use in the United States. Pharmacokinetic studies in normal subjects have shown higher and more prolonged serum levels with cefazolin than with other cephalosporin antibiotics, e.g., cephaloridine and cephalothin (3,11,16,17). While the drugs were under clinical investigation at Smith Kline & French Laboratories, a series of studies were undertaken to obtain additional human pharmacology data on cefazolin and compare it with cephalothin (2).…”

Safety and Efficacy of Cefazolin Sodium in the Management of Bacterial Infection and in Surgical Prophylaxis

“…1, 3 The serum half-life of cefazolin was reported to be approximately 2 hours for the intramuscular route. 1,17,18 For the intravenous route, it was slightly shorter, approximately 1.5 hours, compared with the intramuscular route (Fig.…”

“…A total of 74%-86% of cefazolin is bound to serum proteins. 3,23 Approximately 90% of cefazolin sodium is excreted in the urine as unchanged drug and is minimally metabolized in the liver. 3,24 Recommended dosage and dosage intervals based on pharmacokinetics and pharmacodynamics (Pk-PD) concepts…”

“…It has also been used for septicemia due to susceptible gram-positive cocci (except Enterococcus) and against some gram-negative bacilli, including E. coli, Proteus, and Klebsiella, which may be susceptible. 2,3 After the introduction of penicillins and other cephalosporins, β-lactamase-producing staphylococci became more prevalent, and occasional outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) were noted. As a result, vancomycin use increased; however, very recently and most alarmingly, vancomycin-resistant strains, such as vancomycin-resistant Enterococcus (VRE) and the vancomycin-resistant MRSA, which had acquired the enterococcal vanA gene, have been described in the US.…”