Synthesis of cefatrizine by recombinant alpha-amino acid ester hydrolase / 生物工程学报

To explore the enzymatic route of cefatrizine synthesis, alpha-amino acid ester hydrolase (AEH) gene was cloned from the whole genome of Xanthomonas rubrillineans, and expressed heterologously in Escherichia coli BL21 (DE3). The effects of temperature, pH and substrates' molar ratio upon the transformation yield of cefatrizine by purified recombinant AEH were investigated. The monomer of AEH was determined as 70 kDa by SDS-PAGE. The optimal pH and temperature reaction were (6.0 +/- 0.1) and 36 degrees C for cefatrizine synthesis. The transformation yield was 64.3% under 36 degrees C, pH (6.0 +/- 0.1), when the concentrations of two substrates were about 30 mmol/L (7-ATTC) and 120 mmol/L (HPGM x HCl), respectively, and the enzyme consumption was 22 U/mL. The results pave the way for optimization of the industrial enzymatic synthesis of cefatrizine.

In vitro activity of cefadroxil, cephalexin, cefatrizine and cefpirome in presence of essential and trace elements

Evidences supporting the introduction of metallic elements in several biological processes are rapidly accumulating. Likewise, many drugs possess modified toxicological and pharmacological properties when in the form of metal complexes. In order to ascertain the role of various essential and trace element complexation on the antibacterial activity of various cephalosporins, the synergistic or antagonistic behavior of cefadroxil, cephalexin, cefatrizine and cefpirome in presence of essential and trace elements has been studied and compared with the parent drug. The essential and trace elements comprised of magnesium, calcium, chromium, manganese, ferric, cobalt, nickel, copper, zinc and cadmium in the form of their chloride. These studies were carried out by observing the minimum inhibitory concentration [MIC] using agar dilution method and compared with the MIC'S of the standard cephalosporins against various species of Gram [+] and Gram [-] microorganisms such as Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus faecalis, Escherichia coli, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella typhi and Shigella dysenteriae. Different dilutions of cephalosporins and salts of essential and trace elements were used in these studies. The ratio of the drug and metal salts was 1:1 and the reactions were carried out at two different temperatures as 37°C and 60°C in order to study the complex formation. The aim of our study was on one hand to evaluate the changes in microbiological activity of the standard cephalosporins after in vitro metal interactions to study the synergetic or antagonistic behavior of the later through the difference in MICs values of these cephalosporins and on the other hand to access the bioassay directed extent of drug metal complexations. Our investigation reveal that interaction of above cephalosporins with essential and trace elements cause antagonistic effect in many cases which was shown by decrease in antimicrobial activity of cephalosporins and MIC values were increased

In Vitro Activities of Cefatrizine-Clavulanic Acid against Gram-Negative Bacilli Isolated from Community-acquired Urinary Track Infection / 대한진단검사의학회지

BACKGROUND: A high proportion of currently isolated gram-negative bacilli are resistant to beta-lactams by producing beta-lactamases. beta-lactam and beta-lactamase inhibitor combinations have been successfully used to overcome the resistance. In this study, in vitro antimicrobial activity of a new combination, cefatrizine-clavulanic acid, was determined against gram-negative bacilli isolated from community-acquired urinary track infections. METHODS: Nonduplicate strains of Enterobacteriaceae, isolated in 2003 from urine specimens of outpatients and inpatients of less than 3 hospital days at Severance Hospital, were tested by the NCCLS agar dilution method. RESULTS: Of a total of 204 isolates, 144 (71%) were Escherichia coli and 30 (15%) were Klebsiella spp. MIC50 and MIC90 of cefatrizine for E. coli were 2 microgram/mL and 16 microgram/mL, respectively. MIC90s of both cefaclor and cefoxitin were also 16 g/mL. MIC50 and MIC90 of cefatrizine-clavulanic acid for E. coli were 1 microgram/mL and 4 microgram/mL, respectively, which were 1/2-1/4 of those of cefaclor and cefoxitin. For Klebsiella spp., MIC90 of cefatrizine was 4 microgram/mL with an MIC range of 1->128 microgram/mL, whereas that of cefatrizine-clavulanic acid was 2 microgram/mL with an MIC range of 0.5-32 microgram/mL. In vitro activity of cefatrizine-clavulanic acid was higher than that of cefatrizine. CONCLUSIONS: Improved in vitro activity of cefatrizine-clavulanic acid against isolates of E. coli and Klebsiella spp. from community-acquired urinary track infection suggested that the combination is useful for an empirical treatment of the infection.

In Vitro Activities of Cefatrizine/clavulanic Acid Against Major Clinical Isolates of Bacteria / 대한임상미생물학회지

BACKGROUND: beta-lactam antibiotics are one of the most frequently used antimicrobial agents. However, with the increase of beta-lactamase-producing bacteria, penicillins arid 1 st generation cephalosporins have become less useful. Cefatrizine and clavulanic acid combination (CTCA) was developed to restore the activity. The aim of this study was to determine the activities of CTCA against major recent clinical isolates. METHODS: Aerobic and anaerobic bacteria tested were isolated from clinical specimens in Severance Hospital during 1996 to 1999. Antimicrobial susceptibility was determined by the NCCLS agar dilution methods. RESULTS: MICs of cefatrizine (CT) and CTCA were similar for methicillin-susceptible Staphylococcus aureus, Streptococcus pyogenes and S. pneumoniae. For Moraxella (Branhamella) catarrhalis, MIC90 CTCA was 1 microgram/mL, which was 1/8-fold lower than that of cefatrizine. MIC90S of CTCA for Escherichia coli and Klebsiella pneumoniae were 4 microgram/mL and 8 microgram/mL, respectively, which were 1/4- to 1/16-fold lower than those of CT. However, it was less active against Citrobacter freundii, Enterobacter cloacae and Serratia marcescens. Against Bacteroides fragilis group organisms, it showed good activities similar to those of other beta-lactam and beta-lactamase inhibitor combinations. CONCLUSIONS: CTCA showed good antimicrobial activities against M. (B.) catarrhalis, Haemophilus influenzae, Neisseria gonorrhoeae, extended spectrum beta-lactamase-producing E. coli and K. pneumoniae, Proteus vulgaris and B. fragilis. In conclusion, it would be useful for the treatment of infections due to those organisms, and for the empirical treatment of respiratory and urinary tract infections.