Polymorphic karyotypes in related Acremonium strains

Summary A restriction fragment length polymorphism (RFLP) analysis was performed on six related Acremonium strains. With respect to the restriction fragment pattern, all strains of A. chrysogenum were indistinguishable from each other but showed distinctive differences from those of A. strictum, A. flavum and Cephalosporium polyvaleurum. Using pulsed-field gel electrophoresis, we obtained different chromosome patterns from most of the Acremonium strains. Remarkably, the pattern varies in three related A. chrysogenum strains which also differ in their rate of cephalosporin C biosynthesis. The electrophoretic karyotyping was confirmed by the location of rDNA genes on separate chromosomes. Our data indicate that chromosome translocations in industrial strains may be responsible for increased -lactam synthesis.     

国外头孢菌素市场浅析

目的 :评估国外头孢菌素的市场现状及发展趋势。方法 :对国外头孢菌素的销售、产品结构、研发及生产状况进行分析。结果与结论 :近年来 ,国外头孢菌素市场单品种销售额逐年减少 ,头孢菌素在抗生素中的优势地位逐年下降 ,今后的研发方向是广谱、高效、长效和口服制剂等。     

微波诱变头孢菌素C产生顶头孢霉菌的研究

本实验以头孢菌素C高产菌L32为出发菌株,通过微波诱变,得到变株L32-104,初复筛证明其发酵单位提高20%,且遗传性状非常稳定。该菌株在中试以及大生产中均获成功。实验表明微波诱变法操作简便、安全可靠、方法可行。     

Interaction of human organic anion transporters with various cephalosporin antibiotics

Cephalosporin antibiotics are thought to be excreted into the urine via organic anion transporters (OATs). The purpose of this study was to elucidate the interaction of human-OATs with various cephalosporin antibiotics, using proximal tubule cells stably expressing human-OAT1, human-OAT3 and human-OAT4. Human-OAT1 and human-OAT3 are localized to the basolateral side of the proximal tubule, whereas human-OAT4 is localized to the apical side. The cephalosporin antibiotics tested were cephalothin, cefoperazone, cefazolin, ceftriaxone, cephaloridine, cefotaxime, cefadroxil and cefamandole. All of these cephalosporin antibiotics significantly inhibited organic anion uptake mediated by human-OAT1, human-OAT3 and human-OAT4. Kinetic analysis revealed that these inhibitions were competitive. The inhibition constant (K(i)) values of cefoperazone, cefazolin, ceftriaxone and cephaloridine for human-OAT1 were much lower than those for human-OAT3 and human-OAT4, whereas the K(i) values of cephalothin and cefotaxime for human-OAT3 were much lower than those for human-OAT1 and human-OAT4. Human-OAT4 mediated the bidirectional transport of estrone sulfate, an optimal substrate for human-OAT4. These results suggest that human-OAT1, human-OAT3 and human-OAT4 interact with various cephalosporin antibiotics, and that human-OAT1 and human-OAT3 play a distinct role in the basolateral uptake of cephalosporin antibiotics. Since the K(i) value of cephaloridine for human-OAT4-mediated organic uptake was much higher than that for human-OAT1, the results indicate the possibility that human-OAT4 limits the efflux of cephaloridine, leading to the accumulation of cephaloridine and the induction of nephrotoxicity.     

β-内酰胺族抗菌素的研究——Ⅲ.7-脒硫乙酰胺基头孢菌素酸亚砜衍生物的立体定向合成

为寻找更有效的新头孢菌素衍生物,本文报道了具脒硫基侧链的头孢菌素酸(R)和(S)型亚砜的立体定向合成。(S)-型亚砜衍生物II-(S)系将化合物V直接用过酸氧化,再与各种取代硫脲缩合而得。若将7-ACA转化为Schiff碱再行氧化则可立体定向地合成(R)-型亚砜Ⅶ,继而水解,酰化得Ⅸ。最后与各种取代硫脲缩合可得(R)-亚砜衍生物Ⅱ-(R)。所得各中间体及产物的立体化学均经₁H核磁共振予以证实。     

Therapeutic efficacy of meropenem for treatment of experimental penicillin-resistant pneumococcal meningitis

With the widespread emergence of antimicrobial resistance, combination regimens of ceftriaxone and vancomycin (C+V) or ceftriaxone and rifampin (C+R) are recommended for empirical treatment of pneumococcal meningitis. To evaluate the therapeutic efficacy of meropenem (M), we compared various treatment regimens in a rabbit model of meningitis caused by penicillin-resistant Streptococcus pneumoniae (PRSP). Therapeutic efficacy was also evaluated by the final bacterial concentration in the cerebrospinal fluid (CSF) at 24 hr. Each group consisted of six rabbits. C+V cleared the CSF at 10 hr, but regrowth was noted in 3 rabbits at 24 hr. Meropenem monotherapy resulted in sterilization at 10 hr, but regrowth was observed in all 6 rabbits at 24 hr. M+V also resulted in sterilization at 10 hr, but regrowth was observed in 2 rabbits at 24 hr. M+V was superior to the meropenem monotherapy at 24 hr (reduction of 4.8 vs. 1.8 log10 cfu/mL, respectively; p=0.003). The therapeutic efficacy of M+V was comparable to that of C+V (reduction of 4.8 vs. 4.0 log10 cfu/mL, respectively; p=0.054). The meropenem monotherapy may not be a suitable choice for PRSP meningitis, while combination of meropenem and vancomycin could be a possible alternative in the treatment of PRSP meningitis.     

Electrochemical determination of Cephalothin antibiotic by adsorptive stripping voltammetric technique

A sensitive and reliable stripping voltammetric method was developed to determine Cephalothin antibiotic drug. This method is based on the adsorptive accumulation of the drug at a hanging mercury drop electrode and then a negative sweep was initiated, which yield a well defined cathodic peak at −625 mV versus Ag/AgCl reference electrode. To achieve high sensitivity, various experimental and instrumental variables were investigated such as supporting electrolyte, pH, accumulation time and potential, drug concentration, scan rate, convection rate and working electrode area. The monitored adsorptive current was directly proportional to the concentration of Cephalothin and it shows a linear response in the range from 4×10⁻⁷ to 1.2×10⁻⁶ mol l⁻¹ (correlation coefficient=0.9995) and the detection limit (S/N=3) is 3.3×10⁻⁹ mol l⁻¹ at an accumulation time of 3 min. The developed AdSV procedure shows a good reproducibility, the relative standard deviation R.S.D.% (n=10) at a concentration level of 5×10⁻⁷ mol l⁻¹ was 0.94%. Possible interferences by other pharmaceutical drugs and surfactants have been also evaluated. The applicability of this approach was illustrated by the determination of Cephalothin in pharmaceutical preparation and biological fluids such as serum and urine.     

Evidence for the involvement of GABA(A) receptor blockade in convulsions induced by cephalosporins

There is accumulating evidence that most beta-lactam antibiotics (i.e., cephalosporins and penicillins) have some degree of convulsive activity, both in laboratory animals as well as in clinical settings. The proposed mechanism is suppression of inhibitory postsynaptic responses, mainly mediated by gamma-amino butyric acid (GABA)(A)-receptors (GABA(A)-R). However, comprehensive studies on the convulsive activities of various beta-lactam antibiotics in vivo and in vitro have not been performed. We have therefore examined the convulsive activities of seven different cephalosporins using both in vivo and in vitro models: intracerebroventricular (ICV) administration in mouse; [(3)H]muscimol binding assay (BA) in mouse brain synaptosome; and inhibition of recombinant mouse alpha1beta2gamma2s GABA(A)-Rs in Xenopus oocyte (GR). The rank orders of convulsive activities in mouse (cefazolin>cefoselis>cefotiam>cefpirome>cefepime>ceftazidime>cefozopran) correlated with those of inhibitory potencies on [(3)H]muscimol binding and GABA-induced currents of GABA(A)-R in vitro, with correlation coefficients of ICV:GR, ICV:BA and BA:GR of 0.882, 0.821 and 0.832, respectively. In contrast, none of the antibiotics had affinities for N-methyl-D-aspartate (NMDA) receptors nor facilitatory actions on NMDA receptor-mediated current in oocytes. These results clearly demonstrate that the mechanism of cephalosporin-induced convulsions is mediated predominantly through the inhibition of GABA(A)-R function and not through NMDA receptor modulation.     

不同时间青霉素、先锋霉素皮试结果的研究

青霉素、先锋霉素在临床抗感感染广泛应用，一致认为是疗效高，毒性低，价格低廉的抗生素。由于易出现过敏反应，使用前必须做皮内试验，为了合理使用青霉素，先锋霉素，我们于1997年2月－2001年2月，对5847例次青霉素皮试的病人，1823例次行锋霉素皮试的病人结果进行统计学分析研究。结果表明，青霉素皮试在不同时间操作有不同的结果，11：00－13：00阳性主高，先锋霉素无时间关系。