Penicillin G acylases (PGAs) are industrially important enzymes primarily used for the synthesis of first- and second-generation cephalosporins or penicillins. This study aims to establish a high-efficiency biosynthetic system for cefradine on the purpose of significantly enhancing its catalytic efficiency in cefradine synthesis and developing its potentials for industrial application. In this study, we identified and engineered penicillin G acylase and obtained a highly active mutant KsPGA M7(M168F/F313G) for the synthesis of cefradine. The mutant achieved a conversion rate over 95% in the scaled-up reaction. To validate its industrial applicability, we immobilized both the wild-type and mutant enzymes and applied them in continuous flow reactions, which achieved a space-time yield of 2 800 g/(L·d). This study lays a foundation for the future applications of penicillin G acylases in the industrial synthesis of cefradine.
Penicillin Amidase/biosynthesis* ; Protein Engineering/methods* ; Cephradine/metabolism* ; Escherichia coli/metabolism* ; Enzymes, Immobilized/metabolism* ; Recombinant Proteins/biosynthesis*

Construction of a successful near infrared analysis model is a complex task. It spends a lot of manpower and material resources, and is restricted by sample collection and model optimization. So it is important to study on the extended application of the existing near infrared (NIR) models. In this paper, cephradine capsules universal quantitative model was used as an example to study on the feasibility of its extended application. Slope/bias correction and piecewise direct standardization correction methods were used to make the universal model to fit to predict the intermediates in manufacturing processes of cephradine capsules, such as the content of powder blend or granules. The results showed that the corrected NIR universal quantitative model can be used for process control although the results of the model correction by slope/bias or piecewise direct standardization were not as good as that of model updating. And it also indicated that the model corrected by slope/bias is better than that by piecewise direct standardization. Model correction provided a new application for NIR universal models in process control.
Anti-Bacterial Agents ; chemistry ; Calibration ; standards ; Cephradine ; chemistry ; Feasibility Studies ; Models, Chemical ; Spectroscopy, Near-Infrared ; methods

The effects of cephradinum and ceftazidime on the metabolism of Escherichia coli (E. coli) DH5alpha was determined by microcalorimetry. The microbial activity was recorded as power-time curves through an ampoule method with a TAM Air Isothermal Microcalorimeter at 37 degrees C. The parameters such as the growth rate constant (k), inhibitory ratio (I), the maximum power output (Pm) and the time (tm) corresponding to the maximum power output were calculated. The results show that the ceftazidime has a better inhibitory effect on E. coli DH5alpha than cephradinum.
Anti-Bacterial Agents ; administration & dosage ; pharmacology ; Calorimetry ; methods ; Ceftazidime ; administration & dosage ; pharmacology ; Cephradine ; administration & dosage ; pharmacology ; Escherichia coli ; drug effects ; growth & development ; metabolism ; Microbial Sensitivity Tests

OBJECTIVE: To establish a new high performance liquid chromatography (HPLC) method for determining the concentration of cefazolin, cefradine, cefoperazone and cefotaxime in blood and urine, as well as to investigate its applicability. METHODS: Protein in blood and urine was precipitated directly by acetonitrile with acetanilide was used as the internal standard using Agilent Zorbax SB-Aq column (250 mm x 4.6 mm, 5 microm). The mixed solvents of water (triethylamine 0.12%, acetic acid 0.12%) and acetonitrile were used as the mobile phase to separate cephalosporins using gradient elution method at 1 mL/min (flow rate) and 254 nm (detection wavelength). RESULTS: The working curve of four cephalosporins showed a good correlation (r = 0.9993), with the detection limit up to 0.01 microg/mL. The recovery rate was more than 81.2%. CONCLUSION This method is fast, easy and accurate. It is suitable for biological analysis of the 4 cephalosporins of the blood and urine in practical cases.
Adult ; Anti-Bacterial Agents/urine* ; Cefazolin/urine* ; Cefoperazone/urine* ; Cefotaxime/urine* ; Cephalosporins/urine* ; Cephradine/urine* ; Chromatography, High Pressure Liquid/methods* ; Forensic Toxicology ; Humans ; Male ; Sensitivity and Specificity ; Specimen Handling

Anaphylaxis is an acute life-threatening event, presenting with various clinical symptoms. However, each pathophysiologic mechanism has not been completely understood. We report a case of atypical duodenal ulcers after cephradine induced anaphylactic shock. A 33-year-old woman was injected intravenously of cephradine and propofol for genoplasty, and anaphylactic reaction developed. After the recovery of shock, the patient who complained severe epigastric pain showed unusual endoscopic findings which were are multiple, irregular and shallow ulcerations at the bulb and the second portion of the duodenum. The symptom got improved after ulcer treatment. Histologically, the ulcerating inflammation was detected with eosinophilic infiltration and vascular thrombi. The skin provocation test for cephradine was positive. We suggest that the atypical duodenal ulcer was induced by transient ischemic mucosal injury and chemical damage due to the anaphylactic reaction.
Adult ; Anaphylaxis* ; Cephradine ; Duodenal Ulcer* ; Duodenum ; Eosinophils ; Female ; Humans ; Inflammation ; Propofol ; Shock ; Skin ; Ulcer

Pyogenic vertebral osteomyelitis, which is not uncommon in adults, is rare in children. Furthermore, the clinical presentation is often subtle and nonspecific. As a result, vertebral osteomyelitis is often not considered in the initial evaluation in children, resulting in a delay in diagnosis and treatment. We report a 3-year-old boy who was eventually diagnosed with pyogenic vertebral osteomyelitis and treated successfully with antibiotics. The patient initially presented himself with mild fever and abdominal pain for one week. Urinary tract infection, initially considered due to dysuria with suprapubic tenderness, was ruled out. Further investgation revealed that he had right sided suprapubic tenderness and low abdominal pain. He refused to sit or walk, and preferred a recumbent position with his knees bent. The magnetic resonance imaging study showed findings of L2-L3 vertebral osteomyelitis. With 4 weeks of intravenous cephradine treatment, the patient improved clinically and radiologically.
Abdominal Pain ; Adult ; Anti-Bacterial Agents ; Cephradine ; Child ; Child, Preschool ; Diagnosis ; Discitis ; Dysuria ; Fever ; Humans ; Knee ; Magnetic Resonance Imaging ; Male ; Osteomyelitis* ; Urinary Tract Infections

There were many studies to investigate the pathogenesis and prevention of infection in artificial joint replacement due to the difficulty in management of infected arthroplasty in spite of using large amounts of antibiotics. Biomaterials play a major role in the development of infection because of the way the body responds to their chemical and physical characteristics. Exopolysaccharide glycocalyx or biofilm(slime) which is produced by organisms adhered to the biomaterials has been detected and regarded as an important factor in pathogenesis. The production of slime on the biomaterials in turn makes the pathogens resistant to the antibiotics and therefore they survive. The objects of this study are to evaluate which materials are more susceptible to the adherence by Staphylococcus epidermidis, to evaluate the amount of antibiotics needed to kill the S. epidermidis adhered to the biomaterials(Polymethymethacrylate, Titanium-6Aluminum-4Vanadium alloy, Ultrahigh molecular weight polyethylene), and to evaluate the timing of administration of the antibiotics(cephradine, gentamicin) and potadine for prevention of postoperative infection. The results are as follows. 1. The materials in order of greatest adherence due to the number of organisms colonized are poly- methylmethacrylate(PMMA), ultrahigh molecular weight polyethylene(UHMWPE), and titanium alloy(Ti-6A1-4V alloy) being the least adherent. 2. With the production of biofilm the S. epidermidis becomes resistant to even that of 4 times the minimum bactericidal concentration(MBC) of antibiotics. 3. For prevention of postoperative infection, the prophylactic administration of cephradine if effective when used within 4 hours after contamination and the gentamicin and potadine are effective when used within 8 hours after the contamination with S. epidermidis.
Alloys ; Anti-Bacterial Agents ; Arthroplasty ; Biocompatible Materials ; Biofilms ; Cephradine ; Colon ; Gentamicins ; Glycocalyx ; Joints ; Molecular Weight ; Staphylococcus epidermidis ; Titanium

This is a report of clinical study on the 63 patients of symptomatic urinary tract infection who were hospitalized at the Department of Pediatrics in Kangnam General Hospital during the period between the May of 1989 and the September of 1992. The observation results were as follows: 1) The frequency of urinary tract infection (UTI) was the highest in children under the age of one year (66.7%). 35 patients were male, while the other 28 were female. The ratio of male and female patients was 1.25:1. 2) Fever was observed in most of the cases. Systemic nonspecific manifestation was predominant in the infancy and early childhood, whereas local symptom of UTI was predominant in the late childhood. Among the 35 male patients, 32 cases were phimoses. As for the other 3 cases, Phimoses were not identified. 3) E. coli had the most frequency (65.3%), followed by Klebsiella, Enterobacter, Pseudomonas in descending order. 4) In the vitro antimicrobial susceptibility test, Gram negative organisms such as E. coli Klebsiella, Enterobacter were sensitive to cefotaxime, amikacin, and ampicillin/sulbactam. Meanwhile, Gram positive organisms such as Staphylococcus, Enterococcus were sensitive to vancomycin and cephradine. 5) The renal ultrasonography test was performed for 59 patients, 13 cases of whom showed abnormal findings. 6 cases out of the 13 abnormal patients had hydronephrosis. 6) DMSA renal scan was performed for 40 patients within 2 months of an acute pyelonephritic attack. Signs of pyelonephritic change were found in 18 patients. DMSA scan was repeated 4~12 months later in 4 of these patients. This showed renal cortical scarring in all patients. 7) Voiding cystourethrographic findings in 38 patients showed vesicoureteral reflux in 13 patients. 8) We performed urine culture again after 48 hours from the beginning of therapy and 85.5% of the cases became sterile. 9) The recurrent percentage of UTI was 23.8% with the ratio of 1:1.5 between male and female. Most of the patients were clildren under the age of one year. 10) Operations were made on two cases showing the increase of reflux during the follow-up of unilateral Grade ll and Grade 3 reflux, respectively. Operations were also performed on other two cases with bilateral Grade IV reflux. All the cases were good after the operations. In the meantime, as for another two cases having the right reflux of Grade lland the bilateral reflux of Grade lll, the refluxes were able to be reduced by prophylaxis only, in the course of following up.
Amikacin ; Cefotaxime ; Cephradine ; Child* ; Cicatrix ; Enterobacter ; Enterococcus ; Female ; Fever ; Follow-Up Studies ; Hospitals, General ; Humans ; Hydronephrosis ; Infant* ; Klebsiella ; Male ; Pediatrics ; Phimosis ; Pseudomonas ; Staphylococcus ; Succimer ; Ultrasonography ; Urinary Tract Infections* ; Urinary Tract* ; Vancomycin ; Vesico-Ureteral Reflux

The questions concerning storage temperature and storage duration of the fortified ophthalmic antibiotic solutions are raised. The aim of the current study is to evaluate the influence of fortified ophthalmic antibiotic solutions on its biological and physical properties according to the storage temperature and duration as time goes by. We examined the changes of pH, absorbance spectra, and anti-microbial activity of cefradine(63mg/ml)and gentamicin sulfate(13.6mg/ml) over a four-week period. The results were as follows: There was no difference between the potency of fortified GM solutions stored at 4 degrees C and that at 24 degrees C for 4 weeks. The cefradine stored 24 degrees C exhibited significant changes in both its tJotency and stability after ithe seventh day of storage. The cefradine stored at 4 degrees C exhibited changes in Its absorbance spectra day by day and potency after 14th day.
Cephradine ; Gentamicins ; Hydrogen-Ion Concentration ; Ophthalmic Solutions*

Several of the newer broad-spectrum, potent antibiotics are currently being used for the treatment of meningitis, ventriculitis and shunt-tract infection. The risk of complications following intrathecal administration of some of this newer antibiotics varies considerably. Possible complications of immediate or delayed seizure, cortical electric depression, radiculopathy, transverse myelopathy, and arachnoiditis after intrathecal or intraventricular administration must be weighed against the potential value of this route. These risks may influence the therapeutic management of a specific clinical situation. The author studied the effect of the first generation of cephalosporins(cepalothin, cefazolin, cepharadine, cephapirin), the second generation of cephalosporins(cefamandole, cefmetazole), and the third generation of cephalosporins(cefotaxime, cetriaxone, cefotetan), on electrocortical activity of cerebral cortex. The results are as follows : 1) The topical application of cephalothin, cefazolin, cephapirin 8mg/ml shows electrocortical spike activity. In higher concentration, each cases show intense electrocortical spike activity. The topical application of cephradine 100mg/ml shows electrocortical spike activity and in higher concentration, electrocortical spike activity continued. 2) The topical application of cefamandole 64mg/ml shows electrocortical spike activity first and that of cefmetazole 100mg/ml shows electrocortical spike activity and in higher concentration of each cases, intense electrocortical spike activity continued. 3) The topical application of cefotaxime 16mg/ml shows electrocortical spike activity and that of ceftriaxon 200mg/ml and cefatetan 100mg/ml shows mild electrocortical spike activity. In higher concentration of each cases, electrocortical spike activity continued. In conclusion, the degrees of epileptogenic effect was most severe in the first generation of cephalosporins and the second generation of cephalosporins and the third generation of cephalosporins on the decreasing order.
Anti-Bacterial Agents ; Arachnoid ; Arachnoiditis ; Cefamandole ; Cefazolin ; Cefmetazole ; Cefotaxime ; Ceftriaxone ; Cephalosporins* ; Cephalothin ; Cephapirin ; Cephradine ; Cerebral Cortex* ; Depression ; Meningitis ; Radiculopathy ; Seizures ; Spinal Cord Diseases