We retrospectively evaluated the efficacy and safety of the combination drug piperacillin/tazobactam (PIPC/TAZ) in comparison with those of fourth-generation cephalosporins (4th Cephs) as initial empirical treatment i...We retrospectively evaluated the efficacy and safety of the combination drug piperacillin/tazobactam (PIPC/TAZ) in comparison with those of fourth-generation cephalosporins (4th Cephs) as initial empirical treatment in hematological malignancies patients with febrile neutropenia (FN). Among 200 patients assessed in this study, 49 had received PIPC/TAZ and 151 4th Cephs. Patient background characteristics were comparable between the two treatment groups. The overall efficacy rate in those receiving 4th Cephs and PIPC/TAZ was 57.0% (86/151 patients) and 59.2% (29/49 patients), respectively, with no significant difference detected between the two treatment regimens (P = 0.78). Treat-ment did not need to be discontinued or interrupted due to development of adverse drug reactions in any of the patients. Therefore in this study the efficacy and safety of PIPC/TAZ as initial antimicrobial treatment for FN in patients with hematological malignancies were not inferior to those of 4th Cephs. Based on the preliminary data obtained in this study, we propose to conduct a multicenter, prospective, controlled study to compare PIPC/TAZ versus CFPM given as empirical antimicrobial treatment against FN in patients with hematological malignancies.展开更多
The accelerated weight gain in productive animals as a result of feeding antibiotic enriched fodder has been well known for decades. The better energy harvest is the result of modified gut microbiota as a consequence ...The accelerated weight gain in productive animals as a result of feeding antibiotic enriched fodder has been well known for decades. The better energy harvest is the result of modified gut microbiota as a consequence of applied antibiotics. Similar mechanisms might result obesity in humans as well. Objectives: Finding associations between global antibiotic consumption of different classes in EU countries and obesity data in adults and children prove that antibiotics might play a significant role in the development of obesity “epidemics” and related illnesses. Methods: Antibiotic consumption data were compared with obesity figures in adults and children in European countries and statistically analyzed for significance. Results: Significant correlation was found between the average yearly consumption of cephalosporins (p = 0.007), quinolones (p = 0.031), macrolides (p = 0.000083) and childhood obesity data, but no significant association was observed with the average penicillin consumption. No association was observed between adult obesity and any of the antibiotic classes studied. Conclusions: Our results support the hypothesis that different types of antibiotics might influence the development of obesity among children, and this finding can serve as a unified explanation for the development of obesity “epidemics”, similarly to the obesity and gut flora alteration-related diseases (type 2 diabetes mellitus, autism, etc.).展开更多
In the present study we had an aim to develop the methods of functionalizing the surface of magnetite nanoparticles with cefotaxime and ceftriaxone antibiotics. The quantitative analysis of the nanostructured cephalos...In the present study we had an aim to develop the methods of functionalizing the surface of magnetite nanoparticles with cefotaxime and ceftriaxone antibiotics. The quantitative analysis of the nanostructured cephalosporins was determined by Atom Absorbance Spectroscopy (AAS) and based on the Lambert-Beer law. The engineered nanostructures were tested on gram-negative microorganisms Klebsiella spp., of Enterobacteriaceae, and gram-positive bacteria Staphylococcus aureus, each having multi-drug resistance properties.展开更多
A simple, precise and accurate kinetic spectro-photometric method for determination of ce-fradine anhydrous, cefaclor monohydrate, ce-fadroxil monohydrate, cefalexin anhydrous and cefixime in bulk and in pharmaceutica...A simple, precise and accurate kinetic spectro-photometric method for determination of ce-fradine anhydrous, cefaclor monohydrate, ce-fadroxil monohydrate, cefalexin anhydrous and cefixime in bulk and in pharmaceutical formula-tions has been developed. The method based on a kinetic investigation of the reaction of the free carboxylic acid group of the drug with a mixture of potassium iodate and potassium iodide at room temperature to form yellow coloured triiodide ions. The reaction was followed up spectrophotometrically by measuring the increase in absorbance at 352 nm as a function of time. The initial rate, fixed time, variable time and rate-constant methods were adopted for constructing the calibration curves but fixed time method has been found to be more applicable. The analytical performance of the method, in terms of accuracy and precision, was statistically validated;the results were satisfactory. The method has been successfully applied to the determination of the studied drugs in commercial pharmaceutical formulations. Statistical comparison of the results with a well established reported method showed excellent ag- reement and proved that there is no significant difference in the accuracy and precision.展开更多
A simple, accurate and precise spectrophotometric method has been proposed for the determination of eleven cephalosporins, namely;cefaclor monohydrate, cefadroxil monohydrate, cefalexin anhydrous, cefradine anhydrous,...A simple, accurate and precise spectrophotometric method has been proposed for the determination of eleven cephalosporins, namely;cefaclor monohydrate, cefadroxil monohydrate, cefalexin anhydrous, cefradine anhydrous, cefotaxime sodium, cefoperazone sodium, ceftriaxone sodium, ceftazidime penthydrate, cefazolin sodium, cefixime and cefpodoxime pro- xetil in bulk drug and in pharmaceutical formulations. The method depends on hydrolysis of the studied drugs using 0.5M NaOH at 100°C and subsequent reaction of the formed sulfide ions with NBD-Cl (4-chloro-7-nitrobenzo-2-oxa-1, 3-diazole) to form a yellow-colored chromogen measured at 390 nm. Different variables affecting the reaction (e.g. NaOH concentration, hydrolysis time, NBD-Cl concentration and diluting solvent) were studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients (0.9990- 0.9999) were found in the range of 5-160 μg mL-1 for all studied drugs. The limits of assay detection and quantitiation ranged from 0.289 to 5.867 and from 0.878 to 17.778 μg mL-1;respectively. The accuracy and precision of the proposed method were satisfactory. The method was successfully applied for analysis of the studied drugs in their pharmaceutical formulations and the recovery percentages ranged from 96.6 to 103.5%.展开更多
Theoretical insights elucidate a series of active phosphonate esters application in preparation of Cephalosporin antibiotics’ intermediate. The B3LYP/6-311+G(d,p) method was employed to obtain the stable equilibrium ...Theoretical insights elucidate a series of active phosphonate esters application in preparation of Cephalosporin antibiotics’ intermediate. The B3LYP/6-311+G(d,p) method was employed to obtain the stable equilibrium geometries including comparing to the AE-active ester. It was found that the Ethyl-aminothiazoly Loximate (AT) molecule fragment is almost planar sheet, but it is almost perpendicular to the plane of phosphoryl ester. Moreover, the calculated Mulliken atomic charge distribution and frontier molecular orbital analysis of these esters showed that the amino N atom connected to the Thiazole ring of the AT had the maximum negative charge, which suggested that this area had high molecular activity. The value of ΔEL-H was energy gap between EHOMO and ELUMO and indicated that compound 6a had high reaction activity. The theory calculation results can explain the reaction mechanism well and predict that the novel active phosphonate ester has a hopeful application prospect in preparation of Cephalosporin antibiotics’ intermediate.展开更多
Five new cephalosporin compounds were designed and synthesized, and the antibacterial activities were evaluated by the standard serial 2-fold agar dilution method in vitro. The results showed that the activities of th...Five new cephalosporin compounds were designed and synthesized, and the antibacterial activities were evaluated by the standard serial 2-fold agar dilution method in vitro. The results showed that the activities of the compounds Ia and lb against ESBL E. coli and K. pneumoniae are comparable to those of Cefepime.展开更多
Two universal spectral ranges(4550-4100 cm^(-1) and 6190-5510 cm^(-1))for construction of quantitative models of homologous analogs of cephalosporins were proposed by evaluating theperformance of five spectral ranges ...Two universal spectral ranges(4550-4100 cm^(-1) and 6190-5510 cm^(-1))for construction of quantitative models of homologous analogs of cephalosporins were proposed by evaluating theperformance of five spectral ranges and their combinations,using three data sets of cephalos-porins for injection,ie.,cefuroxime sodium,cetriaxone sodium and cefoperazone sodium.Subsequently,the proposed ranges were validated by using eight calibration sets of otherhomologous analogs of cephalosporins for injection,namely cefmenoxime hydrochloride,ceftezole sodium,cefmetazole,cefoxitin sodium,cefotaxime sodium,cefradine,cephazolin sodium and ceftizoxime sodium.All the constructed quantitative models for the eight kinds of cephalosporinsusing these universal ranges could fulill the requirements for quick quantification.After that,competitive adaptive reweighted sampling(CARS)algorithm and infrared(IR)-near infrared(NIR)two-dimensional(2D)correlation spectral analysis were used to determine the scientific basis of these two spectral ranges as the universal regions for the construction of quantitativemodels of cephalosporins.The CAR.S algorithm demonstrated that the ranges of 4550-4100 cm^(-1) and 6190-5510 cm^(-1) included some key wavenumbers which could be attributed to content changes of cephalosporins.The IR-NIR 2D spectral analysis showed that certain wavenumbersin these two regions have strong correlations to the structures of those cephalosporins that wereeasy to degrade.展开更多
Nine new derivatives of 7 β - (5- methyl- 1- aryl- 1H-1, 2, 3- triazoly- 4- carboxamido) cephalosporins were synthesized by acylction of 7 β -amino group of 7-ACA, 7-ADCA and 7-ACT with 5 -methsyl- 1 -aryl- 1 H- 1,2...Nine new derivatives of 7 β - (5- methyl- 1- aryl- 1H-1, 2, 3- triazoly- 4- carboxamido) cephalosporins were synthesized by acylction of 7 β -amino group of 7-ACA, 7-ADCA and 7-ACT with 5 -methsyl- 1 -aryl- 1 H- 1,2,3-triazoly-4-formyl chloride. The structure of the compounds were confirmed by elementray analysis IR, HNMR and FAB-MS. Some of them showed significant antibacterial activity展开更多
Introduction: Gonorrhoeae and antimicrobial resistance AMR of gonococci is a major health problem today, because emerged resistance to last line empirical treatment for gonorrhoeae cephalosporins in many countries is ...Introduction: Gonorrhoeae and antimicrobial resistance AMR of gonococci is a major health problem today, because emerged resistance to last line empirical treatment for gonorrhoeae cephalosporins in many countries is predictable to be untreatable disease in near future. WHO GASP, WHO GLASS and WHO’s global action plan on AMR recommends to expand nationally and internationally to collect data to monitor AMR of gonococci for public health policies. Objective: Our aim is to detect resistance of gonococci to Cepha- losporins and determine the most effective empirical treatment for un-com- plicated gonococcal urethritis in males in Egypt. Methods: We depended in our methodology on selected gonococci from male urethral discharge specimens on Thyer Martien medium;collected 33 isolates during three years from 2017 to 2020;used antibiotics with MIC according to international standards and measuring IZD according to antimicrobial susceptibility testing reference ranges in international standards. Results: By statistical studies, resistance to cephalosporins was as follows: Cephradine 97%, Cefaclor 87.9%, Cefoxitin 97%, Ceftriaxone 90.9% and 42.4% to Cefepime, that shows hetero-genecity in resistance inside cephalosporin group;while resistance to Macrolides group represented by Azithromycin and Tetracyclins group represented by Doxycycline was as follows: Azithromycin 39.4%, Doxycycilne 27.3%;finally fluoroquinolones, the most effective group, resistance, was as: Levofloxacin 15.2%, Ciprofloxacin 15.2% and Ofloxacin 24.2%. Conclusion: The most effective empirical treatment for uncomplicated gonococcal urethritis in males in EGYPT is Fluoroquinolone;especially Levofloxacin ranks first susceptibility as 78.8% and 15.2% resistance followed by Ciprofloxacin susceptibility as 69.7% and 15.2% resistance, finally Ofloxacin susceptibility as 66.7% and 24.2% resistance;for Ceftriaxone not more recommended in EGYPT as empirical treatment for uncomplicated gonococcal urethritis, it is susceptibility as 6.1% and 90.9% resistance;in addition, we can use combination therapy of Fluoroquinolones with Azithromycin or Doxycycline, whose susceptibility is 30.3% for Azithromycin and 42.4% for Doxycycycline, while resistance is 39.4% for Azithromycin and 27.3% for Doxycycline. It is worth noting that only Cefepime in Cephalosporins group represents 42.4% susceptibility and 42.4% resistance;in addition to the Carbapenems group, it represents as 42.4% susceptibility for Imipenem and 45.5% resistance, then 42.2% susceptibility for Meropenem and 48.5% resistance, which can play role in combination therapy.展开更多
An approach of using molinspiration calculations and molecular docking on PBPs (penicillin-binding proteins) and certain β-lactamases is employed to predict the molecular properties, bioactivity and resistance of n...An approach of using molinspiration calculations and molecular docking on PBPs (penicillin-binding proteins) and certain β-lactamases is employed to predict the molecular properties, bioactivity and resistance of newer and reference cephalosporins. The previously synthesized cephalosporins 1-8 and reference cephalosporins were subjected to extensive evaluations by calculating the molecular properties, drug-likeness scores on the bases of Lipinski's rule and bioactivity prediction using the method of molinspiration web-based software. The TPSA (topological polar surface area), OH-NH interactions, n-violation and the molinspiration Log partition coefficient (miLogP) values were also calculated. The investigated cephalosporins were subjected to molecular docking study on PBPs (lpyy) and on β-lactamases produced by S. aureus, K. pneumonia, E. coil and P. auroginosa using 1-click-docking website. Molecular properties of 1-8 recorded higher "FPSA than cephalexin and were lower than the reference cephalosporins and do not fulfill the requirements for Lipinski's rule. Bioactivities of 1-8 were predicted to be less and their docking scores on PBPs were comparable to those of the reference cephalosporins, particularly ceftobiprole. The references recorded various docking scores on the above β-lactamases and as expected, cefiobiprole recorded the lowest scores on all β-lactarnases. Cephalosporins 1-8 recorded various docking scores on β-lactamases. Molecular docking studies on PBPs and β-lactamases are considered as very useful, reliable and practical approach for predicting the bioactivity scores and to afford some information about the stability and selectivity of the newly proposed cephalosporins against β-lactamases of certain pathogenic microbes, such as P. auroginosa and MRSA, by recording the relative docking scores in comparison with those of reference cephalosporins.展开更多
Objective:An increasing level of antimicrobial resistance to extended-spectrum cephalosporins has been reported,so we conducted this study to investigate the molecular characteristics of cephalosporin resistant Neisse...Objective:An increasing level of antimicrobial resistance to extended-spectrum cephalosporins has been reported,so we conducted this study to investigate the molecular characteristics of cephalosporin resistant Neisseria gonorrhoeae(NG)strains isolated from China Gonococcal Antimicrobial Resistance Surveillance Programme(China-GRSP).Methods:In total,2,038 NG isolates were collected from the China-GRSP between 2015 and 2016.NG multiantigen sequence typing(NG-MAST),multilocus sequence typing(MLST),and NG sequence typing for antimicrobial resistance(NG-STAR)were used to determine characteristics and resistant determinants of cephalosporin-resistant isolates.The results are described as percentages.Results:Seventy-four(3.6%)cephalosporin-resistant isolates were confirmed.MLST_(ST7363)was the most prevalent MLST among cefixime-resistant(CFX-R)isolates,whereas MLST_(ST7365)(n=8)in was the most prevalent sequence type among ceftriaxone-resistant(CRO-R)isolates.CFX-R strains were mainly associated with penA-X(n=27,44.3%),penA-XIII(n=6,9.8%),penA-XVIII(n=5,8.2%),and CRO-R strains were mainly related to penA-XVIII(n=10,25.6%),penA-43(n=9,23.1%),penA-XIII(n=7,17.9%).Conclusion:The main conclusion of this study is that the predominant cephalosporin-resistant clones in China include locally emerged and imported linages.The CFX-R and CRO-R strains are primarily related to penA mutations,and their predominant genotypes are different.With the increase in international travel,tracking high-risk-resistant clones and identifying outbreaks and their associations with epidemiological characteristics are critical to improve public health.展开更多
[Objectives]To establish a HPLC-MS method for the determination of polymer impurities in cefathiamidine and its preparations.[Methods]Kromasil 100-5 C_(18) column(4.6 mm ×250 mm,5μm)was used for analysis;mobile ...[Objectives]To establish a HPLC-MS method for the determination of polymer impurities in cefathiamidine and its preparations.[Methods]Kromasil 100-5 C_(18) column(4.6 mm ×250 mm,5μm)was used for analysis;mobile phase ammonium acetate solution(pH 6.30)-acetonitrile,gradient elution;volumetric flow rate 1.0 mL/min;column temperature 40℃;multi-reaction monitoring mode was used for analysis,and positive ion scanning was chosen as the electrospray ion source.[Results]The resolution between impurities and main peaks under this method was greater than 1.5,and 8 known impurities and 2 polymer impurities could be completely separated and distinguish-ed.It was inferred that the molecular ion peak[M+H]^(+):m/z727.1874,m/z 785.1937 was the possible polymer impurity of this product.[Conclusions]A method for the analysis of polymer impurities in cefathiamidine and its preparations was formed,which could achieve the purpose of simultaneous analysis of small molecule impurities and polymer impurities,and could better control the content of single impurities in the polymer,providing a reliable inspection basis for strict control of cefathiamidine quality.展开更多
The distinct influences of cephalosporins(CEPs, i.e., cefamandole nafate and cefpirome sulfate) affiliated to different generations on the volatile fatty acids(VFAs) production and antibiotic resistance genes(ARGs) fa...The distinct influences of cephalosporins(CEPs, i.e., cefamandole nafate and cefpirome sulfate) affiliated to different generations on the volatile fatty acids(VFAs) production and antibiotic resistance genes(ARGs) fates during waste activated sludge(WAS) fermentation were unveiled. The presence of CEPs mainly exhibited negative effects on the total VFAs production(5%–15% reduction), especially the cefamandole nafate, which is quite different to previous understanding. Further investigation revealed that the CEPs contributed to the solubilization and hydrolysis but inhibited the acidification process by affecting the functional microbial populations(i.e., Tissierella) and general microbial metabolic activities(i.e., pyruvate metabolism and VFAs biosynthesis). In addition, CEPs(especially the cefpirome sulfate)caused the propagation of ARGs(i.e., bla TEM, tet X and mex F) during WAS fermentation. CEPs enhanced the cell membrane permeability to promote the antibiotics mechanism of efflux pump and the horizontal transfer of ARGs. Also, the CEPs altered the regulatory systems(i.e., two component system) and microbial populations associated with ARGs, resulting in the proliferation of specific ARGs. Overall, the dissimilarity of different CEPs impacts on the WAS fermentation for VFAs production and ARGs variations enlightened the diverse environmental behaviors of anthropogenic pollutants and evoked the caution of ecological risks.展开更多
文摘We retrospectively evaluated the efficacy and safety of the combination drug piperacillin/tazobactam (PIPC/TAZ) in comparison with those of fourth-generation cephalosporins (4th Cephs) as initial empirical treatment in hematological malignancies patients with febrile neutropenia (FN). Among 200 patients assessed in this study, 49 had received PIPC/TAZ and 151 4th Cephs. Patient background characteristics were comparable between the two treatment groups. The overall efficacy rate in those receiving 4th Cephs and PIPC/TAZ was 57.0% (86/151 patients) and 59.2% (29/49 patients), respectively, with no significant difference detected between the two treatment regimens (P = 0.78). Treat-ment did not need to be discontinued or interrupted due to development of adverse drug reactions in any of the patients. Therefore in this study the efficacy and safety of PIPC/TAZ as initial antimicrobial treatment for FN in patients with hematological malignancies were not inferior to those of 4th Cephs. Based on the preliminary data obtained in this study, we propose to conduct a multicenter, prospective, controlled study to compare PIPC/TAZ versus CFPM given as empirical antimicrobial treatment against FN in patients with hematological malignancies.
文摘The accelerated weight gain in productive animals as a result of feeding antibiotic enriched fodder has been well known for decades. The better energy harvest is the result of modified gut microbiota as a consequence of applied antibiotics. Similar mechanisms might result obesity in humans as well. Objectives: Finding associations between global antibiotic consumption of different classes in EU countries and obesity data in adults and children prove that antibiotics might play a significant role in the development of obesity “epidemics” and related illnesses. Methods: Antibiotic consumption data were compared with obesity figures in adults and children in European countries and statistically analyzed for significance. Results: Significant correlation was found between the average yearly consumption of cephalosporins (p = 0.007), quinolones (p = 0.031), macrolides (p = 0.000083) and childhood obesity data, but no significant association was observed with the average penicillin consumption. No association was observed between adult obesity and any of the antibiotic classes studied. Conclusions: Our results support the hypothesis that different types of antibiotics might influence the development of obesity among children, and this finding can serve as a unified explanation for the development of obesity “epidemics”, similarly to the obesity and gut flora alteration-related diseases (type 2 diabetes mellitus, autism, etc.).
文摘In the present study we had an aim to develop the methods of functionalizing the surface of magnetite nanoparticles with cefotaxime and ceftriaxone antibiotics. The quantitative analysis of the nanostructured cephalosporins was determined by Atom Absorbance Spectroscopy (AAS) and based on the Lambert-Beer law. The engineered nanostructures were tested on gram-negative microorganisms Klebsiella spp., of Enterobacteriaceae, and gram-positive bacteria Staphylococcus aureus, each having multi-drug resistance properties.
文摘A simple, precise and accurate kinetic spectro-photometric method for determination of ce-fradine anhydrous, cefaclor monohydrate, ce-fadroxil monohydrate, cefalexin anhydrous and cefixime in bulk and in pharmaceutical formula-tions has been developed. The method based on a kinetic investigation of the reaction of the free carboxylic acid group of the drug with a mixture of potassium iodate and potassium iodide at room temperature to form yellow coloured triiodide ions. The reaction was followed up spectrophotometrically by measuring the increase in absorbance at 352 nm as a function of time. The initial rate, fixed time, variable time and rate-constant methods were adopted for constructing the calibration curves but fixed time method has been found to be more applicable. The analytical performance of the method, in terms of accuracy and precision, was statistically validated;the results were satisfactory. The method has been successfully applied to the determination of the studied drugs in commercial pharmaceutical formulations. Statistical comparison of the results with a well established reported method showed excellent ag- reement and proved that there is no significant difference in the accuracy and precision.
文摘A simple, accurate and precise spectrophotometric method has been proposed for the determination of eleven cephalosporins, namely;cefaclor monohydrate, cefadroxil monohydrate, cefalexin anhydrous, cefradine anhydrous, cefotaxime sodium, cefoperazone sodium, ceftriaxone sodium, ceftazidime penthydrate, cefazolin sodium, cefixime and cefpodoxime pro- xetil in bulk drug and in pharmaceutical formulations. The method depends on hydrolysis of the studied drugs using 0.5M NaOH at 100°C and subsequent reaction of the formed sulfide ions with NBD-Cl (4-chloro-7-nitrobenzo-2-oxa-1, 3-diazole) to form a yellow-colored chromogen measured at 390 nm. Different variables affecting the reaction (e.g. NaOH concentration, hydrolysis time, NBD-Cl concentration and diluting solvent) were studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients (0.9990- 0.9999) were found in the range of 5-160 μg mL-1 for all studied drugs. The limits of assay detection and quantitiation ranged from 0.289 to 5.867 and from 0.878 to 17.778 μg mL-1;respectively. The accuracy and precision of the proposed method were satisfactory. The method was successfully applied for analysis of the studied drugs in their pharmaceutical formulations and the recovery percentages ranged from 96.6 to 103.5%.
文摘Theoretical insights elucidate a series of active phosphonate esters application in preparation of Cephalosporin antibiotics’ intermediate. The B3LYP/6-311+G(d,p) method was employed to obtain the stable equilibrium geometries including comparing to the AE-active ester. It was found that the Ethyl-aminothiazoly Loximate (AT) molecule fragment is almost planar sheet, but it is almost perpendicular to the plane of phosphoryl ester. Moreover, the calculated Mulliken atomic charge distribution and frontier molecular orbital analysis of these esters showed that the amino N atom connected to the Thiazole ring of the AT had the maximum negative charge, which suggested that this area had high molecular activity. The value of ΔEL-H was energy gap between EHOMO and ELUMO and indicated that compound 6a had high reaction activity. The theory calculation results can explain the reaction mechanism well and predict that the novel active phosphonate ester has a hopeful application prospect in preparation of Cephalosporin antibiotics’ intermediate.
文摘Five new cephalosporin compounds were designed and synthesized, and the antibacterial activities were evaluated by the standard serial 2-fold agar dilution method in vitro. The results showed that the activities of the compounds Ia and lb against ESBL E. coli and K. pneumoniae are comparable to those of Cefepime.
基金supported by grant from the National Department Public Benefit Research Foundation(General Administration of Quality Supervision,inspection and Quarantine of the People's Republicof China)(Grant No.2012104008)At the sametime,the authors would like to thank Prof Yi zeng Liang(Central South University,PR China)for freely providing us with CARS program。
文摘Two universal spectral ranges(4550-4100 cm^(-1) and 6190-5510 cm^(-1))for construction of quantitative models of homologous analogs of cephalosporins were proposed by evaluating theperformance of five spectral ranges and their combinations,using three data sets of cephalos-porins for injection,ie.,cefuroxime sodium,cetriaxone sodium and cefoperazone sodium.Subsequently,the proposed ranges were validated by using eight calibration sets of otherhomologous analogs of cephalosporins for injection,namely cefmenoxime hydrochloride,ceftezole sodium,cefmetazole,cefoxitin sodium,cefotaxime sodium,cefradine,cephazolin sodium and ceftizoxime sodium.All the constructed quantitative models for the eight kinds of cephalosporinsusing these universal ranges could fulill the requirements for quick quantification.After that,competitive adaptive reweighted sampling(CARS)algorithm and infrared(IR)-near infrared(NIR)two-dimensional(2D)correlation spectral analysis were used to determine the scientific basis of these two spectral ranges as the universal regions for the construction of quantitativemodels of cephalosporins.The CAR.S algorithm demonstrated that the ranges of 4550-4100 cm^(-1) and 6190-5510 cm^(-1) included some key wavenumbers which could be attributed to content changes of cephalosporins.The IR-NIR 2D spectral analysis showed that certain wavenumbersin these two regions have strong correlations to the structures of those cephalosporins that wereeasy to degrade.
文摘Nine new derivatives of 7 β - (5- methyl- 1- aryl- 1H-1, 2, 3- triazoly- 4- carboxamido) cephalosporins were synthesized by acylction of 7 β -amino group of 7-ACA, 7-ADCA and 7-ACT with 5 -methsyl- 1 -aryl- 1 H- 1,2,3-triazoly-4-formyl chloride. The structure of the compounds were confirmed by elementray analysis IR, HNMR and FAB-MS. Some of them showed significant antibacterial activity
文摘Introduction: Gonorrhoeae and antimicrobial resistance AMR of gonococci is a major health problem today, because emerged resistance to last line empirical treatment for gonorrhoeae cephalosporins in many countries is predictable to be untreatable disease in near future. WHO GASP, WHO GLASS and WHO’s global action plan on AMR recommends to expand nationally and internationally to collect data to monitor AMR of gonococci for public health policies. Objective: Our aim is to detect resistance of gonococci to Cepha- losporins and determine the most effective empirical treatment for un-com- plicated gonococcal urethritis in males in Egypt. Methods: We depended in our methodology on selected gonococci from male urethral discharge specimens on Thyer Martien medium;collected 33 isolates during three years from 2017 to 2020;used antibiotics with MIC according to international standards and measuring IZD according to antimicrobial susceptibility testing reference ranges in international standards. Results: By statistical studies, resistance to cephalosporins was as follows: Cephradine 97%, Cefaclor 87.9%, Cefoxitin 97%, Ceftriaxone 90.9% and 42.4% to Cefepime, that shows hetero-genecity in resistance inside cephalosporin group;while resistance to Macrolides group represented by Azithromycin and Tetracyclins group represented by Doxycycline was as follows: Azithromycin 39.4%, Doxycycilne 27.3%;finally fluoroquinolones, the most effective group, resistance, was as: Levofloxacin 15.2%, Ciprofloxacin 15.2% and Ofloxacin 24.2%. Conclusion: The most effective empirical treatment for uncomplicated gonococcal urethritis in males in EGYPT is Fluoroquinolone;especially Levofloxacin ranks first susceptibility as 78.8% and 15.2% resistance followed by Ciprofloxacin susceptibility as 69.7% and 15.2% resistance, finally Ofloxacin susceptibility as 66.7% and 24.2% resistance;for Ceftriaxone not more recommended in EGYPT as empirical treatment for uncomplicated gonococcal urethritis, it is susceptibility as 6.1% and 90.9% resistance;in addition, we can use combination therapy of Fluoroquinolones with Azithromycin or Doxycycline, whose susceptibility is 30.3% for Azithromycin and 42.4% for Doxycycycline, while resistance is 39.4% for Azithromycin and 27.3% for Doxycycline. It is worth noting that only Cefepime in Cephalosporins group represents 42.4% susceptibility and 42.4% resistance;in addition to the Carbapenems group, it represents as 42.4% susceptibility for Imipenem and 45.5% resistance, then 42.2% susceptibility for Meropenem and 48.5% resistance, which can play role in combination therapy.
文摘An approach of using molinspiration calculations and molecular docking on PBPs (penicillin-binding proteins) and certain β-lactamases is employed to predict the molecular properties, bioactivity and resistance of newer and reference cephalosporins. The previously synthesized cephalosporins 1-8 and reference cephalosporins were subjected to extensive evaluations by calculating the molecular properties, drug-likeness scores on the bases of Lipinski's rule and bioactivity prediction using the method of molinspiration web-based software. The TPSA (topological polar surface area), OH-NH interactions, n-violation and the molinspiration Log partition coefficient (miLogP) values were also calculated. The investigated cephalosporins were subjected to molecular docking study on PBPs (lpyy) and on β-lactamases produced by S. aureus, K. pneumonia, E. coil and P. auroginosa using 1-click-docking website. Molecular properties of 1-8 recorded higher "FPSA than cephalexin and were lower than the reference cephalosporins and do not fulfill the requirements for Lipinski's rule. Bioactivities of 1-8 were predicted to be less and their docking scores on PBPs were comparable to those of the reference cephalosporins, particularly ceftobiprole. The references recorded various docking scores on the above β-lactamases and as expected, cefiobiprole recorded the lowest scores on all β-lactarnases. Cephalosporins 1-8 recorded various docking scores on β-lactamases. Molecular docking studies on PBPs and β-lactamases are considered as very useful, reliable and practical approach for predicting the bioactivity scores and to afford some information about the stability and selectivity of the newly proposed cephalosporins against β-lactamases of certain pathogenic microbes, such as P. auroginosa and MRSA, by recording the relative docking scores in comparison with those of reference cephalosporins.
基金supported by National Science and Technology Major Project(No.2018ZX10101001-004-003)Jiangsu Provincial high level health personnel"six one project"top talent project(No.LGY2019091)
文摘Objective:An increasing level of antimicrobial resistance to extended-spectrum cephalosporins has been reported,so we conducted this study to investigate the molecular characteristics of cephalosporin resistant Neisseria gonorrhoeae(NG)strains isolated from China Gonococcal Antimicrobial Resistance Surveillance Programme(China-GRSP).Methods:In total,2,038 NG isolates were collected from the China-GRSP between 2015 and 2016.NG multiantigen sequence typing(NG-MAST),multilocus sequence typing(MLST),and NG sequence typing for antimicrobial resistance(NG-STAR)were used to determine characteristics and resistant determinants of cephalosporin-resistant isolates.The results are described as percentages.Results:Seventy-four(3.6%)cephalosporin-resistant isolates were confirmed.MLST_(ST7363)was the most prevalent MLST among cefixime-resistant(CFX-R)isolates,whereas MLST_(ST7365)(n=8)in was the most prevalent sequence type among ceftriaxone-resistant(CRO-R)isolates.CFX-R strains were mainly associated with penA-X(n=27,44.3%),penA-XIII(n=6,9.8%),penA-XVIII(n=5,8.2%),and CRO-R strains were mainly related to penA-XVIII(n=10,25.6%),penA-43(n=9,23.1%),penA-XIII(n=7,17.9%).Conclusion:The main conclusion of this study is that the predominant cephalosporin-resistant clones in China include locally emerged and imported linages.The CFX-R and CRO-R strains are primarily related to penA mutations,and their predominant genotypes are different.With the increase in international travel,tracking high-risk-resistant clones and identifying outbreaks and their associations with epidemiological characteristics are critical to improve public health.
基金Supported by2023 Central Funds for Guiding Local Science and Technology Development(ZY20230102)Guilin City Scientific Research and Technology Development Plan Project(20220104-4).
文摘[Objectives]To establish a HPLC-MS method for the determination of polymer impurities in cefathiamidine and its preparations.[Methods]Kromasil 100-5 C_(18) column(4.6 mm ×250 mm,5μm)was used for analysis;mobile phase ammonium acetate solution(pH 6.30)-acetonitrile,gradient elution;volumetric flow rate 1.0 mL/min;column temperature 40℃;multi-reaction monitoring mode was used for analysis,and positive ion scanning was chosen as the electrospray ion source.[Results]The resolution between impurities and main peaks under this method was greater than 1.5,and 8 known impurities and 2 polymer impurities could be completely separated and distinguish-ed.It was inferred that the molecular ion peak[M+H]^(+):m/z727.1874,m/z 785.1937 was the possible polymer impurity of this product.[Conclusions]A method for the analysis of polymer impurities in cefathiamidine and its preparations was formed,which could achieve the purpose of simultaneous analysis of small molecule impurities and polymer impurities,and could better control the content of single impurities in the polymer,providing a reliable inspection basis for strict control of cefathiamidine quality.
基金financially supported by the National Natural Science Foundation of China (No. 52070069)Jiangsu Province Natural Science Foundation (No. BK20211207)+2 种基金China Postdoctoral Science Foundation (No. 2021M692423)Shanghai Post-doctoral Excellence Program (No. 2020419)the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD),China。
文摘The distinct influences of cephalosporins(CEPs, i.e., cefamandole nafate and cefpirome sulfate) affiliated to different generations on the volatile fatty acids(VFAs) production and antibiotic resistance genes(ARGs) fates during waste activated sludge(WAS) fermentation were unveiled. The presence of CEPs mainly exhibited negative effects on the total VFAs production(5%–15% reduction), especially the cefamandole nafate, which is quite different to previous understanding. Further investigation revealed that the CEPs contributed to the solubilization and hydrolysis but inhibited the acidification process by affecting the functional microbial populations(i.e., Tissierella) and general microbial metabolic activities(i.e., pyruvate metabolism and VFAs biosynthesis). In addition, CEPs(especially the cefpirome sulfate)caused the propagation of ARGs(i.e., bla TEM, tet X and mex F) during WAS fermentation. CEPs enhanced the cell membrane permeability to promote the antibiotics mechanism of efflux pump and the horizontal transfer of ARGs. Also, the CEPs altered the regulatory systems(i.e., two component system) and microbial populations associated with ARGs, resulting in the proliferation of specific ARGs. Overall, the dissimilarity of different CEPs impacts on the WAS fermentation for VFAs production and ARGs variations enlightened the diverse environmental behaviors of anthropogenic pollutants and evoked the caution of ecological risks.