BACKGROUND Pediatric perforated appendicitis(PPA)is a severe acute condition requiring surgical intervention and postoperative antibiotic therapy.Antibiotic selection differs significantly among pediatric centers,and ...BACKGROUND Pediatric perforated appendicitis(PPA)is a severe acute condition requiring surgical intervention and postoperative antibiotic therapy.Antibiotic selection differs significantly among pediatric centers,and an ideal postoperative antiinfective approach for PPA management has yet to be established.AIM To examine the spectrum of pathogenic bacteria in pediatric PPA and to summarize the postoperative experience with carbapenem(CBP)and cephalosporin(CPS)antibiotics.METHODS We retrospectively analyzed medical records of 65 children(43 boys,22 girls;mean age 6.92±3.41 years)with PPA who underwent surgery at our hospital between December 2019 and August 2022.Data were collected in September 2023.Based on postoperative antibiotic selection,patients were divided into CBP(32 cases)and CPS(33 cases)groups.Chi-square and T-tests compared recovery outcomes,while univariate and multivariate regression models identified independent factors affecting postoperative recovery.RESULTS There were no significant differences between the two groups in gender,age,weight,height,body mass index,baseline ear temperature,or heart rate(P>0.05).Escherichia coli(40.00%)and Pseudomonas aeruginosa(24.62%)were the most common pathogens in PPA.Postoperative analysis showed significantly shorter C-reactive protein(CRP)recovery times in the CPS group than in the CBP group[(6.18±1.84)vs(8.12±3.48)days,P=0.009].Univariate logistic regression indicated CPS selection(OR=0.32,95%CI:0.10-0.97,P=0.044)was significantly associated with a higher CRP recovery rate within 7 days.Multivariate analysis confirmed CPS selection(OR=3.49,95%CI:1.19-10.24,P=0.023)as an independent factor affecting CRP recovery within 7 days postoperatively.CONCLUSION The choice of CBP or CPS independently affects CRP recovery within 7 days.CBP offers no advantage over CPS in treating PPA,with CPS also demonstrating favorable clinical outcomes.展开更多
The latest progress in the process optimization and stability improvement of third-generation cephalosporins in recent years was reviewed.The introduction of green chemistry,enzyme catalysis,nanotechnology,lyophilizat...The latest progress in the process optimization and stability improvement of third-generation cephalosporins in recent years was reviewed.The introduction of green chemistry,enzyme catalysis,nanotechnology,lyophilization,and nitrogen-filled packaging technologies can only improve production efficiency and reduce the generation of by-products,but also significantly extend the shelf life of drugs.In the future,process automation and intelligent technology will further optimize the large-scale production process,and the combination of nanotechnology and precision drug delivery will promote the improvement of effect in clinical applications.展开更多
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
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
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
[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
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: this paper aims to explore the adverse reactions caused by the combined use of cephalosporins and a variety of western drugs, record relevant data in detail, and draw a conclusion through comparative analys...Objective: this paper aims to explore the adverse reactions caused by the combined use of cephalosporins and a variety of western drugs, record relevant data in detail, and draw a conclusion through comparative analysis. Methods: a total of 800 patients who received cephalosporins combined with a variety of western drugs in our hospital from January 2020 to March 2021 were randomly selected as the subjects of this study. The types of drugs and their compatibility as well as the incidence of adverse reactions before and after use were observed and recorded. The clinical manifestations and distribution types were summarized and discussed. Summarize data and make summary reports. Results: the incidence of adverse reactions was significantly higher after the combination of drug use than before. Most of adverse reactions were distributed in nervous system and digestive system. Compared with renal function and allergy, the incidence of adverse reactions was relatively low. The statistical analysis was cited, and the significance was established (P < 0. 05). Conclusions: the treatment of cephalosporin combined with a variety of western medicine to use effect significantly, and it can significantly shorten the patients' recovery time, reduce the chance to visit. But relatively adverse reactions occurred situation is more common and the reasons are complex. According to the analysis, due to improper use of drugs, non-standard production of drug manufacturers and disordered contraindication of related drugs, which will seriously affect the nervous and digestive system functions of patients, corresponding clinical attention should be paid attention to reduce the occurrence of such harmful events and achieve the harmonious development of doctor-patient relationship.展开更多
In filamentous fungi,nitrogen metabolism is repressed by GATA-type zinc finger transcription factors.Nitrogen metabolite repression has been found to affect antibiotic production,but the mechanism is still poorly unde...In filamentous fungi,nitrogen metabolism is repressed by GATA-type zinc finger transcription factors.Nitrogen metabolite repression has been found to affect antibiotic production,but the mechanism is still poorly understood.AcareB,encoding a homologue of fungal GATA-type regulatory protein,was cloned from Acremonium chrysogenum.Gene disruption and genetic complementation demonstrated that AcareB plays a key role in utilization of ammonium,glutamine and urea.In addition,significant reduction of cephalosporin production in the AcareB disruption mutant indicated that AcareB is important for cephalosporin production.In consistence with it,the transcriptional level of cephalosporin biosynthetic genes was significantly decreased in the AcareB disruption mutant.Electrophoretic mobility shift assay showed that AcAREB directly bound to the intergenic regions of pcbAB-pcbC,cefD1-cefD2 and cefEF-cefG.Sequence analysis showed that all the AcAREB binding sites contained the consensus GATA elements.AcareB is negatively autoregulated during cephalosporin production.Moreover,another GATA zinc-finger protein encoded by AcareA positively regulates the transcription of AcareB.However,AcareB does not regulate the transcription of AcareA.These results indicated that AcAREB plays an important role in both regulation of nitrogen metabolism and cephalosporin production in A.chrysogenum.展开更多
This paper describes a kinetic spectrophotometric method for simultaneous determination of three cephalosporin antibiotics,cephradine,cefaclor and cefixime,with the aid of chemometrics. The method relies on their oxid...This paper describes a kinetic spectrophotometric method for simultaneous determination of three cephalosporin antibiotics,cephradine,cefaclor and cefixime,with the aid of chemometrics. The method relies on their oxidation with KMnO4 to produce green manganate with different kinetic rates in alkaline medium. The proposed method was successfully applied to a pharmacokinetic study of three cephalosporin antibiotics in rabbit plasma via intravenous injections. The results indicated that the amount of cephradine,cefaclor and cefixime were reduced rapidly in rabbit blood,showing clear dose-dependency and the half-life of cefixime (160 min) was longer than those of cephradine (60 min) and cefaclor (60 min).展开更多
Acremonium chrysogenum is an important filamentous fungus which produces cephalosporin C in industry.This review summarized the study on genetic engineering of Acremonium chrysogenum,including biosynthesis and regulat...Acremonium chrysogenum is an important filamentous fungus which produces cephalosporin C in industry.This review summarized the study on genetic engineering of Acremonium chrysogenum,including biosynthesis and regulation for fermentation of cephalosporin C,molecular techniques,molecular breeding and transcriptomics of Acremonium chrysogenum.We believe with all the techniques available and full genomic sequence,the industrial strain of Acremonium chrysogenum can be genetically modified to better serve the pharmaceutical industry.展开更多
基金Supported by Jiaxing Science and Technology Plan Project,No.2024AD30035.
文摘BACKGROUND Pediatric perforated appendicitis(PPA)is a severe acute condition requiring surgical intervention and postoperative antibiotic therapy.Antibiotic selection differs significantly among pediatric centers,and an ideal postoperative antiinfective approach for PPA management has yet to be established.AIM To examine the spectrum of pathogenic bacteria in pediatric PPA and to summarize the postoperative experience with carbapenem(CBP)and cephalosporin(CPS)antibiotics.METHODS We retrospectively analyzed medical records of 65 children(43 boys,22 girls;mean age 6.92±3.41 years)with PPA who underwent surgery at our hospital between December 2019 and August 2022.Data were collected in September 2023.Based on postoperative antibiotic selection,patients were divided into CBP(32 cases)and CPS(33 cases)groups.Chi-square and T-tests compared recovery outcomes,while univariate and multivariate regression models identified independent factors affecting postoperative recovery.RESULTS There were no significant differences between the two groups in gender,age,weight,height,body mass index,baseline ear temperature,or heart rate(P>0.05).Escherichia coli(40.00%)and Pseudomonas aeruginosa(24.62%)were the most common pathogens in PPA.Postoperative analysis showed significantly shorter C-reactive protein(CRP)recovery times in the CPS group than in the CBP group[(6.18±1.84)vs(8.12±3.48)days,P=0.009].Univariate logistic regression indicated CPS selection(OR=0.32,95%CI:0.10-0.97,P=0.044)was significantly associated with a higher CRP recovery rate within 7 days.Multivariate analysis confirmed CPS selection(OR=3.49,95%CI:1.19-10.24,P=0.023)as an independent factor affecting CRP recovery within 7 days postoperatively.CONCLUSION The choice of CBP or CPS independently affects CRP recovery within 7 days.CBP offers no advantage over CPS in treating PPA,with CPS also demonstrating favorable clinical outcomes.
基金Supported by the Funds from Central Government for Guiding Local Science and Technology Development(ZY20230102)Planning Project of Scientific Research and Technology Development in Guilin(20220104-4,20210202-1)Science and Technology Planing Project of Guangxi(Guike AB24010263).
文摘The latest progress in the process optimization and stability improvement of third-generation cephalosporins in recent years was reviewed.The introduction of green chemistry,enzyme catalysis,nanotechnology,lyophilization,and nitrogen-filled packaging technologies can only improve production efficiency and reduce the generation of by-products,but also significantly extend the shelf life of drugs.In the future,process automation and intelligent technology will further optimize the large-scale production process,and the combination of nanotechnology and precision drug delivery will promote the improvement of effect in clinical applications.
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.
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.
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.
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.
文摘Objective: this paper aims to explore the adverse reactions caused by the combined use of cephalosporins and a variety of western drugs, record relevant data in detail, and draw a conclusion through comparative analysis. Methods: a total of 800 patients who received cephalosporins combined with a variety of western drugs in our hospital from January 2020 to March 2021 were randomly selected as the subjects of this study. The types of drugs and their compatibility as well as the incidence of adverse reactions before and after use were observed and recorded. The clinical manifestations and distribution types were summarized and discussed. Summarize data and make summary reports. Results: the incidence of adverse reactions was significantly higher after the combination of drug use than before. Most of adverse reactions were distributed in nervous system and digestive system. Compared with renal function and allergy, the incidence of adverse reactions was relatively low. The statistical analysis was cited, and the significance was established (P < 0. 05). Conclusions: the treatment of cephalosporin combined with a variety of western medicine to use effect significantly, and it can significantly shorten the patients' recovery time, reduce the chance to visit. But relatively adverse reactions occurred situation is more common and the reasons are complex. According to the analysis, due to improper use of drugs, non-standard production of drug manufacturers and disordered contraindication of related drugs, which will seriously affect the nervous and digestive system functions of patients, corresponding clinical attention should be paid attention to reduce the occurrence of such harmful events and achieve the harmonious development of doctor-patient relationship.
基金supported by the National Natural Science Foundation of China(31670091 and 31470177)
文摘In filamentous fungi,nitrogen metabolism is repressed by GATA-type zinc finger transcription factors.Nitrogen metabolite repression has been found to affect antibiotic production,but the mechanism is still poorly understood.AcareB,encoding a homologue of fungal GATA-type regulatory protein,was cloned from Acremonium chrysogenum.Gene disruption and genetic complementation demonstrated that AcareB plays a key role in utilization of ammonium,glutamine and urea.In addition,significant reduction of cephalosporin production in the AcareB disruption mutant indicated that AcareB is important for cephalosporin production.In consistence with it,the transcriptional level of cephalosporin biosynthetic genes was significantly decreased in the AcareB disruption mutant.Electrophoretic mobility shift assay showed that AcAREB directly bound to the intergenic regions of pcbAB-pcbC,cefD1-cefD2 and cefEF-cefG.Sequence analysis showed that all the AcAREB binding sites contained the consensus GATA elements.AcareB is negatively autoregulated during cephalosporin production.Moreover,another GATA zinc-finger protein encoded by AcareA positively regulates the transcription of AcareB.However,AcareB does not regulate the transcription of AcareA.These results indicated that AcAREB plays an important role in both regulation of nitrogen metabolism and cephalosporin production in A.chrysogenum.
基金support from the National Natural Science Foundation of China (21065007)the State Key Labo-ratory of Food Science and Technology of Nanchang University (SKLF-MB-200807 & SKLF-TS-200919)
文摘This paper describes a kinetic spectrophotometric method for simultaneous determination of three cephalosporin antibiotics,cephradine,cefaclor and cefixime,with the aid of chemometrics. The method relies on their oxidation with KMnO4 to produce green manganate with different kinetic rates in alkaline medium. The proposed method was successfully applied to a pharmacokinetic study of three cephalosporin antibiotics in rabbit plasma via intravenous injections. The results indicated that the amount of cephradine,cefaclor and cefixime were reduced rapidly in rabbit blood,showing clear dose-dependency and the half-life of cefixime (160 min) was longer than those of cephradine (60 min) and cefaclor (60 min).
文摘Acremonium chrysogenum is an important filamentous fungus which produces cephalosporin C in industry.This review summarized the study on genetic engineering of Acremonium chrysogenum,including biosynthesis and regulation for fermentation of cephalosporin C,molecular techniques,molecular breeding and transcriptomics of Acremonium chrysogenum.We believe with all the techniques available and full genomic sequence,the industrial strain of Acremonium chrysogenum can be genetically modified to better serve the pharmaceutical industry.
