Background: β lactamase is a plasmid-encoded enzyme that hydrolyzes β lactam ring of β lactam antibiotics rendering them ineffective. These enzymes, produced by Staphylococcus aureus along with many other organisms...Background: β lactamase is a plasmid-encoded enzyme that hydrolyzes β lactam ring of β lactam antibiotics rendering them ineffective. These enzymes, produced by Staphylococcus aureus along with many other organisms, have hindered the use of many useful and once life-saving β lactam antibiotics from clinical practice. Methods: This study was aimed to compare three test methods-chromogenic, acidimetric and iodometric-for the detection of β lactamase enzyme produced by 404 nosocomial induced S. aureus isolated from two Nepali hospitals, Kathmandu based hospital (KBH) and Lalitpur based Hospital (LBH). The study was carried out following standard methodology during November 2007 to June 2009 in the Department of Microbiology, Institute of Medicine, Kathmandu, Nepal. Sensitivity, specificity, efficiency, positive predictive value, and negative predictive values of the tests were calculated taking penicillin resistance and sensitivity as the standard. Results: Chromogenic method was found to be the most sensitive (98.93%) and efficient (98.51%) test and had a high positive predictive value (99.46%). Sensitivity (98.4%) and efficiency (98.27%) of iodometric method was found to be comparable to chromogenic test;its specificity (96.55 %) and positive predictive value (99.73%) were the highest among the 3 tests. Acidimetric test was the least sensitive (97.33%) and efficient (96.78%). Of note, the sensitivity and specificity of these test methods have been compromised due to the negativity of few penicillin resistant isolates and positivity of some penicillin sensitive isolates, respectively. Conclusion: Chromogenic method was found comparatively to be the best test method for the detection of β lactamase production. However, in contrast to the other two test methods whose reagents can be locally and economically prepared, chromogenic test’s use has been impeded by its cost and unavailability in the local Nepali market.展开更多
包括青霉素在内的β-内酰胺类药物用于治疗A族链球菌(group A Streptococcus,GAS)感染已有80余年,虽然体外试验尚未发现对其耐药的GAS菌株,但自20世纪50年代以来,时有β-内酰胺类药物临床治疗GAS感染失败的报道。GAS体内耐受β-内酰胺...包括青霉素在内的β-内酰胺类药物用于治疗A族链球菌(group A Streptococcus,GAS)感染已有80余年,虽然体外试验尚未发现对其耐药的GAS菌株,但自20世纪50年代以来,时有β-内酰胺类药物临床治疗GAS感染失败的报道。GAS体内耐受β-内酰胺类药物的机制尚未明确。已有研究提示,GAS体内耐受β-内酰胺类药物与菌株对药物的敏感性降低、细菌的接种效应、生物膜的形成、共存菌的作用、细菌持留性及细菌可内化入胞内等因素有关。该文回顾总结了β-内酰胺类药物临床治疗GAS感染失败的主要报道,以及与GAS体内耐受β-内酰胺类药物机制相关的重要研究,为后续研究及临床用药提供参考。展开更多
The crystal of the title compound C, C 30 H 30 N 2O 3S has been prepared by reaction of 1,5 benzothiazepine with N protected glycine and determined by X ray single crystal diffraction. Crystal data: M r =498.62, tricl...The crystal of the title compound C, C 30 H 30 N 2O 3S has been prepared by reaction of 1,5 benzothiazepine with N protected glycine and determined by X ray single crystal diffraction. Crystal data: M r =498.62, triclinic with P 1 space group, a=10.880(2), b=13.955(3), c=9.537(2), α=99.34(3)°, β=110.43(3)°, γ=88 56(3)°, V=1338.2(5) 3, F(000)=528, λ (Mo Kα)=0.71073, Z=2, D c =1 237g/cm 3, μ =0.154mm -1 . Final R=0.0453, wR =0.1256 for 3491 observed reflections 〔 I>2σ(I) 〕. Structure analysis reveals that the substituents at C(23) and C(7) in four membered ring are located on the same side. The conformation of seven membered ring is chair like.展开更多
This paper reports the primary results of the study on β-lactam derivatives of 2,4-diaryl-2, 3-di hydro-1, 5 -benzothiazepines. Five titie compounds have been synthesized, and their configUration and conformation wer...This paper reports the primary results of the study on β-lactam derivatives of 2,4-diaryl-2, 3-di hydro-1, 5 -benzothiazepines. Five titie compounds have been synthesized, and their configUration and conformation were detendned by X-ray crystallographic analysis.展开更多
A series of 2-acyl-β-lactam-2-carboxamides was prepared through a tandem Ugi 4 CC/SN cyclization of bromoacetic acid, primary amine, arylglyoxal, and isocyanide. All of them were characterized by NMR, IR, MS and elem...A series of 2-acyl-β-lactam-2-carboxamides was prepared through a tandem Ugi 4 CC/SN cyclization of bromoacetic acid, primary amine, arylglyoxal, and isocyanide. All of them were characterized by NMR, IR, MS and elemental analysis. Meanwhile, the single crystal of compound 5 a, C_(19)H_(25)ClN_2 O_3, was also obtained and determined by X-ray crystallography. Crystal data: triclinic system, space group P_1, a = 8.1318(15), b = 11.931(2), c = 12.027(2) ?, α = 67.361(3)°, β = 73.009(3)°, γ = 85.663(3)°, V = 1029.1(3) ?3, Z = 2, F(000) = 388, Dc = 1.178 g/cm3, μ = 0.204 mm^(-1), R = 0.0786 and w R = 0.2212 for 3585 independent reflections(Rint = 0.0214) and 2960 observed ones(I > 2σ(I)). Intermolecular N–H···O stacking interactions contributed to the stability of the structure. The antitumor abilities of 5 were analyzed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo-liumbromide(MTT) standard method; 5 c stood out as the most potent showing an IC_(50) of 1.70 μmol/L against human tumor cell lines(HepG2).展开更多
A series of trans-3-chloro-β-lactams was synthesized stereospecifically from imines and chloroacetyl chloride or a mixture of chloroacetyl chloride and nitroacetyl chloride, prepared from vinylidene chloride and a mi...A series of trans-3-chloro-β-lactams was synthesized stereospecifically from imines and chloroacetyl chloride or a mixture of chloroacetyl chloride and nitroacetyl chloride, prepared from vinylidene chloride and a mixture of concentrated nitric acid and sulfuric acid, in the presence of triethylamine. The reaction of vinylidene chloride and the mixed acid was investigated. The formation mechanism of chloroacetyl chloride and nitroacetyl chloride and their reaction process with imines were proposed.展开更多
A novel method for the enantioselective synthesis of β-lactams is described in this study. 2,3-Dihydrobenzooxazin-4-one derived from salicylamide and L-menthone was used as the chiral auxiliary, which reacted with α...A novel method for the enantioselective synthesis of β-lactams is described in this study. 2,3-Dihydrobenzooxazin-4-one derived from salicylamide and L-menthone was used as the chiral auxiliary, which reacted with α-bromo-acyl bromides in the presence of pyridine to give carboximides 2. The stereo-controlled Reformatsky-type reactions of carboximides with imines yielded the corresponding trans β-lactams with high enantioselectivities(e.e. 75%―86%) and high chemical yields(63%―85%), meanwhile, the chiral auxiliary dihydrobenzooxazin-4-one was released and recovered.展开更多
Reaction of 1,5-benzothiazepine with N-protected glycine gives new a-amino-β-lactamderivatives of 1.5-benzothiazepine. The configuration and conformation of the products wereconfirmed by x-ray diffraction. The result...Reaction of 1,5-benzothiazepine with N-protected glycine gives new a-amino-β-lactamderivatives of 1.5-benzothiazepine. The configuration and conformation of the products wereconfirmed by x-ray diffraction. The result further reveals that the reaction of 1.5-benzothiazepineswith derivatives of carboxylic acid stereospecific.展开更多
[Objective]This study aimed to establish a high-sensitivity method for rapid detection of β-lactam antibiotic residue in milk. [Method]Based on biolayer interferometry technology,ampicillin-BSA conjugate was fixed on...[Objective]This study aimed to establish a high-sensitivity method for rapid detection of β-lactam antibiotic residue in milk. [Method]Based on biolayer interferometry technology,ampicillin-BSA conjugate was fixed on the bottom of APS fiber optic biosensor probe through hydrophobic interaction and bound to40 nm colloidal gold-labeled β-lactam antibiotic receptor,to detect β-lactam antibiotics in milk. [Result]The sensitivity of colloidal gold-labeled BLI method was twice as high as that of immunochromatographic test strip in detection of β-lactam antibiotic residue in milk. Colloidal gold-labeled BLI method exhibited good specificity and had no cross-reaction with 1 000 ng/ml aflatoxin M1,gentamicin,kanamycin,streptomycin,tylosin,chloromycetin and melamine. [Conclusion] The colloidal gold-labeled BLI method is not suitable for quantitative detection in actual production due to its small quantitative range in detection of β-lactam antibiotics,but it is a simple and rapid qualitative detection method that can be used in rapid detection of β-lactam antibiotic residue in milk.展开更多
Typhoid fever caused by the bacterium Salmonella enterica serovar Typhi (S. Typhi) causes an estimated 25 million illnesses and approximately 200,000 deaths annually mostly in developing countries. Although the manage...Typhoid fever caused by the bacterium Salmonella enterica serovar Typhi (S. Typhi) causes an estimated 25 million illnesses and approximately 200,000 deaths annually mostly in developing countries. Although the management of typhoid fever has been effectively through antibiotic treatment, S. Typhi is increasingly becoming resistant to the currently recommended drugs. This study utilized a quasi-experimental design focusing on archived samples to describe antimicrobial susceptibility patterns of S. Typhi and determine the genetic basis of resistance to the two most commonly used classes of antimicrobials. A total sample size of 287 isolates of S. Typhi isolates stored in -80°C freezer at the Centre for Microbiology Research was utilized. Isolates were subjected to anti-microbial susceptibility testing to commonly available antimicrobials using disk diffusion method, then analyzed for trends in resistance to fluoroquinolones and extended spectrum beta lactams. Among the 287 isolates 158 (55.5%) were found to be Multi Drug Resistant (MDR). This implied that these isolates were resistant to all first line classes of treatment such as ampicillin, chloramphenicol and sulfamethoxazole-trimethroprim. In addition to this, these isolates were also resistant to at least one of the currently recommended drugs of choice, either a β-lactam or a fluoroquinolone. This study observed resistances at 18.2% and 15.4% to fluoroquinolones and cephalosporins respectively. PCR results revealed presence of blaTEM, blaINT and blaCTX-M genes coding for resistance to β-lactams in 80% of the isolates that had combined resistance to β-lactams and fluoroquinolones. It is likely that recent heavy use of these classes of antimicrobials is driving resistances to these antimicrobials.展开更多
A series of spiro, β-Lactams, and thiazolidinones incorporating compounds 4 have been synthesized by cycloaddition reaction of, chloroacetyl chloride and mercaptoacetic acid with the synthesized Shiff,s bases 5a-c to...A series of spiro, β-Lactams, and thiazolidinones incorporating compounds 4 have been synthesized by cycloaddition reaction of, chloroacetyl chloride and mercaptoacetic acid with the synthesized Shiff,s bases 5a-c to give new spiro β- Lactam 6a-c and spiro thiazolidinone 7a-c the cycloaddition were characterized by spectral data including HNMR, 13C-NMR, IR and elemental analysis.展开更多
文摘Background: β lactamase is a plasmid-encoded enzyme that hydrolyzes β lactam ring of β lactam antibiotics rendering them ineffective. These enzymes, produced by Staphylococcus aureus along with many other organisms, have hindered the use of many useful and once life-saving β lactam antibiotics from clinical practice. Methods: This study was aimed to compare three test methods-chromogenic, acidimetric and iodometric-for the detection of β lactamase enzyme produced by 404 nosocomial induced S. aureus isolated from two Nepali hospitals, Kathmandu based hospital (KBH) and Lalitpur based Hospital (LBH). The study was carried out following standard methodology during November 2007 to June 2009 in the Department of Microbiology, Institute of Medicine, Kathmandu, Nepal. Sensitivity, specificity, efficiency, positive predictive value, and negative predictive values of the tests were calculated taking penicillin resistance and sensitivity as the standard. Results: Chromogenic method was found to be the most sensitive (98.93%) and efficient (98.51%) test and had a high positive predictive value (99.46%). Sensitivity (98.4%) and efficiency (98.27%) of iodometric method was found to be comparable to chromogenic test;its specificity (96.55 %) and positive predictive value (99.73%) were the highest among the 3 tests. Acidimetric test was the least sensitive (97.33%) and efficient (96.78%). Of note, the sensitivity and specificity of these test methods have been compromised due to the negativity of few penicillin resistant isolates and positivity of some penicillin sensitive isolates, respectively. Conclusion: Chromogenic method was found comparatively to be the best test method for the detection of β lactamase production. However, in contrast to the other two test methods whose reagents can be locally and economically prepared, chromogenic test’s use has been impeded by its cost and unavailability in the local Nepali market.
文摘包括青霉素在内的β-内酰胺类药物用于治疗A族链球菌(group A Streptococcus,GAS)感染已有80余年,虽然体外试验尚未发现对其耐药的GAS菌株,但自20世纪50年代以来,时有β-内酰胺类药物临床治疗GAS感染失败的报道。GAS体内耐受β-内酰胺类药物的机制尚未明确。已有研究提示,GAS体内耐受β-内酰胺类药物与菌株对药物的敏感性降低、细菌的接种效应、生物膜的形成、共存菌的作用、细菌持留性及细菌可内化入胞内等因素有关。该文回顾总结了β-内酰胺类药物临床治疗GAS感染失败的主要报道,以及与GAS体内耐受β-内酰胺类药物机制相关的重要研究,为后续研究及临床用药提供参考。
文摘The crystal of the title compound C, C 30 H 30 N 2O 3S has been prepared by reaction of 1,5 benzothiazepine with N protected glycine and determined by X ray single crystal diffraction. Crystal data: M r =498.62, triclinic with P 1 space group, a=10.880(2), b=13.955(3), c=9.537(2), α=99.34(3)°, β=110.43(3)°, γ=88 56(3)°, V=1338.2(5) 3, F(000)=528, λ (Mo Kα)=0.71073, Z=2, D c =1 237g/cm 3, μ =0.154mm -1 . Final R=0.0453, wR =0.1256 for 3491 observed reflections 〔 I>2σ(I) 〕. Structure analysis reveals that the substituents at C(23) and C(7) in four membered ring are located on the same side. The conformation of seven membered ring is chair like.
文摘This paper reports the primary results of the study on β-lactam derivatives of 2,4-diaryl-2, 3-di hydro-1, 5 -benzothiazepines. Five titie compounds have been synthesized, and their configUration and conformation were detendned by X-ray crystallographic analysis.
基金Financial support from the National Natural Science Foundation of China(No.81773746)the Open Project of Hubei Key Laboratory of Wudang Local Chinese Medicine Research,Hubei University of Medicine(No.WDCM009 and 2011JH-2014CXTT07)+1 种基金the Foundation of Health and Family planning Commission of Hubei Province(No.WJ2015Z113)the Foundation for Innovative Research Team of Hubei University of Medicine(2014CXZ01 and 2014CXZ05)
文摘A series of 2-acyl-β-lactam-2-carboxamides was prepared through a tandem Ugi 4 CC/SN cyclization of bromoacetic acid, primary amine, arylglyoxal, and isocyanide. All of them were characterized by NMR, IR, MS and elemental analysis. Meanwhile, the single crystal of compound 5 a, C_(19)H_(25)ClN_2 O_3, was also obtained and determined by X-ray crystallography. Crystal data: triclinic system, space group P_1, a = 8.1318(15), b = 11.931(2), c = 12.027(2) ?, α = 67.361(3)°, β = 73.009(3)°, γ = 85.663(3)°, V = 1029.1(3) ?3, Z = 2, F(000) = 388, Dc = 1.178 g/cm3, μ = 0.204 mm^(-1), R = 0.0786 and w R = 0.2212 for 3585 independent reflections(Rint = 0.0214) and 2960 observed ones(I > 2σ(I)). Intermolecular N–H···O stacking interactions contributed to the stability of the structure. The antitumor abilities of 5 were analyzed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo-liumbromide(MTT) standard method; 5 c stood out as the most potent showing an IC_(50) of 1.70 μmol/L against human tumor cell lines(HepG2).
基金Supported by the National Natural Science Foundation of China(Nos.20772005,20972013)the Beijing Natural Science Foundation,China(No.2092022)the Specialized Research Fund for the Doctoral Program of Higher Education,Ministry of Education of China
文摘A series of trans-3-chloro-β-lactams was synthesized stereospecifically from imines and chloroacetyl chloride or a mixture of chloroacetyl chloride and nitroacetyl chloride, prepared from vinylidene chloride and a mixture of concentrated nitric acid and sulfuric acid, in the presence of triethylamine. The reaction of vinylidene chloride and the mixed acid was investigated. The formation mechanism of chloroacetyl chloride and nitroacetyl chloride and their reaction process with imines were proposed.
基金National Natural Science Foundation of China(No. 20272051)Natural Science Foundation of Zhejiang Province, China(No. R404109)
文摘A novel method for the enantioselective synthesis of β-lactams is described in this study. 2,3-Dihydrobenzooxazin-4-one derived from salicylamide and L-menthone was used as the chiral auxiliary, which reacted with α-bromo-acyl bromides in the presence of pyridine to give carboximides 2. The stereo-controlled Reformatsky-type reactions of carboximides with imines yielded the corresponding trans β-lactams with high enantioselectivities(e.e. 75%―86%) and high chemical yields(63%―85%), meanwhile, the chiral auxiliary dihydrobenzooxazin-4-one was released and recovered.
文摘Reaction of 1,5-benzothiazepine with N-protected glycine gives new a-amino-β-lactamderivatives of 1.5-benzothiazepine. The configuration and conformation of the products wereconfirmed by x-ray diffraction. The result further reveals that the reaction of 1.5-benzothiazepineswith derivatives of carboxylic acid stereospecific.
基金Supported by International Science and Technology Cooperation Project of China(No.:2011DFA32930)"Twelfth Five-Year"National Science and Technology Support Program of China(No.:2012BAK17B10)
文摘[Objective]This study aimed to establish a high-sensitivity method for rapid detection of β-lactam antibiotic residue in milk. [Method]Based on biolayer interferometry technology,ampicillin-BSA conjugate was fixed on the bottom of APS fiber optic biosensor probe through hydrophobic interaction and bound to40 nm colloidal gold-labeled β-lactam antibiotic receptor,to detect β-lactam antibiotics in milk. [Result]The sensitivity of colloidal gold-labeled BLI method was twice as high as that of immunochromatographic test strip in detection of β-lactam antibiotic residue in milk. Colloidal gold-labeled BLI method exhibited good specificity and had no cross-reaction with 1 000 ng/ml aflatoxin M1,gentamicin,kanamycin,streptomycin,tylosin,chloromycetin and melamine. [Conclusion] The colloidal gold-labeled BLI method is not suitable for quantitative detection in actual production due to its small quantitative range in detection of β-lactam antibiotics,but it is a simple and rapid qualitative detection method that can be used in rapid detection of β-lactam antibiotic residue in milk.
文摘Typhoid fever caused by the bacterium Salmonella enterica serovar Typhi (S. Typhi) causes an estimated 25 million illnesses and approximately 200,000 deaths annually mostly in developing countries. Although the management of typhoid fever has been effectively through antibiotic treatment, S. Typhi is increasingly becoming resistant to the currently recommended drugs. This study utilized a quasi-experimental design focusing on archived samples to describe antimicrobial susceptibility patterns of S. Typhi and determine the genetic basis of resistance to the two most commonly used classes of antimicrobials. A total sample size of 287 isolates of S. Typhi isolates stored in -80°C freezer at the Centre for Microbiology Research was utilized. Isolates were subjected to anti-microbial susceptibility testing to commonly available antimicrobials using disk diffusion method, then analyzed for trends in resistance to fluoroquinolones and extended spectrum beta lactams. Among the 287 isolates 158 (55.5%) were found to be Multi Drug Resistant (MDR). This implied that these isolates were resistant to all first line classes of treatment such as ampicillin, chloramphenicol and sulfamethoxazole-trimethroprim. In addition to this, these isolates were also resistant to at least one of the currently recommended drugs of choice, either a β-lactam or a fluoroquinolone. This study observed resistances at 18.2% and 15.4% to fluoroquinolones and cephalosporins respectively. PCR results revealed presence of blaTEM, blaINT and blaCTX-M genes coding for resistance to β-lactams in 80% of the isolates that had combined resistance to β-lactams and fluoroquinolones. It is likely that recent heavy use of these classes of antimicrobials is driving resistances to these antimicrobials.
文摘A series of spiro, β-Lactams, and thiazolidinones incorporating compounds 4 have been synthesized by cycloaddition reaction of, chloroacetyl chloride and mercaptoacetic acid with the synthesized Shiff,s bases 5a-c to give new spiro β- Lactam 6a-c and spiro thiazolidinone 7a-c the cycloaddition were characterized by spectral data including HNMR, 13C-NMR, IR and elemental analysis.
