Impact of Genetic Diversity of Uropathogenic Escherichia coli and Klebsiella pneumoniae Strains on the Dissemination of Extended Spectrum Beta-Lactam Resistance Genes in Côte d’Ivoire

The increase and spread of bacterial resistance to extended-spectrum beta-lactam antibiotics are reported in many infections and are a real public health problem worldwide. Drug pressure is a factor that favors the emergence of a population of better adapted bacteria. However, there is no literature highlighting the genetic diversity and evolutionary structure of E. coli and K. pneumoniae in an environment with high selection pressure in Côte d’Ivoire. The objective of this study was to evaluate the genetic diversity of E. coli and K. pneumoniae strains circulating at the HKB Hospital in Abobo and at the Daloa Regional Hospital and its impact on the dissemination of extended spectrum beta-lactam resistance genes. A total of 39 strains isolated from the urinary tract of infected patients, including 30 strains of E. coli and 9 strains of K. pneumoniae were studied. A total of 39 strains isolated from the urinary tract of infected patients, including 30 strains of E. coli and 9 strains of K. pneumoniae were studied. From genomic DNA extracts, ESBL resistance genes were amplified by PCR and sequenced, in addition to genetic typing by ERIC-PCR. The data obtained were submitted to genetic and bioinformatics analyses. The results have shown a genetic diversity important in E. coli and K. pneumoniae with diversity indexs (SID) ranging from 0.5 to 0.77. The genetic structure of the bacterial species studied has shown a clonal distribution of strains with clones expressing TEM-9 and CTX-M-15 variants. Also, this clonal structure was correlated with the spread of resistance genes in E. coli and K. pneumoniae. The spread of resistant clones is a factor that might limit the fight against antibiotic resistance.

Association ofβ-lactam antimicrobial's exposure with carbapenem-resistant Pseudomonas aeruginosa infection:a cumulative meta-analysis

Background:Carbapenems are effective against severe Pseudomonas aeruginosa nosocomial infections.Therefore,carbapenem-resistant Pseudomonas aeruginosa is a serious public health threat.An understanding of the risk of inappropriate exposure to different antimicrobials in resistant Pseudomonas aeruginosa infection could help in elucidating the effective approach towards using antimicrobials in vulnerable patients with CRPA infection.Object:To investigate the association between exposure ofβ-lactam antimicrobials and CRPA infection relative to control patients.Methods:The MEDLINE/PubMed and OVID/Embase databases were used to search case-control and cohort studies in English language which reported antimicrobial exposure as risk factors for CRPA infection.The pooled odds ratios(OR)were calculated using a random-effect and fixed-effect model,and forest plots from a cumulative meta-analysis method were used to better show how pooled OR changed as updated evidence accumulated.Results:A total of 24 studies comprising 7039 participants were included for cumulative meta-analysis.A positive correlation was found between development of CRPA infection and exposure of beta-lactam antimicrobials:carbapenems(OR=7.60,95%CI:3.95 to 14.62,P<0.0001),imipenem(OR=9.81,95%CI:5.56 to 17.33),ampicillin(OR=1.86,95%CI:1.14 to 2.41),piperacillin(OR=2.82,95%CI:1.46 to 2.43),penicillins(OR=1.42,95%CI:0.90 to 2.24),cephalosporins(OR=1.88,95%CI:1.46 to 2.43)andβlactamase inhibitors(OR=1.96,95%CI:1.44 to 2.67).Further,exposure of other antimicrobial agents like quinolone(OR=2.35,95%CI:1.78 to 3.10),ciprofloxacin(OR=2.35,95%CI:1.66 to 3.95),aminoglycoside(OR=2.17,95%CI:1.60 to 2.95),amikacin(OR=3.11,95%CI:2.10 to 4.61),glycopeptides(OR=3.02,95%CI:1.92 to 4.75)and vancomycin(OR=3.26,95%CI:1.48 to 7.18),were also found to be positively associated with development of CRPA infection.Conclusions:Exposure of all kinds ofβ-lactams is significantly associated with development of carbapenemresistant Pseudomonas aeruginosa infection.These findings provide an impetus to take a more active approach while usingβ-lactam antimicrobials in patients with resistant Pseudomonas aeruginosa infections.

钯催化合成N-芳基-γ-胺基-γ-丁内酰胺类化合物

γ-丁内酰胺是很多具有生物活性、药物活性化合物的核心结构单元。已报道的由过渡金属催化,直接合成N-芳基-γ-胺基-γ-丁内酰胺类化合物的反应,存在必须使用过氧化物、操作不便的局限性。以10%(物质的量分数,下同)Pd/C为催化剂,将芳香胺和N-甲基吡咯烷酮在空气气氛下的二甲苯中于100℃反应24 h得到N-芳基-γ-胺基-γ-丁内酰胺类化合物(3a~3g),产率高达91%。经过核磁氢谱、碳谱和高分辨质谱分析,产物的结构得到确证。

Synthesis and Steric Structure of β-Lactam Derivatives of 2,4-Diaryl-2,3-dihydro-1,5-benzothiazepines

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.

Synthesis of Some New Spiro <i>β</i>-Lactams and Thiazolidinones Compounds Containing Sulfur Incorporating Quinon Compounds

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.

β-lactams抗生素在输液中的配伍及稳定性

讨论了β-内酰胺类一些常用的抗生素水溶液的 p H值 ,与选择的输液 p H值两者应基本相近 ,才能合理配伍。

Novel Method for the Enantioselective Synthesis of β-Lactams

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 a-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.

探讨肺炎克雷伯菌临床感染的护理方式及对β-lactams药物耐药性的主决定因素

目的:研究探讨肺炎克雷伯菌(本文以下使用英文简称"KNP")临床感染的护理方式及对药物耐药性的主决定因素。方法:2011年1月～2013年1月,于我院共选择110例患者作为研究对象。首先对患者实施积极的护理干预,以防止院内感染。之后对患者送检物实施β-lactams的活性测定以及细胞膜的通透性测定。结果:和敏感菌株比较,泛耐药菌株以及多重耐药的菌株β-内酰胺酶(本文以下使用英文简称"β-lactamase")的活性显著增多,差异具有统计学意义(P<0.05)。泛耐药菌株以及多重耐药的菌株两者的外膜的通透性相对于敏感菌株而言,具有显著的阻碍作用,差异具有统计学意义(P<0.05)。结论:合理护理,可有效防止医院院内感染。且β-lactamase的活性以及细胞外膜的通透性是KNP对β-lactams耐药性的主决定性因素,对抗生素药物的筛选具有一定的指导意义。

Highly Stereoselective Synthesis of trans-3-Chloro-β-lactams from Imines and Mixed Chloroacetyl and Nitroacetyl Chlorides

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.

Synthesis and Stereostructure of New β-Lactam Derivatives of1,5-Benzothiazepines

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.

Synthesis and Crystal Structure of an (N-Protected amino)-β-lactam Derivative of 1,5-Benzothiazepine

The title compound -(N-protected amino)--lactam (C36H33N2O5ClS), derivative of 1,5-benzothiazepine, was prepared by the reaction of 1,5-benzothiazepine 1 with (4R)- phenyloxazolidylacetyl chloride and characteized by X-ray diffraction analysis. The title compound crystallizes in orthorhombic system, space group P212121 with a=12.293(2), b=26.026(5), c=10.146(2)? V=3246.1?, Z=4, Dc=1.312g/cm3, Mr=641.15, F(000)=1344, μ= 0.228 mm1. The final R=0.0597 and wR=0.1165 for 3226 observed reflections with I ≥ 2?I). The crystal structure shows that the 4-phenyloxazolidyl and phenyl attached to C(8) and C(9) are in cis positions, and no trans product was discovered. So the cyclization to -lactam is stereospecific.

Synthesis and Steric Structure of 1, 5-Benzothiazepine-Phenyl-β-Lactams

1, 5-Benzothiazepines 1 react with phenylacetyl chloride to give the title compounds.The structures of these new compounds were confirmed by elemental analysis, ~1H NMR, ^(13)C NMRand MS spectroscopy, and their configuration (the mutual positions of the substituents relative to theβ-lactam ring) and conformation of the compounds were determined by X-ray crystal analysis.

Metallo-β-Lactamases:A Major Threat to Human Health

Antibiotic resistance is one of the most significant challenges facing global healthcare. Since the 1940s, antibiotics have been used to fight infections, initially with penicillin and subsequently with various derivatives including cephalosporins, carbapenams and monobactams. A common characteristic of these antibiotics is the four-memberedβ-lactam ring. Alarmingly, in recent years an increasing number of bacteria have become resistant to these antibiotics. A major strategy employed by these pathogens is to use Zn(II)-dependent enzymes, the metallo-β-lactamases (MBLs), which hydrolyse theβ-lactam ring. Clinically useful MBL inhibitors are not yet available. Consequently, MBLs remain a major threat to human health. In this review biochemical properties of MBLs are discussed, focusing in particular on the interactions between the enzymes and the functionally essential metal ions. The precise role(s) of these metal ions is still debated and may differ between different MBLs. However, since they are required for catalysis, their binding site may present an alternative target for inhibitor design.

Rapid Detection of β-lactam Antibiotic Residue in Milk Using Biolayer Interferometry

[ Objective] This study aimed to establish a high-sensitivity method for rapid detection of^-lactam antibiotic residue in milk. [Method] Based on bio- layer interferometry technology, ampicillin-BSA conjugate was fixed on the bottom of APS fiber optic biosensor probe through hydrophobic interaction and bound to 40 mn colloidal gold-labeled/3-1actam 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 immunechromatographic test strip in detection of β-1actam antibiotic residue in milk. Colloidal gold-labeled BLI method exhibited good speci- ficity and had no cross-reaction with 1 000 ng/ml aflatoxin M1, gentamicin, kanamycin, streptomycin, tylosin, chloromycetin and melamine. [Condusion] 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 antibiot- ics, but it is a simple and rapid qualitative detection method that can be used in rapid detection of β-1actam antibiotic residue in milk.

Analysis of Trends in Resistance to Fluoroquinolones and Extended Spectrum Beta-Lactams among <i>Salmonella</i>Typhi Isolates Obtained from Patients at Four Outpatient Clinics in Nairobi County, Kenya

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.

Identification and preliminary characterization of novel B3-type metallo-β-lactamases

Antibiotic resistance has emerged as a major global threat to human health. Among the strategies employed by pathogens to acquire resistance the use of metallo-β-lactamases (MBLs), a family of dinuclear metalloenzymes, is among the most potent. MBLs are subdivided into three groups (i.e. B1, B2 and B3) with most of the virulence factors belonging to the B1 group. The recent discovery of AIM-1, a B3-type MBL, however, has illustrated the potential health threat of this group of MBLs. Here, we employed a bioinformatics approach to identify and characterize novel B3-type MBLs from Novosphingobium pentaromativorans and Simiduia agarivorans. These enzymes may not yet pose a direct risk to human health, but their structures and function may provide important insight into the design and synthesis of a still elusive universal MBL inhibitor.

Unusual metallo-β-lactamases may constitute a new subgroup in this family of enzymes

Metallo-β-lactamases (MBLs) are a family of Zn2+-dependent enzymes that have contributed strongly to the emergence and spread of antibiotic resistance. Novel members as well as variants of existing members of this family are discovered continuously, compounding their threat to global health care. MBLs are divided into three subgroups, i.e. B1, B2 and B3. The recent discovery of an unusual MBL from Serratia proteamaculans (SPR-1) suggests the presence of an additional subgroup, i.e. B4. A database search reveals that SPR-1 has only one homologue from Cronobacter sakazakii, CSA-1.These two MBLs have a unique active site and may employ a mechanism distinct from other MBLs, but reminiscent of some organophosphate-degrading hydrolases.

Resistance of Klebsiella to Imipenem by Production of Carbapenemase Gene blaIMP at Centre Hospitalier Universitaire Pédiatrique Charles de Gaulle, Ouagadougou, Burkina Faso

Objective: Class B carbapenemases are bacterial enzymes that catalyze the hydrolysis of β-lactam core antibiotics, except for monobactams. The objective of this study was to identify the carbapenemase gene blaIMP in the genus Klebsiella at the Charles De Gaulle Pediatric University Hospital (CHUP-CDG) of Ouagadougou, Burkina Faso. Methods: The study involved 17 bacterial strains responsible for human infection and isolated from various biological samples during the period from 2009 to 2013. The strains were tested for antimicrobial susceptibility to cefotaxime, ceftazidime and imipenem using the Mueller-Hinton agar diffusion method. The carbapenemases resistance genes were detected by conventional PCR using specific primers at the molecular biology laboratory of CERBA/LABIOGENE, Ouagadougou, Burkina Faso. Results: The antibiotic susceptibility test showed high resistance of the 17 Klebsiella isolates tested to cephalosporins. A high cefotaxime-resistance rate (82.35%) and ceftazidime-resistance rate (88.23%) was found among the strains tested against 11.76% resistance rate for imipenem. Analysis of PCR products by gel electrophoresis revealed 4 strains (23.53%) with blaIMP-type gene. Conclusion: Klebsiella is a well-known bacterium in clinical practice. The present study demonstrated the blaIMP-type gene in cephalosporin-resistant strains of Klebsiella at CHUP-CDG. More effective monitoring and treatment solutions are needed to prevent the spread of these resistant strains.

生物碱成分常用显色剂及一种检测内酰胺的特效方法

薄层层析 (TLC)中 ,碘化铋钾和改良碘化钾试剂常作为生物碱成分 (天然和合成化合物 )的显色剂。本文对它们进行综述、分析 ,以期对生物碱成分的薄层层析提供参考。同时提供一种检测γ 内酰胺的特效方法。

液相色谱-串联离子阱质谱测定牛奶中的12种β-内酰胺类药物残留的方法研究

This thesis developed a LC-ESI-TRAP-MS method for twelve β-lactam antibiotics residues in milk.The massspectrometer was operated in the positive ion mode using multiple reaction monitoring.The limit of detection is 1.0 and 2.0 μg/L.Overall recoveries were between 55.2% and 109.5%.