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.

Post-appendectomy pelvic abscess with extended-spectrum beta-lactamase producing Escherichia coli : A case report and review of literature

BACKGROUND Appendicitis, the inflammation of the appendix, is the most common abdominal surgical emergency requiring expedient surgical intervention. Extendedspectrum beta-lactamases(ESBLs) are bacterial enzymes that catalyse the degradation of the betalactam ring of penicillins and cephalosporins(but without carbapenemase activity), leading to resistance of these bacteria to beta-lactam antibiotics. Recent increases in incidence of ESBL-producing bacteria have caused alarm worldwide. Proportion estimates of ESBLEnterobacteriaceae hover around 46% in China, 42% in East Africa, 12% in Germany, and 8% in the United States.CASE SUMMARY The impact of ESBL-producing bacteria on appendiceal abscesses and consequent pelvic abscesses are yet to be examined in depth. A literature review using the search words "appendiceal abscesses" and "ESBL Escherichia coli(E. coli)" revealed very few cases involving ESBL E. coli in any capacity in the context of appendiceal abscesses. This report describes the clinical aspects of a patient with appendicitis whodeveloped a postoperative pelvic abscess infected with ESBL-producing E. coli. In this report, we discuss the risk factors for contracting ESBL E. coli infection in appendicitis and post-appendectomy pelvis abscesses. We also discuss our management approach for postappendectomy ESBL E. coli pelvic abscesses, including drainage, pathogen identification, and pathogen characterisation. When ESBL E. coli is confirmed, carbapenem antibiotics should be promptly administered, as was done efficaciously with this patient. Our report is the first one in a developed country involving ESBL E. coli related surgical complications in association with a routine laparoscopic appendectomy.CONCLUSION Our report is the first involving ESBL E. coli and appendiceal abscesses, and that too consequent to laparoscopic appendectomy.

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.

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.

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.

Synthesis, Crystal Structure and Antitumor Activities of 2-Acyl-β-lactam-2-carboxamides

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).

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。

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。

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.

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 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 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 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.

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.

Synthesis and Crystal Structure of α-( N-Protected a mino)β-lactam Derivative of 1 ,5-Benzothiazepine

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.

β-Lactam Templated Macrocyclization:Synthesis of 12-Membered Macrolide

A novel macrolactonization method was developed using a chiral β-lactam as the template. This novel method features that the macrocyclization is simultaneously achieved while a TBS protected hydroxy group is deprotected.

Synthesis and Crystal Structure of a β-Lactam Derivative of 2,4-Diaryl-1,5-Benzothiazepine

The compound(2) (C 24 H 20 NO 2ClS)(see Scheme 1) has been synthesized by reaction of 1, 5 benzothiazepine with chloroacetyl chloride and crystallized in the monoclinic system, space group P2 1/c, a=12.547(3), b=10.614(2), c=15.881(3) , β=105.91(3)°, V=2034.1(10) 3, D c =1.378 g/cm 3, Z=4, F(000)=880, μ (Mo Kα) =0.311 mm -1 , R= 0.0510 and R w =0.0647 for 1953 observed reflections. Structure analysis reveals that the cycloaddition to β lactam is stereospecific reaction, the chloro and phenyl substituents in four membered ring are located on the same side of the nucleus. The conformation of seven membered ring in compound (2) is chair like.