Microbiologic and Clinical Comparison of Patients Harboring <i>Escherichia coli</i>Blood Isolates with and without Extended-Spectrum <i>β</i>-Lactamases

The clinical and microbiologic characteristics of 34 patients with extended-spectrum β-lactamase (ESBL) positive E. coli isolated from blood were compared to 66 bacteremic patients with ESBL negative E. coli, from January 2007 through December 2009. Of the 21 ESBL positive isolates available for PCR analysis, 13 were positive for CTX-M, 8 for TEM, 4 for SHV β-lactamases, with 6 possessing multiple enzymes. Twenty of 34 (59%) ESBL-positive and 41 of 66 (62%) ESBL-negative blood isolates were considered community-associated. All but one isolate in both groups had MICs of ≤1.0 μg/ml to meropenem. However, when compared to ESBL-negative isolates, ESBL-positive isolates were more frequently resistant to levofloxacin, trimethoprim/sulfamethoxazole and had higher MICs to gentamicin, tobramycin and piperacillin/tazobactam. The use of intravenous and urinary catheters was strongly associated with the isolation of E. coli bloodstream isolates in both groups of patients. Although hospital stay was similar in both groups, appropriate therapy was given in 87% of patients with ESBL positive vs. 98% of patients with ESBL negative isolates and mortality was greater for patients with ESBL positive isolates (26% vs. 17%). Since a large proportion of E. coli blood isolates were ESBL-positive and community-associated, carbapenems should be considered as initial empiric therapy for such infections in our locale.

Antibiogram of Extended-Spectrum <i>β</i>-Lactamase (ESBL) Producing <i>Escherichia coli</i>

Background: Extended-spectrum β-lactamases (ESBLs) are enzymes capable of hydrolyzing extended-spectrum cephalosporins, penicillins and monobactams but inactive against cephamycins and carbapenems. The ESBL-producing organisms are a breed of multidrug-resistant pathogens. Objectives: This study was aimed to determine the susceptibility pattern of ESBL-producing Escherichia coli to ciprofloxacin, amikacin and imipenem. Methods: A total of 75 ESBL-producing E. coli, were obtained from the tertiary care hospitals of Bangladesh and were studied for susceptibility pattern from October, 2010 to December, 2011. These isolates were identified by double disc synergy test (DDST) and were confirmed phenotypically as ESBL-producer by phenotypic confirmatory disc diffusion test (PCDDT). Minimum inhibitory concentrations (MICs) of ciprofloxacin, amikacin and imipenem among ESBL-producing E. coli were determined using agar dilution method. Results: Out of 75 DDST positive ESBL-producing E. coli, 71 (94.67%) were also positive by PCDDT. All ESBL-producing E. coli, were susceptible to imipenem. About 92.95% ESBL-producing E. coli were susceptible to amikacin but only 14.08% were susceptible to ciprofloxacin. Conclusion: In this study, ESBL-producing E. coli, showed high resistance to ciprofloxacin. Imipenem and amikacin were most effective against ESBL positive strains.

Unravelling Antimicrobial Resistance Phenotypes and Carriage of Extended-Spectrum β-Lactamase Genes in Escherichia coli Isolated from Dairy Farms in Kiambu County, Kenya

The use of antibiotics for prophylaxis and growth enhancement in livestock farming is on the increase globally. This practice has led to the emergence and spread of antimicrobial-resistant bacteria in livestock. Only limited research has been done to establish the role of cattle farming in antimicrobial resistance. The current study sought to establish the carriage of multi-drug resistance and extended-spectrum beta-lactamase genes in Escherichia coli from farmers, their cattle, and cattle slurry within Kiambu County. A total of 286 (81%) E. coli isolates were recovered from 352 samples analysed. Antibiotic resistance profiles showed 114 (40%) isolates were resistant to ≥3 antimicrobial classes and were considered multidrug-resistant. Among multidrug-resistant (MDR) E. coli strains, 40 (14%) were resistant to 3 different antimicrobial classes, while 71 (25%) were resistant to between 4 and 7 antibiotic classes. Extended-spectrum β-lactamase resistance was found in 18 isolates: human (n = 14), cattle (n = 2), and environmental (n = 2). Both the blaCTX-M and blaTEM genes were detected in 10 and 15 strains, respectively. Sequence analysis showed that the isolates carried the blaTEM-116 (n = 7), blaTEM-1 (n = 5), and blaCTX-M-15 (n = 8) genes. Genotyping MDR isolates using (GTG) 5 PCR demonstrated that the isolates were not clonal. This data shows antimicrobial resistance profiles and different types of resistance genes in the E. coli population on dairy farms. As a result, more effective, targeted public health policies and measures need to be put in place to control and prevent the emergence and spread of resistant bacteria.

A novel LEN-derived β-lactamase from Klebsiela pneumoniae

β-lactam antibacterial agents are the most commonly used antibiotics in clinic. The production of β-lactamases is the important mechanism for resistance to β-lactam antibiotics in Gram-negative bacteria. As a result of the generous use of β-lactam antibiotics, mutations of β-lactamases gene in bacteria are frequently developed to oppose against attack from antibiotics, novel β-lactamases were found one after another, among them SHV-28, CTX-M-11 and CTX-M-22 β-lactamases were first found by Chinese researchers.

Effect of "Fuzheng Qingre Tonglin" prescription on rats with complicated urinary tract infection caused by ESBLs-producing Escherichia coli

Objective: To observe the effect of traditional Chinese medicine "Fuzheng Qingre Tonglin"prescription on rats with complicated urinary tract infection caused by extended-spectrumβ-lactamases (ESBLs)-producing Escherichia coli and its possible mechanism. Methods:Specific-pathogen-free female SD rats with 7-9 weeks old were randomly divided into model group, levofloxacin group, low-dose Fuzheng Qingre Tonglin group, high-dose Fuzheng Qingre Tonglin group, levofloxacin+Fuzheng Qingre Tonglin group (n=8 in each above group), and also there was a control group with 5 rats. Each group was administered intragastrically 2 days after model establishment for 14 consecutive days. The general condition of the rats was observed. Renal pathological changes were observed by light microscopy under hematoxylin-eosin staining. The number of white blood cells and the percentage of neutral particles (NEUT%) were detected. ELISA was used for the determination of C-reactive protein (CRP), CD4+, CD8+ in the blood, and secretory immunoglobulin A (SIgA), N-acetyl-β-D-glucosidase (NAG) molecules in urine. Results: There were a large number of inflammatory cells in the kidney of the model group and the levofloxacin group. The inflammatory cells in the treatment group were significantly reduced. The NEUT% and CRP in the blood of each treatment group and the NAG in the urine were significantly lower than those in the model group (P<0.05), except levofloxacin group. Compared with the model group, except for the levofloxacin group, serum CD4 concentration and CD4/CD8 ratio in the other treatment groups were significantly decreased, and CD8 molecules were significantly increased (P<0.05). Conclusion: "Fuzheng Qingre Tonglin" can alleviate systemic and local inflammation of complicated urinary tract infections in rats. It may also have the effect of re-sensing the insensitive antibacterial drug to bacteria and may have the function of regulating immune function and protecting kidney function in rats.

Insights on the structural characteristics of NDM-1: The journey so far

New Delhi metallo-β-lactamase (NDM-1) has created a medical storm ever since it was first reported;as it is active on virtually all clinically used β-lactam antibiotics. NDM-1 rampancy worldwide is now considered a nightmare scenario, particularly due to its rapid dissemination. An underlying theme in the majority of recent studies is structural characterization as knowledge of the three-dimensional structure of NDM-1 shall help find connections between its structure and function. Moreover, structural details are even critical in order to reveal the resistance mecha- nism to β-lactam antibiotics. In this perspective, we review structural characteristics of NDM-1 that have been delineated since its first report. We anticipate that these structure-function connections made by its characterization shall further serve as future guidelines for elucidating pathways towards de novo design of functional inhibitors.

Design, Synthesis, <i>in Vitro</i>Antibacterial Activity, and Docking Studies of New Rhodanine Derivatives

Bacterial infections present a serious challenge to healthcare practitioners due to the emergence of resistance to numerous conventional antibacterial drugs. Therefore, new bacterial targets and new antimicrobials are unmet medical needs. Rhodanine derivatives are known to possess potent antimicrobial activities. In this study, we determined the activity spectrum of a series of new rhodanine derivatives against representative Gram-positive and Gram-negative bacterial strains. Compounds 3a and 5a had the highest activity with minimum inhibitory concentrations in the range of 1.12 - 2.5 μg/mL. Transmission electron microscope results confirmed that activities against bacteria occurred via rupturing of the cell wall. Molecular modeling results suggested that rhodanine derivatives have the potential to irreversibly bind to the penicillin-binding protein (PBP) Ser62 residue in the active site. Thus, our results suggested that these rhodanine derivatives could be potential antibacterial drug candidates with strong activity against Gram-negative bacteria.

CTX-M-14, CTX-M-24 and resistance in Escherichia coli and Klebsiella pneumoniae clinical isolates

Extended-spectrum β-lactamases （ESBLs） are the main cause of resistance to the third and forth-generation cephalosporins in Enterobacteriaceae, which are mediated by plasmids and can hydrolyze oxyiminoaminothiazolyl cephalosporins and monobactams. Most of ESBLs are mutants of the classical TEM and SHV types, with one or more amino-acid substitution（s） in the active site.

Antimicrobial susceptibility of Gram-negative bacteria causing intra-abdominal infections in China： SMART China 2011

Background The Study for Monitoring Antimicrobial Resistance Trends program monitors the activity of antibiotics against aerobic and facultative Gram-negative bacilli （GNBs） from intra-abdominal infections （IAIs） in patients worldwide.Methods In 2011,1 929 aerobic and facultative GNBs from 21 hospitals in 16 cities in China were collected.All isolates were tested using a panel of 12 antimicrobial agents,and susceptibility was determined following the Clinical Laboratory Standards Institute guidelines.Results Among the Gram-negative pathogens causing IAIs,Escherichia coli （47.3％） was the most commonly isolated,followed by Klebsiella pneumoniae （17.2％）,Pseudomonas aeruginosa （10.1％）,and Acinetobacter baumannii （8.3％）.Enterobacteriaceae comprised 78.8％ （1521/1929） of the total isolates.Among the antimicrobial agents tested,ertapenem and imipenem were the most active agents against Enterobacteriaceae,with susceptibility rates of 95.1％ and 94.4％,followed by amikacin （93.9％） and piperacillin/tazobactam （87.7％）.Susceptibility rates of ceftriaxone,cefotaxime,ceftazidime,and cefepime against Enterobacteriaceae were 38.3％,38.3％,61.1％,and 50.8％,respectively.The leastactive agent against Enterobacteriaceae was ampicillin/sulbactam （25.9％）.The extended-spectrum β-lactamase （ESBL） rates among E.coli,K.pneumoniae,Klebsiella oxytoca,and Proteus mirabilis were 68.8％,38.1％,41.2％,and 57.7％,respectively.Conclusions Enterobacteriaceae were the major pathogens causing IAIs,and the most active agents against the study isolates （including those producing ESBLs） were ertapenem,imipenem,and amikacin.Including the carbapenems,most agents exhibited reduced susceptibility against ESBL-positive and multidrug-resistant isolates.