1,721,025 research outputs found

    Forthcoming therapeutic perspectives for infections due to multidrug-resistant Gram-positive pathogens

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    Multidrug resistance in Gram-positive pathogens emerged as a major therapeutic challenge over two decades ago. The worldwide spread of methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-resistant enterococci and other resistant Gram-positive pathogens had a major impact on antibiotic policies, and prompted the discovery and development of new antibiotics to combat difficult-to-treat infections caused by such pathogens. Several new antibiotics active against multidrug-resistant Gram-positive pathogens have recently been introduced into clinical practice, and the antibiotic pipeline contains additional anti-Gram-positive drugs at an advanced stage of development, including new glycopeptides (dalbavancin, oritavancin, and telavancin), new anti-MRSA beta-lactams (ceftobiprole), and new diaminopyrimidines (iclaprim). This article provides a brief overview of these upcoming agents, partially based on the material presented at the ESCMID Conference entitled 'Fighting infections due to multidrug-resistant Gram-positives' (Venice, Italy, 29-31 May 2008) and on the most recent literature

    Cloning and characterization of blaVIM, a new integron-borne metallo-beta-lactamase gene from a Pseudomonas aeruginosa clinical isolate

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    Production of a metallo-beta-lactamase activity was detected in a carbapenem-resistant Pseudomonas aeruginosa clinical isolate (isolate VR-143/97) from an Italian inpatient at the Verona University Hospital (northern Italy). The metallo-beta-lactamase determinant was isolated from a genomic library of VR-143/97, constructed in an Escherichia coli plasmid vector, by screening for clones with reduced susceptibility to imipenem. Sequencing of the cloned gene revealed that it encoded a new class B beta-lactamase that was named VIM-1. At the sequence level VIM-1 was rather divergent from the other class B enzymes (16.4 to 38.7% identity), overall being more similar to members of subclass B1 including the beta-lactamase II of Bacillus cereus (Bc-II), the Bacteroides fragilis CcrA, the Chryseobacterium meningosepticum BlaB, and the cassette-encoded IMP-1 enzymes. Among these, VIM-1 showed the highest degree of similarity to Bc-II. Similarly to blaIMP, blaVIM was also found to be carried on a gene cassette inserted into a class 1 integron. The blaVIM-containing integron was located on the chromosome of P. aeruginosa VR-143/97, and the metallo-beta-lactamase-encoding determinant was not transferable to E. coli by conjugation. Expression of the integron-borne blaVIM gene in E. coli resulted in a significant decrease in susceptibility to a broad array of beta-lactams (ampicillin, carbenicillin, piperacillin, mezlocillin, cefotaxime, cefoxitin, ceftazidime, cefoperazone, cefepime, and carbapenems), revealing a very broad substrate specificity of the VIM-1 enzyme

    Rapid access to pharmacokinetics data and correlation between antimicrobial susceptibility results and drug tissue distribution using a personal computer

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    MYMIC is a computer-aided system capable of integrating antibiotic susceptibility data with the concentrations the drugs reach in various body tissues and fluids by calculating site concentration/minimal inhibitory concentration quotients. The program can be run on any low-cost personal computer operating under MS-DOS, provided it is equipped with a hard-disk drive and with a minimum of 512 kilobytes of random access memory. The use of the program does not require any knowledge of computer languages. The antibiotic susceptibility data can be entered either as minimal inhibitory concentrations or as inhibitory zone diameters; in the latter case, minimal inhibitory concentrations are automatically calculated via regression formulas. The concentrations obtained by 90 antibiotics in 51 different human tissues and fluids are recorded in a data base of over 1,000 records, obtained from roughly 700 original papers. A MYMIC sample session was simulated by mimicking infections of three different body districts (namely bone, prostate, and sputum) caused by Pseudomonas aeruginosa, Escherichia coli or Providencia stuartii

    Double Synergy Differential Test for detection of plasmid-mediated AmpC-type beta-lactamases in Proteus mirabilis.

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    Proteus mirabilis resistant to expanded-spectrum cephalsoporins (ESC) is an emerging problem. In addition to extended-sectrum -lactamases (ESBLs), acquired AmpC-type -lactamases represent an important mechanism of resistance to ESC in P. mirabilis, at least in some countries. Distinction of clinical isolates producing an ESBL or an AmpC-type enzyme is a matter of interest for the implications in surveillance, infection control, and treatment issues. This work describes a simple and practical Double Synergy Differential Test (DSDT) that couples the detection of ESBLs and AmpC-type enzymes by means of a combo-disk approach using cefotaxime and ceftazidime as indicator substrates, and clavulanate and boronic acid as enzyme inhibitors. The DSDT was tested with a collection of 104 P. mirabilis with different beta-lactamase profiles, and proved to be highly sensitive and specific for the detection of ESBL- and AmpC-producing isolates
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