Comparative in vitro activity of Meropenem, Imipenem and Piperacillin/tazobactam against 1071 clinical isolates using 2 different methods: a French multicentre study

<p>Abstract</p> <p>Background</p> <p>Meropenem is a carbapenem that has an excellent activity against many gram-positive and gram-negative aerobic, facultative, and anaerobic bacteria. The major objective of the present study was to assess the <it>in vitro </it>activity of meropenem compared to imipenem and piperacillin/tazobactam, against 1071 non-repetitive isolates collected from patients with bacteremia (55%), pneumonia (29%), peritonitis (12%) and wound infections (3%), in 15 French hospitals in 2006. The secondary aim of the study was to compare the results of routinely testings and those obtained by a referent laboratory.</p> <p>Method</p> <p>Susceptibility testing and Minimum Inhibitory Concentrations (MICs) of meropenem, imipenem and piperacillin/tazobactam were determined locally by Etest method. Susceptibility to meropenem was confirmed at a central laboratory by disc diffusion method and MICs determined by agar dilution method for meropenem, imipenem and piperacillin/tazobactam.</p> <p>Results</p> <p>Cumulative susceptibility rates against <it>Escherichia coli </it>were, meropenem and imipenem: 100% and piperacillin/tazobactam: 90%. Against other <it>Enterobacteriaceae</it>, the rates were meropenem: 99%, imipenem: 98% and piperacillin/tazobactam: 90%. All <it>Staphylococci</it>, <it>Streptococci </it>and anaerobes were susceptible to the three antibiotics. Against non fermeters, meropenem was active on 84-94% of the strains, imipenem on 84-98% of the strains and piperacillin/tazobactam on 90-100% of the strains.</p> <p>Conclusions</p> <p>Compared to imipenem, meropenem displays lower MICs against <it>Enterobacteriaceae</it>, <it>Escherichia coli </it>and <it>Pseudomonas aeruginosa</it>. Except for non fermenters, MICs90 of carbapenems were <4 mg/L. Piperacillin/tazobactam was less active against <it>Enterobacteriaceae </it>and <it>Acinetobacter </it>but not <it>P. aeruginosa</it>. Some discrepancies were noted between MICs determined by Etest accross centres and MICs determined by agar dilution method at the central laboratory. Discrepancies were more common for imipenem testing and more frequently related to a few centres. Overall MICs determined by Etest were in general higher (0.5 log to 1 log fold) than MICs by agar dilution.</p

New polyaminoisoprenyl antibiotics enhancers against two multidrug resistant Gramnegative bacteria from Enterobacter and Salmonella species

International audienceA series consisting of new polyaminoisoprenyl derivatives were prepared in moderate to good chemical yields varying from 32 to 64% according two synthetic pathways: 1) using a titanium reductive amination reaction affording a 50/50 mixture of cis and trans isomers 2) a direct nucleophilic substitution leading to a stereoselective synthesis of the compounds of interest. These compounds were then successfully evaluated for their in vitro antibiotic enhancer properties against resistant Gram-negative bacteria of four antibiotics belonging to four different families. The mechanism of action against Enterobacter aerogenes of one of the most efficient of these chemosensitizing agents was precisely evaluated by using fluorescent dyes to measure outer-membrane permeability and to determine membrane depolarization. The weak cytotoxicity encountered led us to perform an in vivo experiment dealing with the treatment of mice infected with Salmonella Typhimurium and affording preliminary promising results in terms of tolerance and efficiency of the polyaminoisoprenyl derivative 5r / doxycycline combination