In vitro antimicrobial effects of aztreonam, colistin, and the 3-drug combination of aztreonam, ceftazidime and amikacin on metallo-β-lactamase-producing Pseudomonas aeruginosa

<p>Abstract</p> <p>Background</p> <p>There are limited choice of antimicrobial agents to treat infection with metallo-<it>β</it>-lactamase-producing <it>Pseudomonas aeruginosa</it>. We evaluate the antimicrobial effects of aztreonam alone, colistin alone and the 3-drug combination of aztreonam, ceftazidime and amikacin on 23 strains of metallo-<it>β</it>-lactamase-producing <it>P. aeruginosa </it>by time-killing tests.</p> <p>Methods</p> <p>Strains used were from different hospitals in Japan and had different pulse-field gel electrophoresis patterns by restriction with <it>Spe</it>I. The minimum inhibitory concentrations of 11 antimicrobial agents (piperacillin, piperacillin/tazobactam, imipenem, meropenem, aztreonam, ceftazidime, amikacin, tobramycin, arbekacin, ciprofloxacin and colistin) were determined using the agar dilution test. The effects of aztreonam, colistin and the combination of aztreonam, ceftazidime and amikacin were determined by time-killing studies.</p> <p>Results</p> <p>Bacteriostatic effects after 6 hours of drug exposure were observed in 12 strains (52.2%) of 23 strains of metallo-<it>β</it>-lactamase-producing <it>P. aeruginosa </it>with 48 mg/l aztreonam, in 19 strains (82.6%) with the 3-drug combination of 16 mg/l aztreonam, 16 mg/l ceftazidime, and 4 mg/l amikacin, and in 23 strains (100%) with 2 mg/l colistin. Bactericidal effects after 6 h drug exposure were observed in 1 strain (4.3%) with 48 mg/l aztreonam, in 8 strains (30.4%) with the 3-drug combination and in all 23 strains (100%) with 2 mg/l colistin.</p> <p>Conclusion</p> <p>Evaluation of <it>in vitro </it>antimicrobial effects on metallo-<it>β</it>-lactamase-producing <it>P. aeruginosa </it>revealed relatively good effects of the 3-drug combination of aztreonam, ceftazidime and amikacin and marked effects of colistin.</p

The Extracellular Matrix Component Psl Provides Fast-Acting Antibiotic Defense in Pseudomonas aeruginosa Biofilms

Bacteria within biofilms secrete and surround themselves with an extracellular matrix, which serves as a first line of defense against antibiotic attack. Polysaccharides constitute major elements of the biofilm matrix and are implied in surface adhesion and biofilm organization, but their contributions to the resistance properties of biofilms remain largely elusive. Using a combination of static and continuous-flow biofilm experiments we show that Psl, one major polysaccharide in the Pseudomonas aeruginosa biofilm matrix, provides a generic first line of defense toward antibiotics with diverse biochemical properties during the initial stages of biofilm development. Furthermore, we show with mixed-strain experiments that antibiotic-sensitive “non-producing” cells lacking Psl can gain tolerance by integrating into Psl-containing biofilms. However, non-producers dilute the protective capacity of the matrix and hence, excessive incorporation can result in the collapse of resistance of the entire community. Our data also reveal that Psl mediated protection is extendible to E. coli and S. aureus in co-culture biofilms. Together, our study shows that Psl represents a critical first bottleneck to the antibiotic attack of a biofilm community early in biofilm development.National Institutes of Health (U.S.). National Institute of Environmental Health Sciences (Training Grant in Toxicology 5 T32 ES7020-37

Expert consensus statements and summary of proceedings from the International Safety and Quality of Parenteral Nutrition Summit.

The International Safety and Quality of Parenteral Nutrition (PN) Summit consisted of presentations, discussions, and formulation of consensus statements. The purpose here is to briefly summarize the summit and to present the consensus statements. There was a high degree of consensus, with all statements approved by all authors/summit experts. These consensus statements should be regarded not as formal guidelines but rather as best-practice guidance intended to complement national and international nutrition society evidence-based guidelines and position statements. This article also summarizes key discussion topics from the summit, encompassing up-to-date knowledge and practical guidance concerning PN safety and quality in various countries and clinical settings, focusing on adult patients. Clear geographical differences exist between practices in Europe and the United States, and different approaches to improve the safety, quality, and cost-effectiveness of PN vary, particularly with regard to the delivery systems used. Discussion between experts allowed for an exchange of practical experience in optimizing PN use processes, opportunities for standardization, use of electronic systems, potential improvements in PN formulations, better management during PN component shortages, and practical guidance to address patients' needs, particularly during long-term/home PN. The consensus statements are the collective opinion of the panel members and form best-practice guidance. The authors intend that this guidance may help to improve the safety and quality of PN in a variety of settings by bridging the gap between published guideline recommendations and common practical issues