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a:5:{s:8:"template";s:1395:"<!DOCTYPE html> <html lang="en"> <head> <meta charset="utf-8"/> <meta content="width=device-width, initial-scale=1" name="viewport"/> <title>{{ keyword }}</title> </head> <style rel="stylesheet" type="text/css">@font-face{font-family:'Open Sans';font-style:normal;font-weight:400;src:local('Open Sans Regular'),local('OpenSans-Regular'),url(https://fonts.gstatic.com/s/opensans/v17/mem8YaGs126MiZpBA-UFVZ0e.ttf) format('truetype')}@font-face{font-family:'Open Sans';font-style:normal;font-weight:600;src:local('Open Sans SemiBold'),local('OpenSans-SemiBold'),url(https://fonts.gstatic.com/s/opensans/v17/mem5YaGs126MiZpBA-UNirkOUuhs.ttf) format('truetype')}</style> </head> <body class="wp-embed-responsive hfeed image-filters-enabled"> <div class="site" id="page"> <header class="site-header" id="masthead"> <div class="site-branding-container"> <div class="site-branding"> <p class="site-title"><h2>{{ keyword }}</h2></p> </div> </div> </header> <div class="site-content" id="content"> {{ text }} </div> <footer class="site-footer" id="colophon"> <aside aria-label="Footer" class="widget-area" role="complementary"> <div class="widget-column footer-widget-1"> <section class="widget widget_recent_entries" id="recent-posts-2"> <h2 class="widget-title">Recent Posts</h2> {{ links }} </section> </div> </aside> <div class="site-info"> {{ keyword }} 2021 </div> </footer> </div> </body> </html>";s:4:"text";s:6580:"© The Author 2014. We estimated the maximal kill rate constant, the parameters of a sigmoid-Emax effect model for each drug, and identify a parameter, α, that quantifies drug interaction. Small numbers of less susceptible isolates were recovered from levofloxacin-treated animals. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. 2003 Oct;47(2):427-30. doi: 10.1016/s0732-8893(03)00135-4. et al. All combination therapy arms generated near-maximal bacterial killing at less than maximal drug doses. The pharmacokinetic model included an ELF compartment, so the actual effect-site concentrations could be directly linked to the antibacterial effect observed. GL B, Bacterial population resistant to Mero. Lu The combination of meropenem plus levofloxacin was synergistic, producing good bacterial kill and resistance suppression. For mouse BAL fluid samples, an aliquot of 0.050 mL was diluted with 0.100 mL of HPLC water and analyzed. The levofloxacin humanization scheme was derived from earlier single-dose pharmacokinetic studies [6]. Current and future perspectives for levofloxacin in severe Pseudomonas aeruginosa infections. This combination attained 2-log killing 95.7% of the time in a 5000-subject simulation. Meropenem dosing as a single agent was 5, 8, 12.5, and 50 mg/kg every 4 hours. Neely For levofloxacin, doses indicated are daily doses. Epub 2019 Jun 12. The combination of meropenem plus levofloxacin was synergistic, producing good bacterial kill and resistance suppression. This leads to rapid bacterial clearance in the lungs of mice, which, for patients with pneumonia, hopefully translates to earlier extubation and transfer out of the intensive care unit. Jelliffe When α is negative and the upper bound of the 95% confidence interval does not cross 0, the interaction is statistically significantly antagonistic. An innovative combination-therapy analytic approach demonstrated that the combination was statistically significantly synergistic (α = 2.475), as was shown in the hollow fiber infection model. Greco The mean weighted error served as the measure of bias. 2010; 54(6):2646-54 (ISSN: 1098-6596) [Article in Japanese] Uoyama S(1), Kanda H, Yoshida K, Hoshino K. Author information: (1)Biological Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd. D'Argenio Measures of bias and precision were acceptable for all outputs. A Schumitzky Print 2018 Dec. See this image and copyright information in PMC. Would you like email updates of new search results? D . Drusano Mason All other FIC indices showed additive or P. aeruginosa strains but this rate dropped to … All animal experimentation was approved by the University of Florida Institutional Animal Care and Use Committee. This work was supported by the NIAID (grants R01AI079578 and RO1AI079729 to the Institute for Therapeutic Innovation). The range of the interday coefficient of variation was 3.63%–10.5% for plasma and 5.85%–9.77% for BAL fluid. For Permissions, please e-mail: journals.permissions@oup.com. The combination of meropenem and levofloxacin is synergistic with respect to both Pseudomonas aeruginosa kill rate and resistance suppression. Abbreviation: CFU, colony-forming units. There was also an untreated control group. Leary For mice that were treated with both antibiotics, tissue homogenates were quantitatively cultured onto agar plates supplemented with 3 times the MIC of meropenem and separate plates containing 3 times the MIC of levofloxacin. JC . P. aeruginosa strain PAO1 was a kind gift of Drs Bush and Queenan of Johnson & Johnson (Raritan, New York). Colistin sulfate produced a strong PAE ranging from 2.50 to 7.0 h in a concentration-dependent manner. Clear exposure responses were demonstrated for both meropenem alone and levofloxacin alone. . The second is to suppress the amplification of a resistant bacterial subpopulation. In our previous in vitro hollow fiber infection model (HFIM) study, this combination had a more rapid attainment of multilog cell killing than the monotherapies and completely suppressed the emergence of resistance over 14 days [1]. A dose-ranging study with meropenem and levofloxacin alone and in combination against Pseudomonas aeruginosa was performed in a granulocytopenic murine pneumonia model. We had previously studied the combination of meropenem and levofloxacin in our in vitro HFIM [1], where the regimen demonstrated great promise. Meropenem and levofloxacin were administered to partially humanize their pharmacokinetic profiles in mouse serum. The combination of meropenem and levofloxacin is synergistic with respect to both Pseudomonas aeruginosa kill rate and resistance suppression. aLevo was administered daily and not in a humanized fashion. The results revealed that combinations of colistin with other antibiotics could effectively inhibit colistin resistant isolates of K. pneumoniae, and thus could be further explore for the treatment of multidrug resistant pathogens. Anesthetized mice were infected via the intranasal route with 5 × 107 colony-forming units (CFU) of P. aeruginosa. Bravo Jelliffe A dose-ranging study with meropenem and levofloxacin alone and in combination against Pseudomonas aeruginosa was performed in a granulocytopenic murine pneumonia model. Clin Lab Med. All groups were analyzed simultaneously. The meropenem-levofloxacin combination exhibited a synergistic effect against one of five strains at 1 × MIC and two of five strains at 4 × MIC. 2020 Oct 20;64(11):e01610-20. An innovative combination-therapy analytic approach demonstrated that the combination was statistically significantly synergistic (α = 2.475), as was shown in the hollow fiber infection model. doi: 10.1128/AAC.01610-20. For sites where meropenem and levofloxacin have good susceptibility profiles, this combination may represent a reasonable choice. b Ellipses indicate that all support points had the same point estimates of the parameter values. The mean, median, and standard deviation of the pharmacodynamic parameter values are displayed in Table 3. 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