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dc.contributor.authorSteed, Molly E.
dc.contributor.authorVidaillac, Celine
dc.contributor.authorRybak, Michael J.
dc.date.accessioned2015-05-07T20:02:44Z
dc.date.available2015-05-07T20:02:44Z
dc.date.issued2011-07
dc.identifier.citationSteed, Molly E., Vidaillac, Celine, and Michael J. Rybak. "Evaluation of Ceftaroline Activity versus Daptomycin (DAP) against DAP-Nonsusceptible Methicillin-Resistant Staphylococcus aureus Strains in an In Vitro Pharmacokinetic/Pharmacodynamic Model." Antimicrob. Agents Chemother. July 2011 vol. 55 no. 7 3522-3526

http//:dx.doi.org/10.1128/AAC.00347-11
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dc.identifier.urihttp://hdl.handle.net/1808/17647
dc.descriptionThe authors have paid a fee to allow immediate free access to this article.en_US
dc.description.abstractThe objective of this study was to investigate the potential role of ceftaroline, a new broad-spectrum cephalosporin, as a therapeutic option for the treatment of daptomycin-nonsusceptible (DNS) methicillin-resistant Staphylococcus aureus (MRSA) infections. Four clinical DNS MRSA strains, R5717, R5563, R5996 (heteroresistant vancomycin-intermediate S. aureus) and R5995 (vancomycin-intermediate S. aureus) were evaluated in a two-compartment hollow-fiber in vitro pharmacokinetic/pharmacodynamic model at a starting inoculum of 107 CFU/ml for 96 h. Simulated regimens were ceftaroline at 600 mg every 12 h (q12h) (maximum free-drug concentration [fCmax], 15.2 μg/ml; serum half-life [t1/2], 2.3 h), daptomycin at 6 mg/kg q24h (fCmax, 7.9 μg/ml; t1/2, 8 h), and daptomycin at 10 mg/kg q24h (fCmax, 15.2 μg/ml; t1/2, 8 h). Differences in CFU/ml between 24 and 96 h were evaluated by analysis of variance with Tukey's post-hoc test. Bactericidal activity was defined as a ≥3-log10 CFU/ml decrease in the colony count from the initial inoculum. The ceftaroline MIC values were 0.25, 0.5, 0.5, and 0.5 μg/ml, and the daptomycin MIC values were 2, 2, 4, and 4 μg/ml for R5717, R5563, R5996, and R5995, respectively. Ceftaroline displayed sustained bactericidal activity against 3 of the 4 strains at 96 h (R5717, −3.1 log10 CFU/ml; R5563, −2.5 log10 CFU/ml; R5996, −5.77 log10 CFU/ml; R5995, −6.38 log10 CFU/ml). Regrowth occurred during the daptomycin at 6-mg/kg q24h regimen (4 strains) and the daptomycin at 10-mg/kg q24h regimen (3 strains). At 96 h, ceftaroline was significantly more active, resulting in CFU/ml counts lower than those obtained with daptomycin at 6 mg/kg q24h (4 strains, P ≤ 0.008) and daptomycin at 10 mg/kg q24 h (3 strains, P ≤ 0.001). Isolates with increased MIC values for daptomycin (all 4 strains) but not for ceftaroline were recovered. Ceftaroline was effective against the 4 isolates tested and may provide a clinical option for the treatment of DNS MRSA infections.en_US
dc.description.sponsorshipThis study was funded by a research grant from Forest Laboratories. Scientific Therapeutics Information, Inc. (Springfield, NJ), provided editorial assistance with the manuscript. Funding for editorial assistance was provided by Forest Laboratories, Inc. M.J.R. has received grant support, has served as a consultant, or has participated as a speaker for Astellas, Cerexa, Cubist, Forest, Pfizer, and Theravance. C.V. and M.E.S. have no conflicts of interest to declare.en_US
dc.publisherThe American Society for Microbiologyen_US
dc.titleEvaluation of Ceftaroline Activity versus Daptomycin (DAP) against DAP-Nonsusceptible Methicillin-Resistant Staphylococcus aureus Strains in an In Vitro Pharmacokinetic/Pharmacodynamic Modelen_US
dc.typeArticle
kusw.kuauthorSteed, Molly E.
kusw.kudepartmentDepartment of Pharmaceutical Chemistryen_US
dc.identifier.doi10.1128/AAC.00347-11
kusw.oaversionScholarly/refereed, publisher version
kusw.oapolicyThis item meets KU Open Access policy criteria.
dc.rights.accessrightsopenAccess


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