high protein binding and cidal activity against penicillin-resistant s. pneumoniae a cefditoren in vitro pharmacodynamic simulation高蛋白质绑定和cidal活动针对抗肺炎链球菌cefditoren体外药效学模拟.pdfVIP
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high protein binding and cidal activity against penicillin-resistant s. pneumoniae a cefditoren in vitro pharmacodynamic simulation高蛋白质绑定和cidal活动针对抗肺炎链球菌cefditoren体外药效学模拟
High Protein Binding and Cidal Activity against
Penicillin-Resistant S. pneumoniae: A Cefditoren In Vitro
Pharmacodynamic Simulation
1 1 1 ´ ´ ´ 1 ´ 1
David Sevillano , Lorenzo Aguilar *, Luis Alou , Marıa-Jose Gimenez , Natalia Gonzalez , Martha
1 1 ´ 2 3 ´ 1
Torrico , Fabio Cafini , Asuncion Fenoll , Pilar Coronel , Jose Prieto
1 Microbiology Department, School of Medicine, Universidad Complutense, Madrid, Spain, 2 Spanish National Reference Pneumococcal Laboratory, Instituto de Salud
Carlos III, Madrid, Spain, 3 Scientific Department, Tedec-Meiji Farma SA, Madrid, Spain
Abstract
Background: Although protein binding is a reversible phenomenon, it is assumed that antibacterial activity is exclusively
exerted by the free (unbound) fraction of antibiotics.
Methodology/Principal Findings: Activity of cefditoren, a highly protein bound 3rd generation cephalosporin, over 24h
after an oral 400 mg cefditoren-pivoxil bid regimen was studied against six S. pneumoniae strains (penicillin/cefditoren MICs;
mg/ml): S1 (0.12/0.25), S2 (0.25/0.25), S3 and S4 (0.5/0.5), S5 (1/0.5) and S6 (4/0.5). A computerized pharmacodynamic
simulation with media consisting in 75% human serum and 25% broth (mean albumin concentrations = 4.85 60.12 g/dL)
was performed. Protein binding was measured. The cumulative percentage of a 24h-period that drug concentrations
exceeded the MIC for total (T.MIC) and unbound concentrations (fT .MIC), expressed as percentage of the dosing interval,
were determined. Protein binding was 87.1%. Bactericidal activity ($99.9% initial inocula reduction) was obtained against
strains S1 and S2 at 24h (T.MIC = 77.6%, fT .MIC =
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