The Experts below are selected from a list of 300 Experts worldwide ranked by ideXlab platform
Nebojsa Janjic - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetic pharmacodynamic assessment of faropenem in a lethal murine bacillus anthracis inhalation postexposure prophylaxis model
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Stanley C. Gill, Ian A. Critchley, Christopher M. Rubino, Jennifer Bassett, Lynda Miller, Paul G. Ambrose, Sujata M. Bhavnani, Amber A. Beaudry, Kimberly Clawson Stone, Nebojsa JanjicAbstract:There are few options for prophylaxis after exposure to Bacillus anthracis, especially in children and women of childbearing potential. Faropenem is a -lactam in the penem subclass that is being developed as an oral prodrug, faropenem medoxomil, for the treatment of respiratory tract infections. Faropenem was shown to have in vitro activity against B. anthracis strains that variably express the bla1 -lactamase (MIC range, <0.06 to 1 g/ml). In this study we evaluated the pharmacokinetic-pharmacodynamic (PK-PD) relationships between the plasma faropenem free-drug (f) concentrations and efficacy against B. anthracis in a murine postexposure prophylaxis inhalation model. The plasma PKs and PKs-PDs of faropenem were evaluated in BALB/c mice following the intraperitoneal (i.p.) administration of doses ranging from 2.5 to 160 mg/kg of body weight. For the evaluation of efficacy, mice received by inhalation aerosol doses of B. anthracis (Ames strain; faropenem MIC, 0.06 g/ml) at 100 times the 50% lethal dose. The faropenem dosing regimens (10, 20, 40, and 80 mg/kg/day) were administered i.p. at 24 h postchallenge at 4-, 6-, and 12-h intervals for 14 days. The sigmoid maximum-threshold-of-efficacy (Emax) model fit the survival data, in which the free-drug area under the concentration-time curve (fAUC)/MIC ratio, the maximum concentration of free drug in plasma (fCmax)/MIC ratio, and the cumulative percentage of a 24-h period that the free-drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (f %TMIC) were each evaluated. Assessment of f %TMIC demonstrated the strongest correlation with survival (R 2 0.967) compared to the correlations achieved by assessment of fAUC/MIC or fCmax/MIC, for which minimal correlations were observed. The 50% effective dose (ED50), ED90, and ED99 corresponded to f %TMIC values of 10.6, 13.4, and 16.4%, respectively, and Emax was 89.3%. Overall, faropenem demonstrated a high level of activity against B. anthracis in the murine postexposure prophylaxis inhalation model.
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prevalence of serotype 19a streptococcus pneumoniae among isolates from u s children in 2005 2006 and activity of faropenem
Antimicrobial Agents and Chemotherapy, 2008Co-Authors: Ian A. Critchley, Michael R. Jacobs, Steven D Brown, Maria M Traczewski, Glenn S Tillotson, Nebojsa JanjicAbstract:Of 393 isolates of Streptococcus pneumoniae from U.S. children collected in 2005-2006, nonvaccine serotypes accounted for 89.1%, with serotype 19A the most prevalent, representing 30.5% of all isolates. The MIC90 of faropenem against serotype 19A isolates was 1 μg/ml, compared to ≥8 μg/ml against amoxicillin/clavulanate, cefdinir, cefuroxime axetil, and azithromycin.
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Prevalence of Serotype 19A Streptococcus pneumoniae among Isolates
2008Co-Authors: Glenn S Tillotson, Nebojsa JanjicAbstract:accounted for 89.1%, with serotype 19A the most prevalent, representing 30.5 % of all isolates. The MIC90 of faropenem against serotype 19A isolates was 1 g/ml, compared to>8 g/ml against amoxicillin/clavulanate, cefdinir, cefuroxime axetil, and azithromycin. Streptococcus pneumoniae continues to be a leading cause of respiratory tract infections in both children and adults (25). Although antimicrobial agents, such as the -lactams and mac-rolides, have been widely used to manage such infections, their success continues to be compromised by increasing resistance, especially among isolates from young children (20). An alter-native and attractive solution to the emergence of resistance has been the development and use of pneumococcal conjugate vaccines that would not only prevent a proportion of invasive pneumococcal disease (IPD), but also reduce the carriage of vaccine serotypes, including resistant phenotypes (31, 34). The heptavalent pneumococcal conjugate vaccine (PCV7) was ap
Ian A. Critchley - One of the best experts on this subject based on the ideXlab platform.
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Streptococcus pneumoniae, Haemophilus influenzae and
2015Co-Authors: Mark E. Jones, Ian A. Critchley, James A Karlowsky, Clyde Thornsberry, Renée S. Blosser-middleton, Daniel F. SahmAbstract:Activity of faropenem, a new furanem, against European respiratory pathogens collected during 2000–2001: a comparison with other β-lactam agent
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pharmacokinetic pharmacodynamic assessment of faropenem in a lethal murine bacillus anthracis inhalation postexposure prophylaxis model
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Stanley C. Gill, Ian A. Critchley, Christopher M. Rubino, Jennifer Bassett, Lynda Miller, Paul G. Ambrose, Sujata M. Bhavnani, Amber A. Beaudry, Kimberly Clawson Stone, Nebojsa JanjicAbstract:There are few options for prophylaxis after exposure to Bacillus anthracis, especially in children and women of childbearing potential. Faropenem is a -lactam in the penem subclass that is being developed as an oral prodrug, faropenem medoxomil, for the treatment of respiratory tract infections. Faropenem was shown to have in vitro activity against B. anthracis strains that variably express the bla1 -lactamase (MIC range, <0.06 to 1 g/ml). In this study we evaluated the pharmacokinetic-pharmacodynamic (PK-PD) relationships between the plasma faropenem free-drug (f) concentrations and efficacy against B. anthracis in a murine postexposure prophylaxis inhalation model. The plasma PKs and PKs-PDs of faropenem were evaluated in BALB/c mice following the intraperitoneal (i.p.) administration of doses ranging from 2.5 to 160 mg/kg of body weight. For the evaluation of efficacy, mice received by inhalation aerosol doses of B. anthracis (Ames strain; faropenem MIC, 0.06 g/ml) at 100 times the 50% lethal dose. The faropenem dosing regimens (10, 20, 40, and 80 mg/kg/day) were administered i.p. at 24 h postchallenge at 4-, 6-, and 12-h intervals for 14 days. The sigmoid maximum-threshold-of-efficacy (Emax) model fit the survival data, in which the free-drug area under the concentration-time curve (fAUC)/MIC ratio, the maximum concentration of free drug in plasma (fCmax)/MIC ratio, and the cumulative percentage of a 24-h period that the free-drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (f %TMIC) were each evaluated. Assessment of f %TMIC demonstrated the strongest correlation with survival (R 2 0.967) compared to the correlations achieved by assessment of fAUC/MIC or fCmax/MIC, for which minimal correlations were observed. The 50% effective dose (ED50), ED90, and ED99 corresponded to f %TMIC values of 10.6, 13.4, and 16.4%, respectively, and Emax was 89.3%. Overall, faropenem demonstrated a high level of activity against B. anthracis in the murine postexposure prophylaxis inhalation model.
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prevalence of serotype 19a streptococcus pneumoniae among isolates from u s children in 2005 2006 and activity of faropenem
Antimicrobial Agents and Chemotherapy, 2008Co-Authors: Ian A. Critchley, Michael R. Jacobs, Steven D Brown, Maria M Traczewski, Glenn S Tillotson, Nebojsa JanjicAbstract:Of 393 isolates of Streptococcus pneumoniae from U.S. children collected in 2005-2006, nonvaccine serotypes accounted for 89.1%, with serotype 19A the most prevalent, representing 30.5% of all isolates. The MIC90 of faropenem against serotype 19A isolates was 1 μg/ml, compared to ≥8 μg/ml against amoxicillin/clavulanate, cefdinir, cefuroxime axetil, and azithromycin.
Stanley C. Gill - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetic pharmacodynamic assessment of faropenem in a lethal murine bacillus anthracis inhalation postexposure prophylaxis model
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Stanley C. Gill, Ian A. Critchley, Christopher M. Rubino, Jennifer Bassett, Lynda Miller, Paul G. Ambrose, Sujata M. Bhavnani, Amber A. Beaudry, Kimberly Clawson Stone, Nebojsa JanjicAbstract:There are few options for prophylaxis after exposure to Bacillus anthracis, especially in children and women of childbearing potential. Faropenem is a -lactam in the penem subclass that is being developed as an oral prodrug, faropenem medoxomil, for the treatment of respiratory tract infections. Faropenem was shown to have in vitro activity against B. anthracis strains that variably express the bla1 -lactamase (MIC range, <0.06 to 1 g/ml). In this study we evaluated the pharmacokinetic-pharmacodynamic (PK-PD) relationships between the plasma faropenem free-drug (f) concentrations and efficacy against B. anthracis in a murine postexposure prophylaxis inhalation model. The plasma PKs and PKs-PDs of faropenem were evaluated in BALB/c mice following the intraperitoneal (i.p.) administration of doses ranging from 2.5 to 160 mg/kg of body weight. For the evaluation of efficacy, mice received by inhalation aerosol doses of B. anthracis (Ames strain; faropenem MIC, 0.06 g/ml) at 100 times the 50% lethal dose. The faropenem dosing regimens (10, 20, 40, and 80 mg/kg/day) were administered i.p. at 24 h postchallenge at 4-, 6-, and 12-h intervals for 14 days. The sigmoid maximum-threshold-of-efficacy (Emax) model fit the survival data, in which the free-drug area under the concentration-time curve (fAUC)/MIC ratio, the maximum concentration of free drug in plasma (fCmax)/MIC ratio, and the cumulative percentage of a 24-h period that the free-drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (f %TMIC) were each evaluated. Assessment of f %TMIC demonstrated the strongest correlation with survival (R 2 0.967) compared to the correlations achieved by assessment of fAUC/MIC or fCmax/MIC, for which minimal correlations were observed. The 50% effective dose (ED50), ED90, and ED99 corresponded to f %TMIC values of 10.6, 13.4, and 16.4%, respectively, and Emax was 89.3%. Overall, faropenem demonstrated a high level of activity against B. anthracis in the murine postexposure prophylaxis inhalation model.
Yu Chen - One of the best experts on this subject based on the ideXlab platform.
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molecular basis of substrate recognition and product release by the klebsiella pneumoniae carbapenemase kpc 2
Journal of Medicinal Chemistry, 2017Co-Authors: Orville A Pemberton, Xiujun Zhang, Yu ChenAbstract:Carbapenem-resistant Enterobacteriaceae are resistant to most β-lactam antibiotics due to the production of the Klebsiella pneumoniae carbapenemase (KPC-2) class A β-lactamase. Here, we present the first product complex crystal structures of KPC-2 with β-lactam antibiotics containing hydrolyzed cefotaxime and faropenem. They provide experimental insights into substrate recognition by KPC-2 and its unique cephalosporinase/carbapenemase activity. These structures also represent the first product complexes for a wild-type serine β-lactamase, elucidating the product release mechanism of these enzymes in general.
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Molecular Basis of Substrate Recognition and Product Release by the Klebsiella pneumoniae Carbapenemase (KPC-2)
2017Co-Authors: Orville A. Pemberton, Xiujun Zhang, Yu ChenAbstract:Carbapenem-resistant Enterobacteriaceae are resistant to most β-lactam antibiotics due to the production of the Klebsiella pneumoniae carbapenemase (KPC-2) class A β-lactamase. Here, we present the first product complex crystal structures of KPC-2 with β-lactam antibiotics containing hydrolyzed cefotaxime and faropenem. They provide experimental insights into substrate recognition by KPC-2 and its unique cephalosporinase/carbapenemase activity. These structures also represent the first product complexes for a wild-type serine β-lactamase, elucidating the product release mechanism of these enzymes in general
Christopher M. Rubino - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetic pharmacodynamic assessment of faropenem in a lethal murine bacillus anthracis inhalation postexposure prophylaxis model
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Stanley C. Gill, Ian A. Critchley, Christopher M. Rubino, Jennifer Bassett, Lynda Miller, Paul G. Ambrose, Sujata M. Bhavnani, Amber A. Beaudry, Kimberly Clawson Stone, Nebojsa JanjicAbstract:There are few options for prophylaxis after exposure to Bacillus anthracis, especially in children and women of childbearing potential. Faropenem is a -lactam in the penem subclass that is being developed as an oral prodrug, faropenem medoxomil, for the treatment of respiratory tract infections. Faropenem was shown to have in vitro activity against B. anthracis strains that variably express the bla1 -lactamase (MIC range, <0.06 to 1 g/ml). In this study we evaluated the pharmacokinetic-pharmacodynamic (PK-PD) relationships between the plasma faropenem free-drug (f) concentrations and efficacy against B. anthracis in a murine postexposure prophylaxis inhalation model. The plasma PKs and PKs-PDs of faropenem were evaluated in BALB/c mice following the intraperitoneal (i.p.) administration of doses ranging from 2.5 to 160 mg/kg of body weight. For the evaluation of efficacy, mice received by inhalation aerosol doses of B. anthracis (Ames strain; faropenem MIC, 0.06 g/ml) at 100 times the 50% lethal dose. The faropenem dosing regimens (10, 20, 40, and 80 mg/kg/day) were administered i.p. at 24 h postchallenge at 4-, 6-, and 12-h intervals for 14 days. The sigmoid maximum-threshold-of-efficacy (Emax) model fit the survival data, in which the free-drug area under the concentration-time curve (fAUC)/MIC ratio, the maximum concentration of free drug in plasma (fCmax)/MIC ratio, and the cumulative percentage of a 24-h period that the free-drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (f %TMIC) were each evaluated. Assessment of f %TMIC demonstrated the strongest correlation with survival (R 2 0.967) compared to the correlations achieved by assessment of fAUC/MIC or fCmax/MIC, for which minimal correlations were observed. The 50% effective dose (ED50), ED90, and ED99 corresponded to f %TMIC values of 10.6, 13.4, and 16.4%, respectively, and Emax was 89.3%. Overall, faropenem demonstrated a high level of activity against B. anthracis in the murine postexposure prophylaxis inhalation model.
