The Experts below are selected from a list of 807 Experts worldwide ranked by ideXlab platform
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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Pharmacokinetic-Pharmacodynamic Assessment of Faropenem in a Lethal Murine Bacillus anthracis Inhalation Postexposure Prophylaxis Model
Antimicrobial agents and chemotherapy, 2010Co-Authors: Stanley C. Gill, Christopher M. Rubino, Jennifer Bassett, Lynda Miller, Paul G. Ambrose, Sujata M. Bhavnani, Amber A. Beaudry, Kimberly Clawson Stone, Ian A. CritchleyAbstract: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,
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National and Regional Assessment of Antimicrobial Resistance among Community-Acquired Respiratory Tract Pathogens Identified in a 2005-2006 U.S. Faropenem Surveillance Study
Antimicrobial agents and chemotherapy, 2007Co-Authors: Ian A. Critchley, Glenn S. Tillotson, Steven D. Brown, Maria M. Traczewski, Nebojsa JanjicAbstract:Surveillance studies conducted in the United States over the last decade have revealed increasing resistance among community-acquired respiratory pathogens, especially Streptococcus pneumoniae, that may limit future options for empirical therapy. The objective of this study was to assess the scope and magnitude of the problem at the national and regional levels during the 2005-2006 respiratory season (the season when community-acquired respiratory pathogens are prevalent) in the United States. Also, since Faropenem is an oral penem being developed for the treatment of community-acquired respiratory tract infections, another study objective was to provide baseline data to benchmark changes in the susceptibility of U.S. respiratory pathogens to the drug in the future. The in vitro activities of Faropenem and other agents were determined against 1,543 S. pneumoniae isolates, 978 Haemophilus influenzae isolates, and 489 Moraxella catarrhalis isolates collected from 104 U.S. laboratories across six geographic regions during the 2005-2006 respiratory season. Among S. pneumoniae isolates, the rates of resistance to penicillin, amoxicillin-clavulanate, and cefdinir were 16, 6.4, and 19.2%, respectively. The least effective agents were trimethoprim-sulfamethoxazole (SXT) and azithromycin, with resistance rates of 23.5 and 34%, respectively. Penicillin resistance rates for S. pneumoniae varied by region (from 8.7 to 22.5%), as did multidrug resistance rates for S. pneumoniae (from 8.8 to 24.9%). Resistance to beta-lactams, azithromycin, and SXT was higher among S. pneumoniae isolates from children than those from adults. beta-Lactamase production rates among H. influenzae and M. catarrhalis isolates were 27.4 and 91.6%, respectively. Faropenem MICs at which 90% of isolates are inhibited were 0.5 mug/ml for S. pneumoniae, 1 mug/ml for H. influenzae, and 0.5 mug/ml for M. catarrhalis, suggesting that Faropenem shows promise as a treatment option for respiratory infections caused by contemporary resistant phenotypes.
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Activity of Faropenem against Middle Ear Fluid Pathogens from Children with Acute Otitis Media in Costa Rica and Israel
Antimicrobial agents and chemotherapy, 2007Co-Authors: Kimberley Clawson Stone, Roger Echols, Ron Dagan, Adriano Arguedas, Eugene Leibovitz, Elaine Wang, Nebojsa Janjic, Ian A. CritchleyAbstract:Faropenem was tested against 1,188 middle ear fluid pathogens from children in Israel and Costa Rica. Against Streptococcus pneumoniae and Haemophilus influenzae, Faropenem was the most active β-lactam, with activity that was similar to or greater than of the other oral antimicrobial classes studied. Faropenem was also active against Moraxella catarrhalis and Streptococcus pyogenes.
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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National and Regional Assessment of Antimicrobial Resistance among Community-Acquired Respiratory Tract Pathogens Identified in a 2005-2006 U.S. Faropenem Surveillance Study
Antimicrobial agents and chemotherapy, 2007Co-Authors: Ian A. Critchley, Glenn S. Tillotson, Steven D. Brown, Maria M. Traczewski, Nebojsa JanjicAbstract:Surveillance studies conducted in the United States over the last decade have revealed increasing resistance among community-acquired respiratory pathogens, especially Streptococcus pneumoniae, that may limit future options for empirical therapy. The objective of this study was to assess the scope and magnitude of the problem at the national and regional levels during the 2005-2006 respiratory season (the season when community-acquired respiratory pathogens are prevalent) in the United States. Also, since Faropenem is an oral penem being developed for the treatment of community-acquired respiratory tract infections, another study objective was to provide baseline data to benchmark changes in the susceptibility of U.S. respiratory pathogens to the drug in the future. The in vitro activities of Faropenem and other agents were determined against 1,543 S. pneumoniae isolates, 978 Haemophilus influenzae isolates, and 489 Moraxella catarrhalis isolates collected from 104 U.S. laboratories across six geographic regions during the 2005-2006 respiratory season. Among S. pneumoniae isolates, the rates of resistance to penicillin, amoxicillin-clavulanate, and cefdinir were 16, 6.4, and 19.2%, respectively. The least effective agents were trimethoprim-sulfamethoxazole (SXT) and azithromycin, with resistance rates of 23.5 and 34%, respectively. Penicillin resistance rates for S. pneumoniae varied by region (from 8.7 to 22.5%), as did multidrug resistance rates for S. pneumoniae (from 8.8 to 24.9%). Resistance to beta-lactams, azithromycin, and SXT was higher among S. pneumoniae isolates from children than those from adults. beta-Lactamase production rates among H. influenzae and M. catarrhalis isolates were 27.4 and 91.6%, respectively. Faropenem MICs at which 90% of isolates are inhibited were 0.5 mug/ml for S. pneumoniae, 1 mug/ml for H. influenzae, and 0.5 mug/ml for M. catarrhalis, suggesting that Faropenem shows promise as a treatment option for respiratory infections caused by contemporary resistant phenotypes.
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Activity of Faropenem against Middle Ear Fluid Pathogens from Children with Acute Otitis Media in Costa Rica and Israel
Antimicrobial agents and chemotherapy, 2007Co-Authors: Kimberley Clawson Stone, Roger Echols, Ron Dagan, Adriano Arguedas, Eugene Leibovitz, Elaine Wang, Nebojsa Janjic, Ian A. CritchleyAbstract:Faropenem was tested against 1,188 middle ear fluid pathogens from children in Israel and Costa Rica. Against Streptococcus pneumoniae and Haemophilus influenzae, Faropenem was the most active β-lactam, with activity that was similar to or greater than of the other oral antimicrobial classes studied. Faropenem was also active against Moraxella catarrhalis and Streptococcus pyogenes.
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Activity of Faropenem tested against Neisseria gonorrhoeae isolates including fluoroquinolone-resistant strains.
Diagnostic microbiology and infectious disease, 2005Co-Authors: Ronald N. Jones, Nebojsa Janjic, Ian A. Critchley, William L.h. Whittington, Sudha PottumarthyAbstract:Abstract We evaluated the anti-gonococcal potency of Faropenem along with 7 comparator reference antimicrobials against a preselected collection of clinical isolates. The 265 isolates were inclusive of 2 subsets: 1) 76 well-characterized resistant phenotypes of gonococcal strains (53 quinolone-resistant strains—31 with documented quinolone resistance-determining region changes from Japan, 15 strains resistant to penicillin and tetracycline, and 8 strains with intermediate susceptibility to penicillin) and 2) 189 recent isolates from clinical specimens in 2004 from 6 states across the United States where quinolone resistance is prevalent. Activity of Faropenem was adversely affected by l-cysteine hydrochloride in IsoVitaleX (4-fold increase in [minimal inhibitory concentration] MIC 50 ; 0.06 versus 0.25 μg/mL). The rank order of potency of the antimicrobials for the entire collection was ceftriaxone (MIC 90 , 0.06 μg/mL) > Faropenem (0.25 μg/mL) > azithromycin (0.5 μg/mL) > cefuroxime (1 μg/mL) > tetracycline (2 μg/mL) > penicillin=ciprofloxacin = levofloxacin (4 μg/mL). Using MIC 90 for comparison, Faropenem was 4-fold more potent than cefuroxime (0.25 versus 1 μg/mL), but was 4-fold less active than ceftriaxone (0.25 versus 0.06 μg/mL). Although the activity of Faropenem was not affected by either penicillinase production (MIC 90 , 0.12 μg/mL, penicillinase-positive) or increasing ciprofloxacin MIC (0.25 μg/mL, ciprofloxacin-resistant), increasing penicillin MIC was associated with an increase in MIC 90 values (0.016 μg/mL for penicillin-susceptible to 0.25 μg/mL for penicillin-resistant strains). Among the recent (2004) clinical gonococcal isolates tested, reduced susceptibility to penicillins, tetracycline, and fluoroquinolones was high (28.0–94.2%). Geographic distribution of the endemic resistance rates of gonococci varied considerably, with 16.7–66.7% of the gonococcal isolates being ciprofloxacin-resistant in Oregon, California, Washington, and Hawaii. Faropenem retained its potency against these recent clinical strains and also quinolone-resistant strains from Japan (MIC 90 , ≤0.25 μg/mL). In summary, the excellent activity of Faropenem against the gonococcal strains analyzed irrespective of the resistance phenotype, along with its β-lactamase stability, makes it an ideal contender for further development as an oral β-lactam agent to treat uncomplicated gonococcal infections due to strains emerging with resistant to penicillins, tetracyclines, and fluoroquinolones.
Peter C. Appelbaum - One of the best experts on this subject based on the ideXlab platform.
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Binding of Faropenem and Other β-Lactam Agents to Penicillin-Binding Proteins of Pneumococci with Various β-Lactam Susceptibilities
Antimicrobial agents and chemotherapy, 2009Co-Authors: Klaudia Kosowska-shick, Pamela Mcghee, Peter C. AppelbaumAbstract:Faropenem demonstrated low MICs (≤1 μg/ml) for all penicillin-susceptible and nonsusceptible pneumococci and exhibited very strong abilities to bind to Streptococcus pneumoniae penicillin-binding proteins (PBPs), except for PBP2X. The lower Faropenem affinity for PBP2X did not affect MICs for any strains tested, and only imipenem had lower MICs, with much lower binding affinities for all PBPs tested, than Faropenem.
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In Vitro Capability of Faropenem To Select for Resistant Mutants of Streptococcus pneumoniae and Haemophilus influenzae
Antimicrobial agents and chemotherapy, 2007Co-Authors: Klaudia Kosowska-shick, Catherine Clark, Kim L. Credito, Bonifacio Dewasse, Linda Beachel, Lois M. Ednie, Peter C. AppelbaumAbstract:When tested against nine strains of pneumococci and six of Haemophilus influenzae of various resistotypes, Faropenem failed to select for resistant mutants after 50 days of consecutive subculture in subinhibitory concentrations. Faropenem also yielded low rates of spontaneous mutations against all organisms of both species. By comparison, resistant clones were obtained with macrolides, ketolides, and quinolones.
Daniel F. Sahm - 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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Activities of Faropenem, an Oral β-Lactam, against Recent U.S. Isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis
Antimicrobial agents and chemotherapy, 2002Co-Authors: Ian A. Critchley, James A Karlowsky, Deborah C. Draghi, Mark E. Jones, Clyde Thornsberry, Kate Murfitt, Daniel F. SahmAbstract:The in vitro activities of Faropenem and other antimicrobial agents were determined against 4,725 Streptococcus pneumoniae isolates, 2,614 Haemophilus influenzae isolates, and 1,193 Moraxella catarrhalis isolates collected from 273 U.S. laboratories during 1999. Faropenem MICs at which 90% of isolates are inhibited were 0.008, 0.25, and 1 microg/ml for penicillin-susceptible, -intermediate, and -resistant S. pneumoniae strains, respectively; 0.5 and 1 microg/ml for beta-lactamase-positive and -negative H. influenzae strains, respectively; and 0.12 and 0.5 microg/ml for beta-lactamase-negative and -positive M. catarrhalis strains, respectively. Faropenem holds promise as an oral therapy for community-acquired respiratory tract infections.
Klaudia Kosowska-shick - One of the best experts on this subject based on the ideXlab platform.
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2016Co-Authors: Klaudia Kosowska-shick, Pamela McgheeAbstract:.org/ D ow nloaded from 2 Faropenem gave low MICs (≤1 µg/ml) against all penicillin susceptible and non-susceptible pneumococci and demonstrated very good binding abilities to Streptococcus pneumoniae penicillin-binding proteins (PBPs) except for PBP2X. Lower Faropenem affinity to PBP2X did not affect MICs value in any strains tested and only imipenem had lower MICs with much lower binding affinity to all PBPs tested compared to Faropenem. o
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Binding of Faropenem and Other β-Lactam Agents to Penicillin-Binding Proteins of Pneumococci with Various β-Lactam Susceptibilities
Antimicrobial agents and chemotherapy, 2009Co-Authors: Klaudia Kosowska-shick, Pamela Mcghee, Peter C. AppelbaumAbstract:Faropenem demonstrated low MICs (≤1 μg/ml) for all penicillin-susceptible and nonsusceptible pneumococci and exhibited very strong abilities to bind to Streptococcus pneumoniae penicillin-binding proteins (PBPs), except for PBP2X. The lower Faropenem affinity for PBP2X did not affect MICs for any strains tested, and only imipenem had lower MICs, with much lower binding affinities for all PBPs tested, than Faropenem.
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In Vitro Capability of Faropenem To Select for Resistant Mutants of Streptococcus pneumoniae and Haemophilus influenzae
Antimicrobial agents and chemotherapy, 2007Co-Authors: Klaudia Kosowska-shick, Catherine Clark, Kim L. Credito, Bonifacio Dewasse, Linda Beachel, Lois M. Ednie, Peter C. AppelbaumAbstract:When tested against nine strains of pneumococci and six of Haemophilus influenzae of various resistotypes, Faropenem failed to select for resistant mutants after 50 days of consecutive subculture in subinhibitory concentrations. Faropenem also yielded low rates of spontaneous mutations against all organisms of both species. By comparison, resistant clones were obtained with macrolides, ketolides, and quinolones.
