Abstract:
:An in vitro pharmacodynamic model was used to simulate the in vivo pharmacokinetics of clarithromycin and 14-hydroxyclarithromycin in order to generate time-kill curves for three clinical isolates of Haemophilus influenzae (isolates 2019, 91-183, and 1746). Representative concentrations in serum or lung tissue and the pharmacokinetic parameters of clarithromycin and the 14-hydroxy metabolite, separately and in combination, were simulated for the time-kill studies. Amoxicillin-clavulanic acid was used as a control drug. The simulation of typical concentrations of the macrolides in serum in time-kill studies resulted in magnitudes of bacterial killing that were less than (for strains 2019 and 91-183, MICs = 4 mg/liter for clarithromycin and 14-hydroxy-clarithromycin) or equal to (for strain 1746, MIC = 1 mg/liter for clarithromycin and 14-hydroxyclarithromycin) those observed in amoxicillin-clavulanic acid studies. When typical concentrations in lung tissue were simulated, total log decreases in bacterial counts were greater than those achieved with typical concentrations in serum and, in the case of strain 1746, exceeded the magnitude observed with the control drug. In each case, the time to 3-log-unit killing was longer for the macrolides than for amoxicillin-clavulanic acid. Time-kill curve analyses demonstrated the presence of synergy (defined as a 2-log-unit decrease in the CFU per milliliter between the combination and the most active constituent at any time point) for the combination of clarithromycin and 14-hydroxyclarithromycin at simulated concentrations in serum for one strain of H. influenzae (isolate 91-183). Synergism is likely bacterial strain specific, and the presence of synergy may be dependent on the antibiotic concentrations that are tested. Evaluation of the kill curve kinetics in terms of bactericidal rate for the various starting concentrations of clarithromycin did not result in a clear demonstration of either concentration-dependent or concentration-independent bactericidal activity.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Walker KJ,Larsson AJ,Zabinski RA,Rotschafer JCdoi
10.1128/aac.38.9.2003subject
Has Abstractpub_date
1994-09-01 00:00:00pages
2003-7issue
9eissn
0066-4804issn
1098-6596journal_volume
38pub_type
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.34.11.2277
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
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更新日期:2011-12-01 00:00:00
abstract::A novel beta-lactamase gene, blaOXA-61, from Campylobacter jejuni GC015 was cloned and its nucleotide sequence determined. blaOXA-61 encodes a protein of 257 amino acids in which the active-site STFK tetrad and conserved class D beta-lactamase motifs YGN and KTG were identified. A conserved sequence upstream of blaOXA...
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.7.982
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pub_type: 杂志文章
doi:10.1128/AAC.02223-16
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
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pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01216-06
更新日期:2007-04-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:2005-11-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
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更新日期:2005-10-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:2014-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:1982-05-01 00:00:00