Abstract:
:To describe the relationship between the ratio of the 24-h area under the concentration-time curve (AUC(24)) to minimum inhibitory concentration (MIC) as well as the effect of linezolid on Staphylococcus aureus, the killing kinetics of three S. aureus strains was studied by in vitro simulation of 5-day antibiotic dosing over a wide range of AUC(24)/MIC ratios. Similarly susceptible meticillin-resistant S. aureus ATCC 43300 and S. aureus 479 and vancomycin-intermediate S. aureus ATCC 700699 (Mu50) at a starting inoculum of 10(8) colony-forming units (CFU)/mL were exposed to multiple-dose pharmacokinetics of twice-daily linezolid for 5 days. The simulated AUC(24)/MIC ratios varied from 30 h to 1200 h (S. aureus ATCC 43300), from 30h to 600 h (S. aureus 479) and from 50h to 400 h (S. aureus ATCC 700699). The cumulative antimicrobial effect was expressed by its intensity (I(E)) measured from the start of treatment to the time after the last antibiotic dose when numbers of antibiotic-exposed bacteria reached >or=10(8)CFU/mL. With each organism, bacterial re-growth followed a pronounced reduction of the starting inoculum that occurred at each simulated AUC(24)/MIC ratio except for the lowest value (30 h). This reduction was AUC(24)/MIC-dependent: the minimum numbers of surviving organisms decreased with increasing AUC(24)/MIC ratios. A sigmoid relationship was established between I(E) and the simulated AUC(24)/MIC ratio. This relationship was bacterial strain-independent; a logistic function fits the combined data with r(2)=0.95. The established AUC(24)/MIC-I(E) relationship is useful to predict the antistaphylococcal effects of linezolid at clinically attainable AUC(24)/MIC values.
journal_name
Int J Antimicrob Agentsjournal_title
International journal of antimicrobial agentsauthors
Strukova EN,Smirnova MV,Vostrov SN,Lubenko IY,Firsov AA,Zinner SH,Portnoy YAdoi
10.1016/j.ijantimicag.2008.09.006subject
Has Abstractpub_date
2009-03-01 00:00:00pages
251-4issue
3eissn
0924-8579issn
1872-7913pii
S0924-8579(08)00451-2journal_volume
33pub_type
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journal_title:International journal of antimicrobial agents
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journal_title:International journal of antimicrobial agents
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journal_title:International journal of antimicrobial agents
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journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
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journal_title:International journal of antimicrobial agents
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journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
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journal_title:International journal of antimicrobial agents
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