The Antistaphylococcal Pharmacodynamics of Linezolid Alone and in Combination with Doxycycline in an In Vitro Dynamic Model

To delineate the possible advantages of linezolid/doxycycline combinations over either drug alone, the in vitro pharmacodynamics of linezolid, doxycycline and linezolid plus doxycycline were studied with Staphylococcus aureus. S. aureus ATCC 43300 and a clinical isolate S. aureus 479 were exposed to...

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Bibliographic Details
Published in:Journal of chemotherapy (Florence) 2011-06, Vol.23 (3), p.140-144
Main Authors: Smirnova, M.V., Strukova, E.N., Portnoy, Y.A., Dovzhenko, S.A., Kobrin, M.B., Zinner, S.H., Firsov, A.A.
Format: Article
Language:eng ; rus
Subjects:
Acetamides - pharmacokinetics
Acetamides - pharmacology
Anti-Bacterial Agents - pharmacology
Anti-Infective Agents - pharmacokinetics
Anti-Infective Agents - pharmacology
Area Under Curve
doxycycline
Doxycycline - pharmacokinetics
Doxycycline - pharmacology
Drug Interactions
Drug Therapy, Combination
In Vitro dynamic models
Linezolid
Microbial Sensitivity Tests - methods
Models, Biological
Oxazolidinones - pharmacokinetics
Oxazolidinones - pharmacology
pharmacodynamics
Staphylococcal Infections - drug therapy
Staphylococcal Infections - microbiology
Staphylococcus aureus - drug effects
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Summary:To delineate the possible advantages of linezolid/doxycycline combinations over either drug alone, the in vitro pharmacodynamics of linezolid, doxycycline and linezolid plus doxycycline were studied with Staphylococcus aureus. S. aureus ATCC 43300 and a clinical isolate S. aureus 479 were exposed to twice-daily linezolid and once-daily doxycycline, alone and in combination, for five consecutive days. Three dosing regimens were simulated with each drug alone: linezolid (AUC 24 /MIC 30, 60 and 200 h - L30, L60 and L200, respectively) and doxycycline (AUC 24 /MIC 90, 180 and 520 h - D90, D180 and D520, respectively) and in combination: linezolid plus doxycycline (L30+D90; L60+D180 and L200+D520). With both S. aureus ATCC 43300 and S. aureus 479 exposed to linezolid or doxycycline, the area between the line crossing each time-kill curve at the level of 10 8 CFU/mL and the respective time-kill curve (Ĩ E ) increased with increasing simulated AUC 24 /MIC ratios. Each of the combined treatments produced greater Ĩ E s than the sum of linezolid and doxycycline Ĩ E s observed in the respective single drug treatments. This study suggests that linezolid combinations with doxycycline may be synergistic in treating staphylococcal infections.
ISSN:1120-009X
1973-9478
DOI:10.1179/joc.2011.23.3.140