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) Vol. 23; no. 3; pp. 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:	Journal Article
Language:	English
Published:	Firenze Taylor & Francis 01-06-2011 EIFT Taylor & Francis Ltd
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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1120-009X 1973-9478
DOI:	10.1179/joc.2011.23.3.140