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 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 ((I) over tilde (E)) increased with increasing simulated AUC24/MIC ratios. Each of the combined treatments produced greater (I) over tilde (E)s than the sum of linezolid and doxycycline (I) over tilde (E)s observed in the respective single drug treatments. This study suggests that linezolid combinations with doxycycline may be synergistic in treating staphylococcal infections.