IN VITRO AND IN VIVO EFFECTS OF COMBINATIONS OF CEFOTAXIME OR OTHER β-LACTAMS WITH ROLITETRACYCLINE ON METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS

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Combinations of cefotaxime (CTX) or other five β-lactams with rolitetracycline (RTC) were examined using the checkerboard method for their synergistic effects against 27 strains of methicillin-resistant Staphylococcus aureus (MRSA), and the combination of CTX andRTC was further evaluated for its synergistic effect in vitro and in vivo against 1 or 2 strains. Synergy occurred against 44% of the strains when RTC was combined with CTX, 22 to 30% with cefazolin, methicillin, and ceftizoxime, and 4 to 11% with latamoxef and cefmetazole. No antagonism was found with any combinations tested. Killing curve studies also showed that CTX/RTC was synergistic between 3 and 24 hours after the beginning of exposure, and the synergy was especially strong at 24 hours and potencies of combined bactericidal effect determined at 24 hours were in the following order: the 2 antibiotics given simultaneously, CTX given 2 hours before RTC, and CTX given 2 hours after RTC. In addition, the 2 drugs in combination synergistically inhibited (a) mortality in mice infected intraperitoneally with MRSA and (b) formation of subcutaneous abscess induced by MRSA in mice. The results of our study indicate that β-lactams, especially CTX, had synergistic effects in vitro when combined with RTC against MRSA and that the combination of CTX and RTC was also synergistic in vivo.