Background Meropenem (MER) plus linezolid (LZD) is a potential antibiotic combination for ICU patients especially if a polymicrobic infection is suspected. We tested for in vitro antagonism or synergy with MER plus LZD against oxacillin-resistant Staphylococcus aureus (ORSA).
Methods In vitro synergy testing of 10 PFGE unique clinical blood isolates of ORSA obtained in 2004 was performed by an Etest method and time-kill assay (TKA). MER and LZD Etest strips were applied to different sections of inoculated Mueller-Hinton agar plates. The plates were incubated for 1 h at room temperature. The strips were removed after the agar was marked at the MIC value on each strip. A new LZD strip was placed over the area of the MER strip, exactly matching the corresponding MIC values. The same procedure was performed with a new MER strip over the area of the LZD strip. After incubation for 24 h, the ellipses were read, and the summation fractional inhibitory concentration (SFIC) was calculated: synergy # 0.5; indifference >0.5 to # 4; antagonism > 4. TKAs at 0 and 24 h were performed for all isolates according to NCCLS guidelines. Synergy was determined as a $ 2 log10 decrease in colony count after 24 h by the combination compared to the most active antibiotic alone, and antagonism was defined as a $ 2 log10 increase in colony count after 24 h by the combination compared to the most active drug alone.
Results No antagonism between MER and LZD was detected with either in vitro testing method. Synergy was found for 2 isolates using the Etest method (SFIC of 0.11 and 0.13) and 4 using the TKA (22.0, 22.2, 22.3, and 22.4 log10 decrease in colony counts). Eight isolates were indifferent with the Etest method (SFIC 0.52-1.35) and 6 with the TKA (0.1 to 21.3). All isolates, which showed synergism with one method (Etest, TKA), were found to be indifferent with the other. No standardized method exists for in vitro synergy testing.
Conclusions There was no evidence of in vitro antagonism with MER plus LZD in our 10 ORSA isolates. The clinical benefit of in vitro synergy by MER plus LZD against any strain of ORSA remains unknown.
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