In vitro activity of linezolid against clinically important gram-positive cocci in the United States: A 5-year summary of in vitro activity and resistance mechanisms from the LEADER Surveillance Program (2011--2015) [PublishAheadOfPrint]

This study describes linezolid susceptibility testing results for 6,741 gram-positive pathogens from 60 U.S. sites collected during 2015 for the LEADER Program. In addition, the study summarizes linezolid in vitro activity, resistance mechanisms, and molecular typing obtained for 2011 to 2015. During 2015, linezolid showed potent activity when tested against Staphylococcus aureus, inhibiting >99.9% of 3,031 isolates at ≤2 mg/liter. Similarly, linezolid showed coverage against 99.2% of coagulase-negative staphylococci, 99.7% of enterococci, and for 100.0% of Streptococcus pneumoniae, virdans group, and β-hemolytic streptococci tested. The overall linezolid resistance rate remained a modest <1% from 2011 to 2015. Staphylococci, specially Staphylococcus epidermidis, showed a range of linezolid resistance mechanisms. Increased annual trends for the presence of cfr among Staphylococcus aureus isolates were not observed, but 64.3% (9/14) of the isolates with decreased susceptibility (MIC, ≥4 mg/L) to linezolid carried this transferrable gene (2011—2015). The cfr gene was detected in 21.9% (7/32) of linezolid-resistant staphylococci other than S. aureus from 2011 to 2015. The optrA gene was noted in half (2/4) of linezolid-nonsusceptible Enterococcus faecalis from 2011 to 2015, while linezolid-nonsusceptible Enterococcus faecium showed alterations predominantly (16/16) in the 23S rRNA (G2576T). This report confirms a long record for the linezolid activity against gram-positive isolates in the United States since regulatory approval in 2000 and reposts the oxazolidinones evolving resistance mechanisms.

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