Low prevalence of Gram-positive isolates showing elevated lefamulin MIC results during the surveillance program for 2015-2016 and characterization of resistance mechanisms [Mechanisms of Resistance]

This study investigated the molecular mechanisms possibly associated with non-wildtype MICs for lefamulin among staphylococci and streptococci included in the lefamulin surveillance program for 2015-2016. A total of 2,919 Staphylococcus aureus, 276 coagulase-negative staphylococci (CoNS), 3,923 Streptococcus pneumoniae, 389 ß-hemolytic and 178 viridans group streptococci were included in the surveillance studies. Eleven (0.3% of all S. aureus) S. aureus with lefamulin MICs above the staphylococcal epidemiological cut-off (ECOFF) value (>0.25 μg/mL) were selected for this study. Eight (72.7%) S. aureus (lefamulin MIC, 0.5-4 μg/mL) carried vga(A or E), one isolate (MIC, 32 μg/mL) carried lsa(E), one isolate (MIC, 16 μg/mL) had an alteration in L4, and one strain (MIC, 0.5 μg/mL) did not carry any of the investigated resistance mechanisms. A total of 14 (5.1% of all CoNS) CoNS had lefamulin MICs (0.5 to >32 μg/mL) above ECOFF. Similar to S. aureus, 8 (57.1%) CoNS (lefamulin MIC, 1-8 μg/mL) carried vga(A or B), while 2 isolates (MIC, 4-32 μg/mL) carried cfr. High genetic diversity was observed among staphylococci, although 3 S. aureus belonged to ST398. Among 3 S. agalactiae and 3 viridans group streptococci (0.1% of all streptococci surveyed) selected for additional characterization, and all but 1 isolate carried lsa(E). This study documents a low occurrence of surveillance isolates exhibiting a non-wildtype MIC for lefamulin, and among these isolates, vga and lsa(E) prevailed in staphylococci and streptococci, respectively.

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