Antimicrobial Activity of Dalbavancin Tested against Staphylococcus aureus with Decreased Susceptibility to Glycopeptides, Daptomycin, and/or Linezolid from United States (US) Medical Centers

BACKGROUND: Dalbavancin (DALBA) was approved by the US Food and Drug Administration (2014) and European Medicines Agency (2015) for treating acute bacterial skin and skin structure infections. Dalbavancin activity was assessed against a large collection of S. aureus clinical isolates with decreased susceptibility (S) to key antimicrobial agents used to treat severe S. aureus infections. METHODS: The organism collection included isolates with decreased S to vancomycin (VAN; MIC ≥2 μg/mL; n = 1,141), daptomycin (DAPTO; MIC ≥2 μg/mL [resistant (R) per CLSI and EUCAST]; n = 48), telavancin (TLV; MIC ≥0.12 μg/mL; n = 73), teicoplanin (TEICO; MIC ≥4 μg/mL [non-S (NS) per EUCAST]; n = 143), and/or linezolid (LNZ; MIC ≥8 μg/mL [R per CLSI and EUCAST]; n = 25). Isolates were selected among 59,903 US isolates tested in 2002–2016. S testing was performed by CLSI methods and MIC results were interpreted per CLSI and EUCAST criteria. RESULTS: Only 8 of 59,903 (0.01%) S. aureus isolates tested were categorized as DALBA-NS (MIC, >0.25 μg/mL). DALBA retained activity against 99.3% of isolates with VAN MICs of ≥2 μg/mL (Table), whereas DAPTO (MIC(50/90), 0.5/1 μg/mL) and LNZ (MIC(50/90), 1/2 μg/mL) were active against 96.8% and 99.6% of isolates, respectively. DALBA (Table) and VAN (MIC(50/90), 2/2 μg/mL) retained activity against 95.8% of DAPTO-NS S. aureus. When tested against TEICO-NS (EUCAST) isolates, S rates for DALBA, DAPTO, VAN, and LNZ were 95.1%, 95.8%, 97.9%, and 100.0%, respectively; and DALBA was 4- to 32-fold more potent than these comparator agents. All LNZ-R isolates (100.0%) were S to DALBA (MIC(50/90), 0.06/0.06 μg/mL), DAPTO (MIC(50/90), 0.5/0.5 μg/mL), and VAN (MIC(50/90), 1/2 μg/mL), but DALBA was 8- and 16- to 32-fold more potent than DAPTO and VAN, respectively. MRSA rates ranged from 71.2–96.0% among these R subsets. CONCLUSION: DALBA retained potent in vitro activity against S. aureus isolates, displaying decreased susceptibility to agents commonly used to treat serious infections and was consistently more potent than comparator agents. DISCLOSURES: H. S. Sader, Allergan: Research Contractor, Research grant; R. E. Mendes, Allergan: Research Contractor, Research grant; L. R. Duncan, Allergan: Research Contractor, Research grant; M. A. Pfaller, Allergan: Research Contractor, Research grant; R. K. Flamm, Allergan: Research Contractor, Research grant