734. Trend Analysis of Oritavancin and Comparator Agents Activity against Enterococcus Causing Infections in US Medical Centers between 2017–2019 and 2022
Authors: Carvalhaes Cecilia G , Mendes Rodrigo E , Shortridge Dee , Castanheira Mariana 
Published: November 2023

Abstract

Background
A new formulation of oritavancin (ORI) to be infused over 1 hour for the treatment of skin and skin structure infections was approved in 2021 by the US FDA. The activity of ORI and its comparators against Enterococcus (ENT) and resistant (R) subsets from US medical centers was evaluated comparatively between 2022 and 2017–2019.

Methods
4,462 ENT, including 246/2,556 E. faecalis (EF) from 2022 and 2017–2019, respectively, 148/1,348 E. faecium (EFM), and 14/150 other ENT were collected (1/patient) from 34 US medical centers. Isolates were identified by MALDI-TOF MS and standard microbiology tests and susceptibility (S) tested by CLSI broth microdilution. CLSI clinical breakpoints (BPs) and VanA/VanB phenotypes were used. ORI BPs against vancomycin (VAN)-S EF were applied to all ENT.

Results
ORI activity against ENT from 2022 (MIC50/90, 0.015/0.03 mg/L) was similar to 2017–2019 (MIC50/90, 0.015/0.06 mg/L; Table). ORI inhibited 97.5%/98.9% of ENT from 2022/2017–2019 at ≤ 0.12 mg/L. VAN and linezolid (LZD) inhibited 97.2%/98.4% and 99.6%/99.6% of ENT from 2022/2017–2019, at the respective BPs. ORI, VAN, LZD and daptomycin (DAP) showed stable S rates ( &gt; 96%) against EF. ORI remained active against 57.1/53.1% of VAN-R EF. VanA rates in VAN-R EF from 2022 and 2017–2019 were 85.7%/93.8%. ORI inhibited the 3 VanB EF isolates at ≤ 0.03 mg/L. LZD and DAP remained active against VAN-R EF (100%). Similar activity was noted for ORI against EFM from 2022 (MIC50/90, 0.008/0.06 mg/L) and 2017–2019 (MIC50/90, 0.008/0.03 mg/L). The EFM S rate to VAN was 35.1% in 2017–2019 and 39.2% in 2022. The S rates to ORI (VAN-S EF BPs) and LZD remained stable ( &gt; 98%) as well as rates of DAP susceptible dose-dependent (SDD; 96.6% in 2022 and 99.5% in 2017–2019). The VanB phenotype increased from 7.8% in 2017–2019 to 20.0% in 2022. ORI inhibited all VanB and 98.5% of VanA EFM at ≤ 0.12 mg/L. LZD inhibited 98.6%/99.4% of VanA EFM isolates in 2022/2017–2022. The DAP SDD rate slightly decreased against VanA EFM (99.7% to 93.1%). ORI and comparators were active against other ENT.

Conclusion
ORI exhibited potent and stable activity against ENT clinical isolates, including VAN-R EFM in US. An increase in VanB EFM phenotype and a slight decrease in the DAP SDD rates in VAN-R EFM subsets were noted over time.

Disclosures
Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Entasis: Grant/Research Support|GSK: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Dee Shortridge, PhD, Melinta: Grant/Research Support|Shionogi: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support