Abstract

Abstract Background Patients undergoing hematologic, oncologic, and/or transplant treatment are at risk for infections. Appropriate antimicrobial management is crucial for patients with suspected or confirmed bloodstream infections (BSI). We evaluated the in vitro activity of oritavancin (ORI) and comparators against Gram-positive (GP) isolates causing BSI in patients from hematology/oncology and transplant units (HTU) in US medical centers. Methods 1,217 isolates (1/patient) were consecutively collected from HTU patients in 33 US hospitals during 2010-2019. Isolates were identified by MALDI-TOF and/or standard microbiological testing methods, and susceptibility (S) tested by CLSI reference broth microdilution in a central laboratory. CLSI breakpoints were applied. Results Enterococcus spp. (overall, 36.1%; E. faecium [EFM], 20.2%; E. faecalis [EF], 14.3%) and S. aureus (SA, 35.7%; 36.4% methicillin-resistant [MRSA]) were the most common organism groups, followed by coagulase-negative Staphylococcus (CoNS; 11.8%; 76.4% MR), Viridans group streptococci (VHS; 9.6%), and beta-haemolytic streptococci (BHS; 3.5%). ORI inhibited 96.7%/98.9% of EFM/EF at ≤0.12mg/L (S breakpoint for vancomycin [VAN]-S EF). Ampicillin (100.0%S), linezolid (LZD; 100.0%S), daptomycin (DAP; 98.3%S), and VAN (97.1%S) were also active against EF. Only ORI (96.7%S) and LZD (100.0%S) remained active against EFM. A VRE phenotype and elevated daptomycin MIC (2-4 mg/L) were noted in 72.8% and 55.3% of EFM, with ORI inhibiting 95.5% and 95.6% of these isolates at ≤0.12mg/L, respectively. ORI displayed equivalent MIC50/90 (0.03/0.06 mg/L) values against MSSA (99.3%S) and MRSA (99.4%S). ORI inhibited 95.5% of MRCoNS at ≤0.12mg/L (SA breakpoint). VAN, DAP, and LZD remained active against MRSA and MRCoNS. ORI was also active against BHS (MIC50/90, 0.03/0.25 mg/L; 95.2%S) and VGS (MIC50/90, 0.015/0.25 mg/L; 96.6%S) as was VAN (100.0%), DAP (100.0%), and LZD (100.0%/99.1%S, respectively). Conclusion VRE EFM, MRCoNS, and MRSA rates were generally high in BSI GP isolates recovered from patients in HTU. ORI was highly active and inhibited > 95% of isolates at MIC of ≤ 0.12mg/L from this unique collection, including R subsets such as VAN-R EFM, EFM displaying elevated DAP MIC (2-4 mg/L), MRSA, and MRCoNS. Disclosures Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Dee Shortridge, PhD, AbbVie: Grant/Research Support|JMI Laboratory: Employee|Melinta: Grant/Research Support|Menarini: Grant/Research Support|Shionogi: Grant/Research Support Helio S. Sader, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Pfizer: Grant/Research Support Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Office for Assistant Secretary of Defense for Health Affairs: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support|Spero Therapeutics: Grant/Research Support.

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