ANTIMICROBIAL ACTIVITY OF DALBAVANCIN AGAINST GRAM-POSITIVE BACTERIA ISOLATED FROM PATIENTS WITH INFECTIVE ENDOCARDITIS FROM THE UNITED STATES AND EUROPE (2016-2020): RESULTS FROM THE INTERNATIONAL DALBAVANCIN EVALUATION OF ACTIVITY (IDEA) PROGRAM

Abstract

TOPIC: Chest Infections TYPE: Original Investigations PURPOSE: The management of infective endocarditis (IE) requires aggressive and prolonged antimicrobial treatment. Dalbavancin (DALBA) has demonstrated potent in vitro activity against gram-positive (GP) organisms commonly responsible for IE and is being evaluated for treatment of complicated bacteremia and IE. METHODS: 16,164 GP organisms were consecutively collected from patients with bloodstream infections (BSIs) in the United States (US; 8,807 isolates from 79 hospitals) and Europe (EU; 7,357 isolates from 42 hospitals in 20 countries) from 2016 to 2020 via the IDEA Program. The collection included 323 isolates from patients with a diagnosis of IE. Isolates were tested for susceptibility (S) against DALBA and comparators by the CLSI broth microdilution method. RESULTS: Among IE isolates, the most common organisms were S. aureus (SA; 52.3%), E. faecalis (EF; 18.0%), and viridans group streptococci (VGS; 10.8%). Among BSI isolates, the most common organisms were SA (45.0%), β-hemolytic streptococci (BHS; 11.0%), and EF (10.8%). DALBA and daptomycin (DAPTO) showed complete activity (100.0%S) against SA from IE, but MIC values from DALBA (MIC50/90, 0.03/0.03 mg/L) were 8- to 16-fold lower than DAPTO (MIC50/90, 0.25/0.5 mg/L). Against SA from IE, linezolid (LZD) and teicoplanin (TEI) were active against 100.0% of isolates and ceftaroline was active against 99.0% of isolates. Vancomycin (VAN) inhibited 98.8% of isolates at ≤1 mg/L. Methicillin-resistant SA (MRSA) rates were 43.3% (US) and 27.5% (EU) among SA from IE (n=169), and 41.1% (US) and 24.0% (EU) among SA from BSI (n=7,279). All EF isolates from IE were S to ampicillin and LZD, whereas 98.3% were S to DALBA (MIC50/90, 0.03/0.06 mg/L), DAPTO (MIC50/90, 0.5/1 mg/L), VAN (MIC50/90, 1/2 mg/L), and TEI (MIC50/90, ≤0.5/≤0.5 mg/L). Against EF, DALBA MIC values were 16- to 32-fold lower than DAPTO and VAN. Among EF from BSI (n=1,748), S to DALBA, DAPTO, and VAN was 98.0%, 99.5%, and 97.7%, respectively. All VGS isolates from IE (n=35) were S to DALBA (at ≤0.12 mg/L), VAN, and LZD; 96.6% of VGS were S to DAPTO. All coagulase-negative staphylococci from IE were S to DALBA (MIC50/90, 0.03/0.12 mg/L; highest MIC, 0.12 mg/L), DAPTO (MIC50/90, 0.25/0.5 mg/L), VAN (MIC50/90, 2/2 mg/L), and LZD (MIC50/90, 1/1 mg/L). E. faecium (EFM) was isolated from 5.6% of IE cases. Among EFM isolates from IE, 66.7% were S to VAN and 72.2% were inhibited at ≤0.12 mg/L of DALBA. BHS was S to DALBA (highest MIC, 0.03 mg/L) and most antimicrobial agents tested. CONCLUSIONS: DALBA exhibited potent in vitro activity against a large collection of contemporary GP isolates recovered from patients with BSI, including IE, in US and EU medical centers. CLINICAL IMPLICATIONS: Due to its prolonged half-life and high potency against GP, DALBA may represent a valuable option for treatment of IE. These results support further investigations on the role of DALBA in the treatment of BSI and IE. DISCLOSURES: my employer received research support relationship with AbbVie Please note: 2020-2022 Added 04/20/2021 by Cecilia Carvalhaes, source=Web Response, value=Grant/Research Support No relevant relationships by Mariana Castanheira, source=Web Response no disclosure on file for Rodrigo Mendes;Research Contractor relationship with Allergan Please note: $1001 - $5000 by Helio Sader, source=Web Response, value=Grant/Research Support Research Contractor relationship with AbbVIe (formerly Allergan) Please note: Ongoing Added 04/15/2021 by Helio Sader, source=Web Response, value=Grant/Research Support No relevant relationships by Streit Streit, source=Web Response