Abstract
Background
The management of endocarditis requires aggressive and prolonged antimicrobial treatment. Dalbavancin (DALBA) has demonstrated potent in vitro activity against Gram-positive (GP) organisms commonly responsible for endocarditis and is being evaluated for treatment of complicated bacteremia and infective endocarditis.
Methods
A total of 626 GP organisms were collected from patients with a diagnosis of bacterial endocarditis in the United States (n = 222) and Europe (n = 404) from 2007 to 2017 via the SENTRY Antimicrobial Surveillance Program and were tested for susceptibility (S) against DALBA and comparators by CLSI broth microdilution.
Results
The most common organisms were S. aureus (48.4%), E. faecalis (EF; 19.6%), and viridans group streptococci (VGS; 12.5%). DALBA and daptomycin (DAPTO) showed complete activity (100.0%S) against S. aureus, but DALBA MICs were 4- to 8-fold lower (table). Linezolid (LZD) and teicoplanin were also active against all SA; whereas vancomycin (VAN) and trimethoprim–sulfamethoxazole were active against 99.7% of isolates. Ceftaroline (CPT) exhibited potent activity against methicillin-susceptible S. aureus (MSSA; MIC90, 0.25 mg/L; 100.0%S) and inhibited 78.4% of methicillin-resistant S. aureus (MRSA) isolates at ≤1 mg/L. All EF isolates were S to ampicillin, DAPTO, and LZD, whereas 97.6% (120/123) of isolates were S to DALBA (MIC90, 0.06 mg/L) and 96.7%S to VAN (MIC90, 2 mg/L). Against EF, DALBA MIC values were 16- to 32-fold lower than DAPTO and VAN. All VGS and coagulase-negative staphylococcal (CoNS) isolates were S to DALBA, DAPTO, VAN, and LZD, and the highest CPT MICs were 0.5 mg/L for VGS and 4 mg/L for CoNS (93.5% inhibited at ≤1 mg/L). Against E. faecium (EFM), 65.7% of isolates were inhibited at ≤0.25 mg/L of DALBA and 62.9% were VAN-S. All EFM were S to DAPTO and LNZ. β-Hemolytic streptococci (BHS) was S to most antimicrobial agents, and only 66.7% of S. pneumoniae (SPN) isolates were PEN-S at ≤0.06 mg/L.
Conclusion
DALBA exhibited potent in vitro activity against a large collection of GP isolates recovered from patients with endocarditis in the United States and Europe medical centers. These results support further investigations to determine the role of DALBA in the treatment of infective endocarditis.
Disclosures
H. S. Sader, Allergan: Research Contractor, Research support. R. E. Mendes, Allergan: Research Contractor, Research support. M. A. Pfaller, Allergan: Research Contractor, Research support. R. K. Flamm, Allergan: Research Contractor, Research support.
Potency and Bactericidal Activity of Iclaprim against Recent Clinical Gram-Positive Isolates