Targeting Dalbavancin Inoculum Effect: Adjunctive Single Dose of Daptomycin

Autor: Razieh Kebriaei, Jacinda C. Abdul-Mutakabbir, Kyle C. Stamper, Katherine L. Lev, Michael J. Rybak
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Infectious Diseases and Therapy, Vol 12, Iss 10, Pp 2485-2494 (2023)
Druh dokumentu: article
ISSN: 2193-8229
2193-6382
00743046
DOI: 10.1007/s40121-023-00875-1
Popis: Abstract Introduction Daptomycin (DAP) has proven to be a viable alternative amid vancomycin resistance; however, the use of DAP post vancomycin treatment has led to the development of DAP non-susceptible (DNS) strains. Dalbavancin (DAL), a novel single-dosed lipoglycopeptide, has shown enhanced activity against highly resistant Staphylococcus aureus strains. However, on the basis of previous reports and our observations, DAL does not demonstrate similar activity at high versus low inoculum levels. Therefore, we hypothesized that addition of DAP even at minimal concentrations (single dose on day 1) will lower the inoculum to the level that can be cleared by dalbavancin. Methods Isolates from methicillin-resistant S. aureus (MRSA)-infected patients with varying susceptibility profiles were evaluated using broth microdilution methods. Two DNS–VISA strains (vancomycin intermediate resistant S. aureus) and one MRSA strain were further evaluated in a one-compartment PK/PD model using a high starting initial inoculum of 109 CFU/mL as well as low initial inoculum of 107 CFU/mL over 168 h to assess the activity of DAL and DAP monotherapy and in combination. Results Single therapies were not bactericidal when evaluated in the 168 h in vitro one-compartment model with an initial inoculum of 109; however, the combination of DAL plus single dose of DAP resulted in enhanced killing at the end of the 168-h exposure. DAL single therapy caused reduction in colony counts down to detection limit (2 log10 CFU/ml) at a lower inoculum but did not show enhancement (
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