Activity of novel oxazolidinones against Nocardia brasiliensis growing within THP-1 macrophages

Abstract

Background: Nocardia are organisms that can escape the effects of both immune response and antimicrobial agents, due to their potential capacity to grow intracellularly. In previous studies, we found that experimental oxazolidinones, DA-7157 and DA-7218, are active both in vitro and in vivo. Objectives: In this study, we compare the ability of linezolid, DA-7157 and DA-7218 to inhibit intracellular growth of Nocardia brasiliensis within the human monocyte cell line THP-1. Methods and results: The addition of oxazolidinones to the infected macrophage monolayer at concentrations 0.25×, 1×, 4× and 16× the MIC for N. brasiliensis resulted in an inhibitory effect on bacterial growth as follows DA-7157 ≥ DA-7218 > linezolid. Conclusions: The xcellent intracellular antimicrobial activity detected suggests that these compounds could be effective in the treatment of actinomycetoma. However, more studies are needed both in vitro and in vivo, including clinical trials, to confirm this issue. © The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.