Evaluation of the Combined Therapy of DA-7218, a New Oxazolidinone, and Trimethoprim/ Sulfamethoxazole in the Treatment of Experimental Actinomycetoma by Nocardia brasiliensis.

Abstract

OBJECTIVES:

Currently, for actinomycetoma, combined antimicrobial therapy is preferred to the use of a single compound. This is in order to provide a broader-spectrum coverage due to a combinatory or synergistic effect between the drugs, and to decrease the possibility of emergence of natural resistant strains. A new oxazolidinone pro-drug, DA-7218 [(R)-3-(4-(2-(2-methyltetrazol-5-yl)-pyridin-5-yl)-3-fluorophenyl)-2-oxo-5-oxazolidinyl) methyl-disodium-phosphate] (recently re-named TR-701), has shown very good in vitro and in vivo activities against several gram-positive bacteria including Nocardia spp.

METHODS:

In the present work we evaluated the effect of DA-7218 at two different doses, alone and combined with trimethoprim/ sulfamethoxazole (SXT), in an experimental Nocardia brasiliensis actinomycetoma murine model. We also included a negative and a positive control group (linezolid and saline solution respectively).

RESULTS:

At the end of the treatment period, we observed a clinically and statistically significant difference among the drug receiving groups (combined, alone and linezolid) and the control group (P=0.004). The difference was higher (P= 0.004) between the groups receiving DA-7218 (25mg/kg) alone or combined with SXT, and the control group (saline solution).

CONCLUSIONS:

In this work we proved that DA-7218 alone and combined with SXT is effective in the treatment of experimental actinomycetoma by Nocardia brasiliensis and that it could be potentially useful in the treatment of human actinomycetoma.

• Authors: N A Espinoza-Gonzalez, O Welsh, J Ocampo-Candiani, S Said-Fernandez, G Lozano-Garza, S H Choi, L Vera-Cabrera
• Journal: Current drug delivery (Curr Drug Deliv) Vol. 7 Issue 3 Pg. 225-9 (Jul 2010) ISSN: 1875-5704 [Electronic] United Arab Emirates
• PMID: 20497102 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Organophosphates
• Oxazoles
• Trimethoprim, Sulfamethoxazole Drug Combination
• tedizolid phosphate

Topics

• Animals
• Anti-Bacterial Agents (pharmacology)
• Bacterial Load
• Disease Models, Animal
• Drug Therapy, Combination
• Female
• Mice, Inbred BALB C
• Nocardia (drug effects, pathogenicity)
• Nocardia Infections (drug therapy, microbiology)
• Organophosphates (pharmacology)
• Oxazoles (pharmacology)
• Trimethoprim, Sulfamethoxazole Drug Combination (pharmacology)