Evaluation of the Combined Therapy of DA-7218, a New Oxazolidinone, and Trimethoprim/ Sulfamethoxazole in the Treatment of Experimental Actinomycetoma by Nocardia brasiliensis.
OBJECTIVE
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.
Espinoza-Gonzalez
N A
NA
Welsh
O
O
Ocampo-Candiani
J
J
Said-Fernandez
S
S
Lozano-Garza
G
G
Choi
S H
SH
Vera-Cabrera
L
L
Servicio de Dermatologia, Hospital Universitario "Dr. Jose E. Gonzalez", Ave. Francisco I. Madero y Ave. Dr. Jose Eleuterio Gonzalez S/N, Colonia Mitras Centro, Monterrey, N.L. 64460 Mexico. luvera_99@yahoo.com.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D058491:Bacterial Load; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D008807:Mice, Inbred BALB C; D009615:Nocardia / Q000187:drug effects* / Q000472:pathogenicity; D009617:Nocardia Infections / Q000188:drug therapy* / Q000382:microbiology; D010755:Organophosphates / Q000494:pharmacology*; D010080:Oxazoles / Q000494:pharmacology*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D010755:Organophosphates; D010080:Oxazoles; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; C515040:tedizolid phosphate