In vitro and in vivo antibacterial evaluation of DRF 8417, a new oxazolidinone.
OBJECTIVE
DRF 8417, a novel oxazolidinone, has been evaluated against Gram-positive and fastidious Gram-negative bacteria. In vitro activity of DRF 8417 was determined by broth microdilution method and in vivo efficacy studies were carried out in different murine systemic infection models.


RESULTS
DRF 8417 exhibited potent activity against Gram-positive pathogens with MIC(50) and MIC(90) values ranging from 0.06 to 1 mg/L. MICs against Haemophilus influenzae and Moraxella catarrhalis were one to two dilutions lower than those of linezolid. The in vivo efficacy, by oral route, in different susceptible and resistant Gram-positive systemic bacterial infection models ranged from 2.0 to 2.9 mg/kg.


CONCLUSIONS
These studies displayed the excellent in vitro and in vivo activity of DRF 8417 against Gram-positive pathogens and lower MICs when compared with linezolid against H. influenzae and M. catarrhalis.
Sreenivas
K
K
Anti-infective Group, Discovery Research, Dr Reddy's Laboratories Ltd, Miyapur, Hyderabad 500 049, India. sreenivaskandepu@drreddys.com
Amarnath
P V S
PV
Mallik
A
A
Sarnaik
H
H
Kumar
N Selva
NS
Takhi
M
M
Trehan
S
S
Kumar
M Sitaram
MS
Iqbal
J
J
Rajagopalan
R
R
Chakrabarti
R
R
D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006095:Gram-Positive Cocci / Q000187:drug effects*; D006192:Haemophilus Infections / Q000188:drug therapy / Q000382:microbiology; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis / Q000187:drug effects*; D045828:Moraxellaceae Infections / Q000188:drug therapy / Q000382:microbiology; D023303:Oxazolidinones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013047:Specific Pathogen-Free Organisms; D016896:Treatment Outcome; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000378:metabolism
D000890:Anti-Infective Agents; D023303:Oxazolidinones; D001618:beta-Lactamases