Susceptibilities of healthcare- and community-associated methicillin-resistant staphylococci to the novel des-F(6)-quinolone DX-619.
OBJECTIVE
The aim of the study was to test in vitro activities of the novel des-F(6)-quinolone DX-619 against methicillin-resistant staphylococci (MRS) isolated in hospitals and communities and to compare its activity with other quinolones, sitafloxacin and levofloxacin, and antibiotics used for the treatment of methicillin-resistant Staphylococcus aureus infection, including vancomycin, teicoplanin, arbekacin, linezolid and quinupristin/dalfopristin.


METHODS
MICs were determined by the agar dilution method using healthcare-associated MRS (S. aureus including strains with reduced susceptibility to vancomycin, 103; coagulase-negative staphylococci, 87) and community-associated MRS (S. aureus including non-multiresistant oxacillin-resistant strains, 37; coagulase-negative staphylococci, 92). The quinolone resistance-determining regions of gyrA, gyrB, grlA and grlB genes from six strains with reduced susceptibility to DX-619 were sequenced.


RESULTS
DX-619 showed the lowest MIC(90) values for all categories of strains tested, irrespective of the degree of glycopeptide resistance. The six strains with MIC values of >128 mg/L of levofloxacin commonly carried two mutations in gyrA and two mutations in grlA. DX-619 showed potent activity against strains with MIC values of 2 mg/L.


CONCLUSIONS
DX-619 was potent against all MRS tested, suggesting that it would be a promising candidate for the treatment of methicillin-resistant S. aureus infection if sufficient in vivo concentrations were safely attained.
Watanabe
Shinya
S
Department of Infection Control Science, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan.
Ito
Teruyo
T
Hiramatsu
Keiichi
K
D000890:Anti-Infective Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003030:Coagulase / Q000378:metabolism; D017714:Community-Acquired Infections / Q000382:microbiology*; D003428:Cross Infection / Q000382:microbiology*; D027081:DNA Gyrase / Q000235:genetics / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D006801:Humans; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D011759:Pyrrolidines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology
D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D003030:Coagulase; C505440:DX 619; D011759:Pyrrolidines; D015363:Quinolones; D027081:DNA Gyrase