In vitro activity of the new quinolone WCK 771 against staphylococci.
The activity of WCK 771, an experimental quinolone developed to overcome quinolone resistance in staphylococci and other bacteria, was determined against quinolone-susceptible and -resistant Staphylococcus aureus and S. epidermidis. WCK 771 MICs for 50 and 90% of the strains tested (MIC(50) and MIC(90), respectively) were 0.008 and 0.015 microg/ml for S. aureus (n = 43) and 0.015 and 0.03 microg/ml for S. epidermidis (n = 44) for quinolone-susceptible isolates, compared to ciprofloxacin values of 0.12 and 0.25 microg/ml and 0.25 and 0.5 microg/ml, respectively. Values for levofloxacin were 0.12 and 0.25 microg/ml and 0.12 and 0.25 microg/ml, those for clinafloxacin were 0.015 and 0.03 microg/ml and 0.015 and 0.03 microg/ml, those for moxifloxacin were 0.03 and 0.06 microg/ml and 0.06 and 0.12 microg/ml, and those for gatifloxacin were 0.06 and 0.12 microg/ml and 0.12 and 0.25 microg/ml, respectively. The WCK 771 MIC(50) and MIC(90), respectively, were 0.5 and 1 microg/ml for both species of staphylococci (n = 73 for S. aureus, n = 70 for S. epidermidis) for isolates highly resistant to ciprofloxacin (MIC(50) and MIC(90), >32 and >32 microg/ml, respectively). Values for levofloxacin were 8 and 32 microg/ml and 8 and 32 microg/ml, those for clinafloxacin were 1 and 2 microg/ml and 0.5 and 2 microg/ml, those for moxifloxacin 4 and >4 microg/ml and 4 and >4 microg/ml, and those for gatifloxacin were 4 and >4 microg/ml and 2 and >4 microg/ml, respectively. WCK 771 and clinafloxacin demonstrated MICs of 1 microg/ml against three vancomycin-intermediate strains. WCK 771 showed concentration-independent killing for up to 24 h at 2, 4, and 8 times the MICs against quinolone-resistant staphylococci and was also bactericidal after 8 h for high-density inocula (10(8) CFU/ml) of quinolone-resistant strains at 5 microg/ml, whereas moxifloxacin at 7.5 microg/ml was bacteriostatic. WCK 771 was not a substrate of the NorA efflux pump as evident from the similar MICs against both an efflux-positive and an efflux-negative strain. Overall, WCK 771 was the most potent quinolone tested against the staphylococci tested, regardless of quinolone susceptibility.
Jacobs
Michael R
MR
Department of Pathology, Case Western Reserve University, Cleveland, OH, USA. mrj6@po.cwru.edu
Bajaksouzian
Saralee
S
Windau
Anne
A
Appelbaum
Peter C
PC
Patel
Mahesh V
MV
Gupte
Shrikant V
SV
Bhagwat
Sachin S
SS
De Souza
Noel J
NJ
Khorakiwala
Habil F
HF
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D015169:Colony Count, Microbial; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015363:Quinolones / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000382:microbiology; D013210:Staphylococcus / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D024841:Fluoroquinolones; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015363:Quinolones; C490933:WCK 771; C075040:NorA protein, Staphylococcus