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Antimicrobial Agents and Chemotherapy, September 2004, p. 3338-3342, Vol. 48, No. 9
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.9.3338-3342.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

In Vitro Activity of the New Quinolone WCK 771 against Staphylococci

Department of Pathology, Case Western Reserve University, Cleveland, Ohio,¹ Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania,² Wockhardt Research Center, Aurangabad, India³

Received 18 March 2004/ Returned for modification 10 April 2004/ Accepted 19 May 2004

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 (MIC₅₀ and MIC₉₀, respectively) were 0.008 and 0.015 µg/ml for S. aureus (n = 43) and 0.015 and 0.03 µg/ml for S. epidermidis (n = 44) for quinolone-susceptible isolates, compared to ciprofloxacin values of 0.12 and 0.25 µg/ml and 0.25 and 0.5 µg/ml, respectively. Values for levofloxacin were 0.12 and 0.25 µg/ml and 0.12 and 0.25 µg/ml, those for clinafloxacin were 0.015 and 0.03 µg/ml and 0.015 and 0.03 µg/ml, those for moxifloxacin were 0.03 and 0.06 µg/ml and 0.06 and 0.12 µg/ml, and those for gatifloxacin were 0.06 and 0.12 µg/ml and 0.12 and 0.25 µg/ml, respectively. The WCK 771 MIC₅₀ and MIC₉₀, respectively, were 0.5 and 1 µg/ml for both species of staphylococci (n = 73 for S. aureus, n = 70 for S. epidermidis) for isolates highly resistant to ciprofloxacin (MIC₅₀ and MIC₉₀, >32 and >32 µg/ml, respectively). Values for levofloxacin were 8 and 32 µg/ml and 8 and 32 µg/ml, those for clinafloxacin were 1 and 2 µg/ml and 0.5 and 2 µg/ml, those for moxifloxacin 4 and >4 µg/ml and 4 and >4 µg/ml, and those for gatifloxacin were 4 and >4 µg/ml and 2 and >4 µg/ml, respectively. WCK 771 and clinafloxacin demonstrated MICs of 1 µg/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 (10⁸ CFU/ml) of quinolone-resistant strains at 5 µg/ml, whereas moxifloxacin at 7.5 µg/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.

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