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 g/ml for S. aureus (n ‫؍‬ 43) and 0.015 and 0.03 g/ml for S. epidermidis (n ‫؍‬ 44) for quinolone-susceptible isolates, compared to ciprofloxacin values of 0.12 and 0.25 g/ml and 0.25 and 0.5 g/ml, respectively. Values for levofloxacin were 0.12 and 0.25 g/ml and 0.12 and 0.25 g/ml, those for clinafloxacin were 0.015 and 0.03 g/ml and 0.015 and 0.03 g/ml, those for moxifloxacin were 0.03 and 0.06 g/ml and 0.06 and 0.12 g/ml, and those for gatifloxacin were 0.06 and 0.12 g/ml and 0.12 and 0.25 g/ml, respectively. The WCK 771 MIC 50 and MIC 90 , respectively, were 0.5 and 1 g/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 g/ml, respectively). Values for levofloxacin were 8 and 32 g/ml and 8 and 32 g/ml, those for clinafloxacin were 1 and 2 g/ml and 0.5 and 2 g/ml, those for moxifloxacin 4 and >4 g/ml and 4 and >4 g/ml, and those for gatifloxacin were 4 and >4 g/ml and 2 and >4 g/ml, respectively. WCK 771 and clinafloxacin demonstrated MICs of 1 g/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 g/ml, whereas moxifloxacin at 7.5 g/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.As the prevalence of multidrug-resistant strains of Staphylococcus aureus and coagulase-negative staphylococci has increased worldwide, there has been an attendant need for effective new agents. Strains of Staphylococcus species have showed increasing resistance to ␤-lactam compounds. As early as the 1970s, 70 to 85% of S. aureus isolates were penicillin resistant (4). Previously a problem of nosocomial transmission-methicillin-resistant S. aureus (MRSA) prevalence in hospitals was estimated by the Centers for Disease Control and Prevention to be approximately 50% in 1998-it is increasingly a problem in the community (4). Methicillin resistance is often accompanied by resistance to other antimicrobial agents, including quinolones. A Mexican study of 211 strains of S. aureus (30 methicillin resistant) and 998 strains of coagulase-negative staphylococci (533 methicillin resistant) showed only 10% ciprofloxacin susceptibility among S. aureus isolates and 43% susceptibility to ciprofloxacin in the coagu...

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There is an urgent medical need for novel antibacterial agents to treat hospital infections, specially those caused by multidrug-resistant Gram-positive pathogens. The need may also be fulfilled by either exploring antibacterial agents having new mechanism of action or expanding known classes of antibacterial drugs. The paper describes a new chemical entity, compound 21, derived from hitherto little known "floxacin". The choice of the entity was made from a series of synthesized prodrugs and salts of the active chiral benzoquinolizine carboxylic acid, S-(-)-nadifloxacin. The chemistry, physicochemical characteristics, and essential bioprofile of 21 qualifies it for serious consideration as a novel drug entity against hospital infections of multi-drug-resistant Staphylococcus aureus, and its progress up to clinical phase I trials in humans is described.