In Vitro Activity of the Quinolone WCK 771 against Recent U.S. Hospital and Community-Acquired Staphylococcus aureus Pathogens with Various Resistance Types

Abstract

WCK 771 demonstrated MIC 50 and MIC 90 s of 0.03 and 1 g/ml, respectively, against 297 recent U.S. community-acquired and hospital strains of Staphylococcus aureus, irrespective of quinolone or glycopeptide resistance. Against quinolone-resistant strains, MIC 90 s of WCK 771 and moxifloxacin were 1 and 16 g/ml, respectively.Methicillin-resistant Staphylococcus aureus (MRSA) accounts for approximately 48 to 60% of the staphylococcal strains isolated from inpatients and outpatients in the United States, with Ͼ50% being multidrug resistant (17). Recently, the epidemiology of MRSA has changed, with emergence of quinolone-resistant community-acquired and multidrug-resistant hospital-acquired MRSA strains. Additionally, recognition of heteroresistant vancomycin-intermediate S. aureus (hVISA), vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant S. aureus (VRSA) has caused concern; hVISA and VISA strains have been associated with vancomycin clinical failures (1,7,16). Compromised activity against VISA (10) and lack of broad-spectrum activity and bacteriostatic action are limitations of the currently employed anti-MRSA agents and point toward the need for new alternatives from other antibacterial classes.The increase in quinolone resistance among methicillin-susceptible S. aureus (MSSA) and lack of sufficient activity against MRSA have compromised the therapeutic utility of all clinically available quinolones for the treatment of staphylococcal infections (5, 13). WCK 771 is a broad-spectrum intravenous quinolone active against MRSA and quinolone-resistant S. aureus and is currently being studied in phase 2 clinical trials (2,8,14). Its oral form is under development in phase 1 clinical studies. The present study was undertaken to establish the in vitro activity of WCK 771 against recent (2005 to 2007) U.S. clinical isolates of S. aureus with various resistance phenotypes, including vancomycin nonsusceptibility, originating from community and hospital settings and to determine its activity relative to currently utilized anti-MRSA agents, such as vancomycin. Moxifloxacin was included as a comparator quinolone, since among approved quinolones it shows significantly improved activity against S. aureus and possesses a superior pharmacokinetic-pharmacodynamic profile compared to other available quinolones.(Portions of this work were previously presented at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 2007 [12].)A total of 101 methicillin-susceptible and 196 methicillinresistant strains were tested: 110 isolates were hospital acquired. Among 86 community-acquired MRSA strains, 73 produced Panton-Valentin leukocidin as identified by PCR using methods described previously (11); 2 hVISA, 25 VISA, and 7 VRSA strains were also included in the study. Vancomycin-susceptible strains were isolated in Pennsylvania, Texas, and Ohio, and a few strains were from western Europe. Both hVISA isolates were obtained from sputum of patients at Hershey Medical Center (HMC) who had received...

In Vitro Antibacterial Activities of JNJ-Q2, a New Broad-Spectrum Fluoroquinolone

“…In contemporary surveillance studies of health care-associated MRSA isolates, the rate of ciprofloxacin resistance is routinely reported to be Ն50%, and currently approved fluoroquinolones are indicated for use only for the treatment of staphylococcal infections mediated by methicillin-susceptible strains. However, a series of investigational fluoroquinolones have been reported to exhibit good in vitro activities against MRSA, including ciprofloxacin-resistant strains (2,5,25,29,45), and several of these agents are reported to be undergoing clinical evaluation for the treatment of complicated skin and skin structure infections (cSSSIs), including infections caused by MRSA strains.…”

In Vitro Activities of the Benzoquinolizine Fluoroquinolone Levonadifloxacin (WCK 771) and Other Antimicrobial Agents against Mycoplasmas and Ureaplasmas in Humans, Including Isolates with Defined Resistance Mechanisms

“…L evonadifloxacin (WCK 771) and its oral prodrug alalevonadifloxacin (WCK 2349) are being developed by Wockhardt Bio AG for the treatment of acute bacterial skin and soft tissue infections, community-acquired bacterial pneumonias, and other types of infections. In vitro data indicate that levonadifloxacin has a broad spectrum of in vitro activity against Gram-positive and Gram-negative bacteria, including fluoroquinoloneresistant staphylococci (1). In addition to the bacterial species already evaluated, it is important to determine the in vitro activity of levonadifloxacin against other important pathogens of the urogenital and respiratory tracts, including Mycoplasma and Ureaplasma spp.…”

In Vitro Activity of Ozenoxacin against Quinolone-Susceptible and Quinolone-Resistant Gram-Positive Bacteria

“…However, the emergence of resistant strains has compromised the clinical usefulness of quinolones currently available for the treatment of staphylococcal infections (3,5,6). The emergence of resistance has made it necessary to design new drugs for the treatment of infections caused by resistant strains.…”

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