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For 302 methicillin-susceptible strains the MIC at which 50% of isolates are inhibited (MIC<jats:sub>50<\/jats:sub>) and the MIC<jats:sub>90<\/jats:sub>of WCK 771 were 0.03 and 0.03 \u03bcg\/ml, respectively, and for 198 methicillin-resistant strains the MIC<jats:sub>50<\/jats:sub>and the MIC<jats:sub>90<\/jats:sub>were 0.5 and 1.0 \u03bcg\/ml, respectively. All methicillin-susceptible staphylococci were quinolone susceptible, and almost all methicillin-resistant staphylococci were quinolone resistant. WCK 771 was more potent than moxifloxacin, trovafloxacin, levofloxacin, and ciprofloxacin and had potency comparable to that of clinafloxacin. Only WCK 771 and clinafloxacin demonstrated strong potencies against vancomycin-intermediate<jats:italic>Staphylococcus aureus<\/jats:italic>strains (MICs = 1 \u03bcg\/ml). WCK 771 is not a substrate of the NorA pump, as evident from the lack of an effect of reserpine on the MICs and similar protective doses against infections caused by efflux-positive and -negative staphylococci. WCK 771 was effective by both the oral and the subcutaneous routes in mice infected intraperitoneally with quinolone-susceptible methicillin-susceptible<jats:italic>S. aureus<\/jats:italic>(MSSA) strains. For infections caused by quinolone-resistant methicillin-resistant<jats:italic>S. aureus<\/jats:italic>(MRSA) strains, the activity of WCK 771 administered subcutaneously was superior to those of trovafloxacin and sparfloxacin, with a 50% effective dose range of 27.8 to 46.8 mg\/kg of body weight. The activity of WCK 771 was superior to those of moxifloxacin, vancomycin, and linezolid in a mouse cellulitis model of infection caused by one MSSA and two MRSA strains, with effective doses of 2.5 and 5 mg\/kg for the MSSA strain and 10-fold higher effective doses for MRSA strains. WCK 771, like vancomycin and linezolid, eradicated MRSA from mouse liver, spleen, kidney, and lung when it was administered subcutaneously at a dose of 50 mg\/kg for four doses. These studies have demonstrated the effectiveness of WCK 771, administered orally and parenterally, for the treatment of diverse staphylococcal infections in mice, including those caused by quinolone-resistant strains.<\/jats:p>","DOI":"10.1128\/aac.48.12.4754-4761.2004","type":"journal-article","created":{"date-parts":[[2004,11,24]],"date-time":"2004-11-24T03:00:46Z","timestamp":1101265246000},"page":"4754-4761","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":39,"title":["Antistaphylococcal Activity of WCK 771, a Tricyclic Fluoroquinolone, in Animal Infection Models"],"prefix":"10.1128","volume":"48","author":[{"given":"Mahesh V.","family":"Patel","sequence":"first","affiliation":[{"name":"Wockhardt Research Center, Aurangabad, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel J.","family":"De Souza","sequence":"additional","affiliation":[{"name":"Wockhardt Research Center, Aurangabad, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shrikant V.","family":"Gupte","sequence":"additional","affiliation":[{"name":"Wockhardt Research Center, Aurangabad, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad A.","family":"Jafri","sequence":"additional","affiliation":[{"name":"Wockhardt Research Center, Aurangabad, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachin S.","family":"Bhagwat","sequence":"additional","affiliation":[{"name":"Wockhardt Research Center, Aurangabad, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yati","family":"Chugh","sequence":"additional","affiliation":[{"name":"Wockhardt Research Center, Aurangabad, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Habil F.","family":"Khorakiwala","sequence":"additional","affiliation":[{"name":"Wockhardt Research Center, Aurangabad, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Appelbaum","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hershey Medical Center, Hershey, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.2.335"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1093\/jac\/dkf155","volume":"50","year":"2002","unstructured":"Boswell, F. 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