{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T01:22:02Z","timestamp":1773796922273,"version":"3.50.1"},"reference-count":17,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2000,4,1]],"date-time":"2000-04-01T00:00:00Z","timestamp":954547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2000,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n To demonstrate the impact of the pharmacokinetics of gatifloxacin (GA) relative to those of ciprofloxacin (CI) on the antimicrobial effect (AME), the killing and regrowth kinetics of two differentially susceptible clinical isolates each of\n Staphylococcus aureus<\/jats:italic>\n ,\n Escherichia coli<\/jats:italic>\n , and\n Klebsiella pneumoniae<\/jats:italic>\n were studied. With each organism, a series of monoexponential pharmacokinetic profiles of GA (half-life [\n t<\/jats:italic>\n 1\/2<\/jats:sub>\n ], 7 h) and CI (\n t<\/jats:italic>\n 1\/2<\/jats:sub>\n = 4 h) were simulated to mimic different single doses of GA and two 12-h doses of CI. The respective eightfold ranges of the ratios of the area under the concentration-time curve (AUC) to the MIC were 58 to 466 and 116 to 932 (\u03bcg \u00b7 h\/ml)\/(\u03bcg\/ml). The species- and strain-independent linear relationships observed between the intensity of AME (\n \n I\n E<\/jats:sub>\n <\/jats:italic>\n ) and log AUC\/MIC were not superimposed for GA and CI (\n r<\/jats:italic>\n 2<\/jats:sup>\n = 0.99 in both cases). The predicted AUC\/MIC ratio for GA that might be equivalent to a clinically relevant AUC\/MIC breakpoint for CI was estimated to be 102 rather than 125 (\u03bcg \u00b7 h\/ml)\/(\u03bcg\/ml). The respective MIC breakpoints were 0.32 \u03bcg\/ml (for a 400-mg dose of GA) and 0.18 \u03bcg\/ml (for two 500-mg doses of CI). On the basis of the\n \n I\n E<\/jats:sub>\n <\/jats:italic>\n -log AUC\/MIC relationships, equiefficient 24-h doses (\n D<\/jats:italic>\n 24h<\/jats:sub>\n s) of GA and CI were calculated for hypothetical strains of\n S. aureus<\/jats:italic>\n ,\n E. coli<\/jats:italic>\n , and\n K. pneumoniae<\/jats:italic>\n for which the MICs were equal to the MICs at which 50% of isolates are inhibited. To provide an \u201cacceptable\u201d\n \n I\n E<\/jats:sub>\n <\/jats:italic>\n equal to 200 (log CFU\/ml) \u00b7 h, i.e., the\n \n I\n E<\/jats:sub>\n <\/jats:italic>\n provided by AUC\/MIC of 125 (\u03bcg \u00b7 h\/ml)\/(\u03bcg\/ml) for ciprofloxacin, the\n D<\/jats:italic>\n 24h<\/jats:sub>\n s of GA for all three organisms were much lower (115, 30, and 60 mg) than the clinically proposed 400-mg dose. Although the usual dose of CI (two doses of 500 mg) would be in excess for\n E. coli<\/jats:italic>\n and\n K. pneumoniae<\/jats:italic>\n (\n D<\/jats:italic>\n 24h<\/jats:sub>\n = two doses of 40 mg and two doses of 115 mg, respectively), even the highest clinical dose of CI (two doses of 750 mg) might be insufficient for\n S. aureus<\/jats:italic>\n (\n D<\/jats:italic>\n 24h<\/jats:sub>\n , > two doses of 1,000 mg). The method of generalization of data obtained with specific organisms to other representatives of the same species described in the present report might be useful for prediction of the AMEs of new quinolones.\n <\/jats:p>","DOI":"10.1128\/aac.44.4.879-884.2000","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:06:42Z","timestamp":1027764402000},"page":"879-884","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["Comparative Pharmacodynamics of Gatifloxacin and Ciprofloxacin in an In Vitro Dynamic Model: Prediction of Equiefficient Doses and the Breakpoints of the Area under the Curve\/MIC Ratio"],"prefix":"10.1128","volume":"44","author":[{"given":"Sergey N.","family":"Vostrov","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Roger Williams Medical Center, Rhode Island Hospital, Brown University, Providence, Rhode Island"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga V.","family":"Kononenko","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Roger Williams Medical Center, Rhode Island Hospital, Brown University, Providence, Rhode Island"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene Y.","family":"Lubenko","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Roger Williams Medical Center, Rhode Island Hospital, Brown University, Providence, Rhode Island"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen H.","family":"Zinner","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Roger Williams Medical Center, Rhode Island Hospital, Brown University, Providence, Rhode Island"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander A.","family":"Firsov","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Roger Williams Medical Center, Rhode Island Hospital, Brown University, Providence, Rhode Island"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/40.5.639"},{"key":"e_1_3_2_3_2","unstructured":"Bergan\n T.\n Thorsteinsson\n S. B.\n Pharmacokinetics and bioavailability of ciprofloxacin\n Proceedings of the 1st International Ciprofloxacin Workshop Current Clinical Practice series 34.\n Neu\n H. C.\n Weuta\n H.\n 1986\n 111\n 121\n Elsevier Science Publishers B.V. (Excerpta Medica)\n Amsterdam The Netherlands"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1093\/jac\/39.suppl_2.43","article-title":"In-vitro activity of trovafloxacin, a new fluoroquinolone, against recent clinical isolates.","volume":"39","author":"Felmingham D.","year":"1997","unstructured":"Felmingham D. Robbins M. J. Ingley K. Mathias I. Bhogal H. A. Leakey G. L. Ridgway G. L. Gr\u00fcneberg R. N. In-vitro activity of trovafloxacin, a new fluoroquinolone, against recent clinical isolates. J. Antimicrob. Chemother. 39 (Suppl. B) 1997 43 49","journal-title":"J. Antimicrob. Chemother."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.34.7.1312"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.3.734"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.3.659"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1093\/jac\/43.4.483","article-title":"Prediction of the antimicrobial effects of trovafloxacin and ciprofloxacin on staphylococci using an in-vitro dynamic model.","volume":"43","author":"Firsov A. A.","year":"1999","unstructured":"Firsov A. A. Vostrov S. N. Kononenko O. V. Lubenko I. Y. Zinner S. H. Prediction of the antimicrobial effects of trovafloxacin and ciprofloxacin on staphylococci using an in-vitro dynamic model. J. Antimicrob. Chemother. 43 1999 483 490","journal-title":"J. Antimicrob. Chemother."},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.6.1281"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.11.2841"},{"key":"e_1_3_2_11_2","unstructured":"Grasela\n D. M.\n Nakashima\n M.\n Uematsu\n T.\n Pharmacokinetics of BMS-206584; 200 mg oral dose with concurrent probenecid in humans. Report no. 910058296.\n 1996\n Bristol-Myers Squibb Pharmaceutical Research Institute"},{"key":"e_1_3_2_12_2","unstructured":"Grasela\n D. M.\n Nakashima\n M.\n Uematsu\n T.\n Phase I trial of a single intravenous infusion of BMS-206584 (AM-1155) in healthy male volunteers. Report no. 910058297.\n 1996\n Bristol-Myers Squibb Pharmaceutical Research Institute"},{"key":"e_1_3_2_13_2","unstructured":"Grasela\n D. M.\n Uematsu\n T.\n Nakashima\n M.\n Oral dose phase I study of AM-1155 (BMS-206584). Report no. 910058295.\n 1996\n Bristol-Myers Squibb Pharmaceutical Research Institute"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.27.3.375"},{"key":"e_1_3_2_15_2","unstructured":"Schentag\n J. J.\n Nix\n D. E.\n Forrest\n A.\n Pharmacodynamics of the fluoroquinolones\n Quinolone antimicrobial agents\n 2nd ed.\n Hooper\n D. C.\n Wolfson\n J. S.\n 1993\n 259\n 271\n American Society for Microbiology\n Washington D.C."},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1093\/jac\/39.suppl_2.57","article-title":"The in-vitro activity of trovafloxacin, a new fluoroquinolone, against gram-positive bacteria.","volume":"39","author":"Seftone A. M.","year":"1997","unstructured":"Seftone A. M. Maskell J. P. Rafay A. M. Whiley A. Williams J. D. The in-vitro activity of trovafloxacin, a new fluoroquinolone, against gram-positive bacteria. J. Antimicrob. Chemother. 39 (Suppl. B) 1997 57 62","journal-title":"J. Antimicrob. 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