{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T14:17:14Z","timestamp":1781273834467,"version":"3.54.1"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2017,7,1]],"date-time":"2017-07-01T00:00:00Z","timestamp":1498867200000},"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":[[2017,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Shigella flexneri<\/jats:named-content>\n            continues to be a major cause of diarrhea-associated illness, and increasing resistance to first-line antimicrobials complicates the treatment of infections caused by this pathogen. We investigated the pharmacodynamics of current antimicrobial treatments for shigellosis to determine the likelihood of resistance promotion with continued global antimicrobial use. The mutant prevention concentration (MPC) and mutant selection window (MSW) were determined for azithromycin, ceftriaxone, ciprofloxacin, levofloxacin, and moxifloxacin against a wild-type strain of\n            <jats:named-content content-type=\"genus-species\">S. flexneri<\/jats:named-content>\n            (ATCC 12022) and an isogenic\n            <jats:italic>gyrA<\/jats:italic>\n            mutant (m-12022). Time-kill assays were performed to determine antimicrobial killing. Concentrations of approved doses of ciprofloxacin, levofloxacin, and moxifloxacin are predicted to surpass the MPC for a majority of the dosage interval against ATCC 12022. However, against m-12022, concentrations of all fluoroquinolones are predicted to fall below the MPC and remain in the MSW for a majority of the dosage interval. Concentrations of ceftriaxone fall within the MSW for the majority of the dosage interval for both strains. All agents other than azithromycin displayed bactericidal activity in time-kill assays. Results of pharmacodynamic analyses suggest that all tested fluoroquinolones would achieve a favorable area under the concentration-time curve (AUC)\/MPC ratio for ATCC 12022 and would restrict selective enrichment of mutants but that mutant selection in m-12022 would be likely if ciprofloxacin were used. Based on pharmacodynamic analyses, azithromycin and ceftriaxone are predicted to promote mutant selection in both strains. Confirmation of these findings and examination of novel treatment regimens using\n            <jats:italic>in vivo<\/jats:italic>\n            studies are warranted.\n          <\/jats:p>","DOI":"10.1128\/aac.00086-17","type":"journal-article","created":{"date-parts":[[2017,5,9]],"date-time":"2017-05-09T00:40:16Z","timestamp":1494290416000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["<i>In Vitro<\/i>\n            Resistance Selection in Shigella flexneri by Azithromycin, Ceftriaxone, Ciprofloxacin, Levofloxacin, and Moxifloxacin"],"prefix":"10.1128","volume":"61","author":[{"given":"George P.","family":"Allen","sequence":"first","affiliation":[{"name":"University of New England College of Pharmacy, Portland, Maine, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla A.","family":"Harris","sequence":"additional","affiliation":[{"name":"University of New England College of Pharmacy, Portland, Maine, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.2015.983902"},{"key":"e_1_3_2_3_2","first-page":"495","article-title":"Preliminary incidence and trends of infection with pathogens transmitted commonly through food\u2014Foodborne Diseases Active Surveillance Network, 10 U.S. sites, 2006\u20132014","volume":"64","author":"Crim SM","year":"2015","unstructured":"Crim SM GriffinPM TauxeR MarderEP GillissD CronquistAB CartterM Tobin-D'AngeloM BlytheD SmithK LathropS ZanskyS CieslakPR DunnJ HoltKG WolpertB HenaoOL. 2015. Preliminary incidence and trends of infection with pathogens transmitted commonly through food\u2014Foodborne Diseases Active Surveillance Network, 10 U.S. sites, 2006\u20132014. MMWR Morb Mortal Wkly Rep64:495\u2013499.","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/318514"},{"key":"e_1_3_2_5_2","volume-title":"Guidelines for the control of shigellosis, Including epidemics due to Shigella dysenteriae type 1, 2005","author":"WHO","year":"2005","unstructured":"WHO. 2005. Guidelines for the control of shigellosis, Including epidemics due to Shigella dysenteriae type 1, 2005. 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M100-S26. Performance standards for antimicrobial susceptibility testing: 26th informational supplement. Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_2_26_2","unstructured":"EUCAST. 2017. Breakpoint tables for interpretation of MICs and zone diameters. Version 7.0 January 2017. http:\/\/www.eucast.org\/clinical_breakpoints\/. Accessed January 2017."},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0000000000000096"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-013-1937-2"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.4103\/0255-0857.55460"},{"key":"e_1_3_2_30_2","first-page":"1619","article-title":"Emergence of Shigella flexneri 2a resistant to ceftriaxone and ciprofloxacin\u2014South Carolina, October 2010","volume":"59","author":"Jue S","year":"2010","unstructured":"Jue S HardeeR OvermanM MaysE BowenA WhichardJ GreeneK PecicG TaylorE. 2010. 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