{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:44:30Z","timestamp":1784735070399,"version":"3.55.0"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"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":[[2024,11,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              High-dose levofloxacin was explored in a clinical trial against multidrug-resistant tuberculosis and failed to show increased efficacy. In this study, we used a murine model to explore the efficacy of a dose increase in levofloxacin monotherapy beyond the maximum dose evaluated in humans. A total of 120 4-week-old female BALB\/c mice were intravenously infected with 10\n              <jats:sup>6<\/jats:sup>\n              CFU of\n              <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n              H37Rv wild-type (WT) or isogenic H37Rv mutants harboring GyrA A90V or D94G substitutions; the MICs were 0.25, 4, and 6 \u00b5g\/mL, respectively. Levofloxacin 250 and 500 mg\/kg were given every 12 h (q12h) orally for 4 weeks. Pharmacokinetic parameters were determined after five doses. These two regimens decreased lung bacillary load in mice infected with H37Rv WT but not in mice infected with the A90V and D94G mutants. Levofloxacin 250 mg\/kg q12h in mice generated pharmacokinetic parameters equivalent to 1,000 mg\/d in humans, whereas 500 mg\/kg q12h generated a twofold greater exposure than the highest equivalent dose tested in humans (1,500 mg\/d). In our dose\u2013response model, the effective concentration at 50% (EC\n              <jats:sub>50<\/jats:sub>\n              ) produced an AUC\/MIC (AUC\n              <jats:sub>0\u201324h<\/jats:sub>\n              \/MIC) ratio of 167.9 \u00b1 27.5, and at EC\n              <jats:sub>80<\/jats:sub>\n              it was 281.2 \u00b1 97.3. Based on this model, high-dose levofloxacin regimens above 1,000 mg\/d are not expected to cause a significant increase in bactericidal activity. This study suggests no benefit of high-dose levofloxacin above 1,000 mg\/d in the treatment of fluoroquinolone-susceptible or -resistant tuberculosis.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00583-24","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T12:56:27Z","timestamp":1729083387000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Levofloxacin activity at increasing doses in a murine model of fluoroquinolone-susceptible and -resistant tuberculosis"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5463-336X","authenticated-orcid":true,"given":"Thomas","family":"Maitre","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), UMR 1135, Paris, France"},{"name":"Department of Pneumology and Reference Centre for Rare Lung Diseases, Assistance Publique H\u00f4pitaux de Paris, Tenon Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Godmer","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), UMR 1135, Paris, France"},{"name":"F\u00e9d\u00e9ration de Bact\u00e9riologie, Centre National de R\u00e9f\u00e9rence des Mycobact\u00e9ries, APHP, Sorbonne Universit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Mory","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Microbiologie Clinique et Dosage des Anti-infectieux, Groupe Hospitalier Paris-Saint-Joseph, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Chauffour","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), UMR 1135, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi Cuc","family":"Mai","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), UMR 1135, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najoua","family":"El Helali","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Microbiologie Clinique et Dosage des Anti-infectieux, Groupe Hospitalier Paris-Saint-Joseph, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Aubry","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), UMR 1135, Paris, France"},{"name":"F\u00e9d\u00e9ration de Bact\u00e9riologie, Centre National de R\u00e9f\u00e9rence des Mycobact\u00e9ries, APHP, Sorbonne Universit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Veziris","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Centre d'Immunologie et des Maladies Infectieuses (Cimi-Paris), UMR 1135, Paris, France"},{"name":"F\u00e9d\u00e9ration de Bact\u00e9riologie, Centre National de R\u00e9f\u00e9rence des Mycobact\u00e9ries, APHP, Sorbonne Universit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2117166"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01883-9"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2033400"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1407426"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00968-10"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00506-13"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx150"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy611"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/resp.13452"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00537-2018"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1534"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201303-0604OC"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00770-18"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-017-2292-x"},{"key":"e_1_3_4_18_2","first-page":"217","article-title":"Measurement of sensitivity of the tuberculous bacillus to antibacillary drugs by the method of proportions","volume":"27","author":"Canetti G","year":"1963","unstructured":"Canetti G, Rist N, Grosset J. 1963. Measurement of sensitivity of the tuberculous bacillus to antibacillary drugs by the method of proportions. Rev Tuberc Pneumol 27:217\u2013272.","journal-title":"Rev Tuberc Pneumol"},{"key":"e_1_3_4_19_2","first-page":"1","volume-title":"Guideline on bioanalytical method validation EMEA\/CHMP\/EWP\/192217\/2009","author":"European Medicines Agency (EMA)","year":"2015","unstructured":"European Medicines Agency (EMA). 2015. Guideline on bioanalytical method validation EMEA\/CHMP\/EWP\/192217\/2009, p 1\u201323. European Medicines Agency."},{"key":"e_1_3_4_20_2","volume-title":"R: a language and environment for statistical computing","author":"R Core Team","year":"2018","unstructured":"R Core Team. 2018. R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria."},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(16)30274-2"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201407-1264OC"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00414-06"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01092-18"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.300.18.2153"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31644-1"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1089\/mdr.2006.12.7"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.1.104-112.2006"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0120470"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw344"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00217-12"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02516-18"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005650"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00583-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00583-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T13:03:22Z","timestamp":1730898202000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00583-24"}},"subtitle":[],"editor":[{"given":"Sean","family":"Wasserman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,11,6]]},"references-count":30,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11,6]]}},"alternative-id":["10.1128\/aac.00583-24"],"URL":"https:\/\/doi.org\/10.1128\/aac.00583-24","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,6]]},"assertion":[{"value":"2024-04-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00583-24"}}