{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:58:55Z","timestamp":1790096335911,"version":"4.0.1"},"reference-count":21,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"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":[[2017,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Nafithromycin (WCK 4873), a novel antimicrobial agent of the lactone ketolide class, is currently in phase 2 development for treatment of community-acquired bacterial pneumonia (CABP). A total of 4,739 nonduplicate isolates were selected from a 2014 global surveillance program at medical institutions located in 43 countries within the United States, Europe, Latin America, and the Asia-Pacific region. Nafithromycin and comparator agents were used for susceptibility testing by reference broth microdilution methods. Nafithromycin was active against\n            <jats:named-content content-type=\"genus-species\">Staphylococcus aureus<\/jats:named-content>\n            (MIC\n            <jats:sub>50\/90<\/jats:sub>\n            , 0.06\/&gt;2 \u03bcg\/ml), including erythromycin-resistant strains exhibiting an inducible clindamycin resistance phenotype (MIC\n            <jats:sub>50\/90<\/jats:sub>\n            , 0.06\/0.06 \u03bcg\/ml) and telithromycin-susceptible strains (MIC\n            <jats:sub>50\/90<\/jats:sub>\n            , 0.06\/0.06 \u03bcg\/ml), but it exhibited limited activity against most telithromycin-resistant and clindamycin-resistant isolates that were constitutively resistant to macrolides (MIC\n            <jats:sub>50\/90<\/jats:sub>\n            , &gt;2\/&gt;2 \u03bcg\/ml). Nafithromycin was very active (MIC\n            <jats:sub>50\/90<\/jats:sub>\n            , 0.015\/0.06 \u03bcg\/ml) against 1,911\n            <jats:named-content content-type=\"genus-species\">Streptococcus pneumoniae<\/jats:named-content>\n            strains, inhibiting all strains, with MIC values of \u22640.25 \u03bcg\/ml. Telithromycin susceptibility was 99.9% for\n            <jats:named-content content-type=\"genus-species\">Streptococcus pneumoniae<\/jats:named-content>\n            strains, and nafithromycin was up to 8-fold more potent than telithromycin. Overall, 37.9% of\n            <jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>\n            strains were resistant to erythromycin, and 19.7% were resistant to clindamycin. Nafithromycin was highly active against 606\n            <jats:named-content content-type=\"genus-species\">Streptococcus pyogenes<\/jats:named-content>\n            strains (MIC\n            <jats:sub>50\/90<\/jats:sub>\n            , 0.015\/0.015 \u03bcg\/ml), inhibiting 100.0% of isolates at \u22640.5 \u03bcg\/ml, and MIC\n            <jats:sub>50\/90<\/jats:sub>\n            values (0.015\/0.015 to 0.03 \u03bcg\/ml) were similar for the 4 geographic regions. Nafithromycin and telithromycin demonstrated comparable\n            <jats:italic>in vitro<\/jats:italic>\n            activities against 1,002\n            <jats:named-content content-type=\"genus-species\">Haemophilus influenzae<\/jats:named-content>\n            isolates and 504\n            <jats:named-content content-type=\"genus-species\">Moraxella catarrhalis<\/jats:named-content>\n            isolates. Overall, nafithromycin showed potent\n            <jats:italic>in vitro<\/jats:italic>\n            activity against a broad range of contemporary (2014) global pathogens. These results support the continued clinical development of nafithromycin for treatment of CABP.\n          <\/jats:p>","DOI":"10.1128\/aac.01230-17","type":"journal-article","created":{"date-parts":[[2017,10,3]],"date-time":"2017-10-03T00:30:26Z","timestamp":1506990626000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["<i>In Vitro<\/i>\n            Activity of the Novel Lactone Ketolide Nafithromycin (WCK 4873) against Contemporary Clinical Bacteria from a Global Surveillance Program"],"prefix":"10.1128","volume":"61","author":[{"given":"R. K.","family":"Flamm","sequence":"first","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. R.","family":"Rhomberg","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. S.","family":"Sader","sequence":"additional","affiliation":[{"name":"JMI Laboratories, North Liberty, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"ASM Microbe","author":"Farrell DJ","year":"2016","unstructured":"Farrell DJ SaderHS RhombergPR FlammRK JonesRN. 2016. In vitro activity of lactone ketolide WCK 4873 when tested against contemporary community-acquired bacterial pneumonia pathogens from a global surveillance program, abstr Sunday-476. ASM Microbe, Boston, MA."},{"key":"e_1_3_2_3_2","volume-title":"ASM Microbe","author":"Farrell DJ","year":"2016","unstructured":"Farrell DJ SaderHS RhombergPR FlammRK JonesRN. 2016. In vitroactivity of WCK 4873 (nafithromycin) against resistant subsets of Streptococcus pneumoniae from a global surveillance program (2014), abstr Saturday-455. ASM Microbe, Boston, MA."},{"key":"e_1_3_2_4_2","volume-title":"ASM Microbe","author":"Chugh R","year":"2016","unstructured":"Chugh R GuptaM IwanowskiP BhatiaA. 2016. Nafithromycin phase 1 multiple ascending dose study in healthy subjects, abstr Monday-513. ASM Microbe, Boston, MA."},{"key":"e_1_3_2_5_2","volume-title":"ASM Microbe","author":"Bhatia A","year":"2016","unstructured":"Bhatia A ChughR GuptaM IwanowskiP. 2016. Nafithromycin single ascending dose (SAD) and food effect (FE) study in healthy subjects, abstr Monday-514. ASM Microbe, Boston, MA."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200262120-00006"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01994-13"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02316-12"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-0691.2001.0070s3011.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2016.08.035"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1089\/sur.2015.209"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1086\/511159"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2012.08.024"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03172-14"},{"key":"e_1_3_2_15_2","volume-title":"Antibiotic resistance threats in the United States","author":"CDC","year":"2013","unstructured":"CDC. 2013. Antibiotic resistance threats in the United States. CDC, Atlanta, GA."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2006.01395.x"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22620"},{"key":"e_1_3_2_18_2","volume-title":"ECCMID","author":"Khande H","year":"2017","unstructured":"Khande H SatavJ KulkarniA BhagwatS PatelM. 2017. WCK 4873 (nafithromycin): impact of hyper ermB induction in S. pneumoniae and S. aureus on the activity of ketolides, abstr P1350. ECCMID, Vienna, Austria."},{"key":"e_1_3_2_19_2","volume-title":"ASM Microbe","author":"Chugh R","year":"2016","unstructured":"Chugh R BhatiaA GuptaM SharmaN GotfriedM RodvoldK. 2016. Nafithromycin (WCK 4873) concentrations in plasma, epithelial lining fluid, and alveolar macrophages of healthy subjects, abstr Monday-506. ASM Microbe, Boston, MA."},{"key":"e_1_3_2_20_2","volume-title":"M07-A10","author":"CLSI","year":"2015","unstructured":"CLSI. 2015. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard\u201410th ed. M07-A10. Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_2_21_2","volume-title":"Performance standards for antimicrobial susceptibility testing: 26th informational supplement","author":"CLSI","year":"2016","unstructured":"CLSI. 2016. M100-S26. Performance standards for antimicrobial susceptibility testing: 26th informational supplement. Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_2_22_2","unstructured":"EUCAST. 2016. Breakpoint tables for interpretation of MICs and zone diameters. Version 6.0 January 2016. European Committee on Antimicrobial Susceptibility Testing. http:\/\/www.eucast.org\/fileadmin\/src\/media\/PDFs\/EUCAST_files\/Breakpoint_tables\/v_6.0_Breakpoint_table.xls."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01230-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01230-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:45:38Z","timestamp":1645476338000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01230-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12]]},"references-count":21,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["10.1128\/AAC.01230-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.01230-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12]]},"assertion":[{"value":"2017-06-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-09-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-11-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01230-17"}}