{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:01:44Z","timestamp":1791414104243,"version":"4.3.3"},"reference-count":56,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2018,3,27]],"date-time":"2018-03-27T00:00:00Z","timestamp":1522108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["086065"],"award-info":[{"award-number":["086065"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["090640"],"award-info":[{"award-number":["090640"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Increasing antimicrobial resistance among uropathogens limits treatment options for patients with complicated urinary tract infection (cUTI). Plazomicin, a new aminoglycoside, has\n                    <jats:italic>in vitro<\/jats:italic>\n                    activity against multidrug-resistant\n                    <jats:named-content content-type=\"genus-species\">Enterobacteriaceae<\/jats:named-content>\n                    , including isolates resistant to currently available aminoglycosides, as well as extended-spectrum \u03b2-lactamase-producing and carbapenem-resistant\n                    <jats:named-content content-type=\"genus-species\">Enterobacteriaceae<\/jats:named-content>\n                    . We evaluated the efficacy and safety of plazomicin in a double-blind, comparator-controlled, phase 2 study in adults with cUTI or acute pyelonephritis. Patients were randomized 1:1:1 to receive intravenous plazomicin (10 or 15 mg\/kg of body weight) or intravenous levofloxacin (750 mg) once daily for 5 days. Coprimary efficacy endpoints were microbiological eradication at the test of cure (TOC; 5 to 12 days after the last dose) in the modified intent-to-treat (MITT) and microbiologically evaluable (ME) populations. Overall, 145 patients were randomized to treatment. In the groups receiving plazomicin at 10 mg\/kg, plazomicin at 15 mg\/kg, and levofloxacin, microbiological eradication rates were, respectively, 50.0% (6 patients with microbiological eradication at TOC\/12 patients treated [95% confidence interval {CI}, 21.1 to 78.9%]), 60.8% (31\/51 [95% CI, 46.1 to 74.2%]), and 58.6% (17\/29 [95% CI, 38.9 to 76.5%]) in the MITT population and 85.7% (6\/7 [95% CI, 42.1 to 99.6%]), 88.6% (31\/35 [95% CI, 73.3 to 96.8%]), and 81.0% (17\/21 [95% CI, 58.1 to 94.6%]) in the ME population. In the MITT population, 66.7% (95% CI, 34.9 to 90.1%), 70.6% (95% CI, 56.2 to 82.5%), and 65.5% (95% CI, 45.7 to 82.1%) of the patients in the three groups, respectively, were assessed by the investigator to be clinically cured at TOC. Adverse events were reported in 31.8%, 35.1%, and 47.7% of the patients in the three groups, respectively. Serum creatinine values were generally stable over the course of the study. No plazomicin-treated patients with evaluable audiometry data had postbaseline sensorineural, conductive, or mixed hearing loss. In summary, plazomicin demonstrated microbiological and clinical success and an overall safety profile supportive of further clinical development. (This study has been registered at ClinicalTrials.gov under identifier NCT01096849.)\n                  <\/jats:p>","DOI":"10.1128\/aac.01989-17","type":"journal-article","created":{"date-parts":[[2018,1,27]],"date-time":"2018-01-27T06:28:15Z","timestamp":1517034495000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":79,"title":["A Multicenter, Randomized, Double-Blind, Phase 2 Study of the Efficacy and Safety of Plazomicin Compared with Levofloxacin in the Treatment of Complicated Urinary Tract Infection and Acute Pyelonephritis"],"prefix":"10.1128","volume":"62","author":[{"given":"Lynn E.","family":"Connolly","sequence":"first","affiliation":[{"name":"Achaogen, Inc., South San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Riddle","sequence":"additional","affiliation":[{"name":"BioPharmAdvisors LLC, Parrish, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Cebrik","sequence":"additional","affiliation":[{"name":"Achaogen, Inc., South San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana S.","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Achaogen, Inc., South San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loren G.","family":"Miller","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine, University of California, Los Angeles, Los Angeles BioMedical Research at Harbor-UCLA Medical Center, Torrance, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2013.9763"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2013.09.003"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1155\/2005\/385768"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-013-1218-9"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2015.199"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.2174\/1874285801206010074"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2012.05.024"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2016.04.022"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-013-1154-8"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis942"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.12480"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2209.160148"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13893"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2016.09.003"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/jhm.2157"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-017-2383-z"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01041-09"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkm318"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2012.10.028"},{"key":"e_1_3_3_21_2","volume-title":"Antibiotic resistance threats in the United States, 2013","author":"U.S. Department of Health and Human Services, Centers for Disease Control and Prevention","year":"2013","unstructured":"U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. 2013. Antibiotic resistance threats in the United States, 2013. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Atlanta, GA."},{"key":"e_1_3_3_22_2","volume-title":"Antimicrobial resistance: global report on surveillance","author":"World Health Organization","year":"2014","unstructured":"World Health Organization. 2014. Antimicrobial resistance: global report on surveillance. World Health Organization, Geneva, Switzerland."},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn469"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1445-5994.2011.02452.x"},{"key":"e_1_3_3_25_2","volume-title":"Guidelines on urological infections","author":"Grabe M","unstructured":"Grabe M, Bartoletti R, Bjerklund-Johansen TE, Cai T, Cek M, Koves B, Naber K, Pickard RS, Tenke P, Wagenlehner C, Wullt B. Guidelines on urological infections. European Association of Urology, Arnhem, The Netherlands. http:\/\/uroweb.org\/wp-content\/uploads\/19-Urological-infections_LR2.pdf. Accessed 29 September 2016."},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq298"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1086\/520991"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(90)90099-Y"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.312.7027.338"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.7.1549"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkm193"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00572-10"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1586\/eri.12.25"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq278"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00869-16"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02454-16"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02744-13"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1179\/1973947812Y.0000000015"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00099-14"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00641-09"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq408"},{"key":"e_1_3_3_42_2","volume-title":"Abstr 52nd Intersci Conf Antimicrob Agents Chemother","author":"Riddle VD","year":"2012","unstructured":"Riddle VD, Cebrik DS, Armstrong ES, Cass RT, Clobes TC, Hillan KJ. 2012. Plazomicin safety and efficacy in patients with complicated urinary tract infection (cUTI) or acute pyelonephritis (AP). Abstr 52nd Intersci Conf Antimicrob Agents Chemother, San Francisco, CA, abstr L2-2118a."},{"key":"e_1_3_3_43_2","volume-title":"Document M100-S22","author":"Clinical and Laboratory Standards Institute","year":"2012","unstructured":"Clinical and Laboratory Standards Institute. 2012. Performance standards for antimicrobial susceptibility testing; 22nd informational supplement. Document M100-S22. Clinical and Laboratory Standards Institute, Wayne, PA."},{"key":"e_1_3_3_44_2","unstructured":"European Committee on Antimicrobial Susceptibility Testing. 2012. Breakpoint tables for interpretation of MICs and zone diameter version 2.0. http:\/\/www.eucast.org\/fileadmin\/src\/media\/PDFs\/EUCAST_files\/Breakpoint_tables\/Breakpoint_table_v_2.0_120221.pdf. Accessed 25 October 2017."},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03570.x"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.03.050"},{"key":"e_1_3_3_47_2","first-page":"S149","article-title":"Isepamicin versus amikacin in the treatment of urinary tract infection","volume":"7","author":"Sturm W","year":"1995","unstructured":"Sturm W. 1995. Isepamicin versus amikacin in the treatment of urinary tract infection. J Chemother 7(Suppl 2):S149\u2013S154.","journal-title":"J Chemother"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiac.2014.08.007"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw378"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)62220-0"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-015-1282-4"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1080\/00325481.2017.1246055"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.19.1.147"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00624-11"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1086\/650482"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.57.1.22"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01989-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01989-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T16:12:57Z","timestamp":1645459977000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01989-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4]]},"references-count":56,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1128\/AAC.01989-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.01989-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4]]},"assertion":[{"value":"2017-09-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01989-17"}}