{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T07:44:13Z","timestamp":1777794253176,"version":"3.51.4"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2021,7,10]],"date-time":"2021-07-10T00:00:00Z","timestamp":1625875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Northstate University College of Pharmacy"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01AI148560"],"award-info":[{"award-number":["R01AI148560"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Enterococcus faecalis commonly produce aminoglycoside-modifying enzymes (AMEs) and are implicated in polymicrobial infections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To determine if AME-producing E. faecalis is capable of protecting Enterobacteriaceae and Pseudomonas aeruginosa from gentamicin exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two Klebsiella pneumoniae isolates, two Escherichia coli isolates, and two Pseudomonas aeruginosa isolates were investigated in monoculture time\u2013kill experiments, and each Gram-negative organism was also evaluated during co-culture with either AME-producing or AME-deficient E. faecalis. A pharmacokinetic\/pharmacodynamics analysis that utilized Log Ratio Areas and a Hill-type mathematical model was used to determine if the maximal killing or potency of gentamicin against the Gram-negative organisms was altered by the presence of the E. faecalis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The maximal killing and potency of gentamicin was the same during monoculture and co-culture experiments for both K. pneumoniae isolates and one E. coli isolate (P\u200a&amp;gt;\u200a0.05). In contrast, the maximal killing of gentamicin was attenuated against one E. coli isolate and both P. aeruginosa isolates during co-culture with E. faecalis (P\u200a&amp;lt;\u200a0.05). The potency of gentamicin was variable against the three aforementioned isolates. Against the E. coli isolate, the potency of gentamicin was significantly reduced by the presence of either E. faecalis isolate (EC50 95% CI\u200a=\u200a4.23\u20134.43\u2009mg\/L monoculture versus 3.86\u20134.19\u2009mg\/L and 3.55\u20133.96\u2009mg\/L during co-culture with AME-producing and AME-deficient E. faecalis, respectively). The potency of gentamicin increased or decreased for P. aeruginosa depending on which E. faecalis isolate was investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The AME-producing E. faecalis did not provide a consistent protective effect from aminoglycosides for the Gram-negative pathogens.<\/jats:p><\/jats:sec>","DOI":"10.1093\/jac\/dkab211","type":"journal-article","created":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T19:23:11Z","timestamp":1622661791000},"page":"2610-2614","source":"Crossref","is-referenced-by-count":10,"title":["Capability of<i>Enterococcus faecalis<\/i>to shield Gram-negative pathogens from aminoglycoside exposure"],"prefix":"10.1093","volume":"76","author":[{"given":"Tiffany A","family":"McMurtry","sequence":"first","affiliation":[{"name":"California Northstate University College of Pharmacy, Elk Grove, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayeh","family":"Barekat","sequence":"additional","affiliation":[{"name":"California Northstate University College of Pharmacy, Elk Grove, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fantasia","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"California Northstate University College of Pharmacy, Elk Grove, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parwinder","family":"Purewal","sequence":"additional","affiliation":[{"name":"California Northstate University College of Pharmacy, Elk Grove, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5396-911X","authenticated-orcid":false,"given":"Zackery P","family":"Bulman","sequence":"additional","affiliation":[{"name":"University of Illinois at Chicago College of Pharmacy, Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2570-7593","authenticated-orcid":false,"given":"Justin R","family":"Lenhard","sequence":"additional","affiliation":[{"name":"California Northstate University College of Pharmacy, Elk Grove, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,7,10]]},"reference":[{"key":"2021120106084962900_dkab211-B1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3389\/fmed.2019.00074","article-title":"Treatment of infections due to MDR Gram-Negative bacteria","volume":"6","author":"Bassetti","year":"2019","journal-title":"Front Med (Lausanne)"},{"key":"2021120106084962900_dkab211-B2"},{"key":"2021120106084962900_dkab211-B3","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3389\/fmicb.2013.00121","article-title":"Rise and dissemination of aminoglycoside resistance: the aac(6\u2032)-Ib paradigm","volume":"4","author":"Ramirez","year":"2013","journal-title":"Front Microbiol"},{"key":"2021120106084962900_dkab211-B4","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.drup.2010.08.003","article-title":"Aminoglycoside modifying enzymes","volume":"13","author":"Ramirez","year":"2010","journal-title":"Drug Resist Update"},{"key":"2021120106084962900_dkab211-B5","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1089\/mdr.2012.0125","article-title":"Characterization of aminoglycoside-modifying enzymes in enterobacteriaceae clinical strains and characterization of the plasmids implicated in their diffusion","volume":"19","author":"Mir\u00f3","year":"2013","journal-title":"Microb Drug Resist"},{"key":"2021120106084962900_dkab211-B6","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.jgar.2013.06.005","article-title":"Polymicrobial bloodstream infections: epidemiology and impact on mortality","volume":"1","author":"Pavlaki","year":"2013","journal-title":"J Glob Antimicrob Resist"},{"key":"2021120106084962900_dkab211-B7","doi-asserted-by":"crossref","first-page":"0012-2012","DOI":"10.1128\/microbiolspec.UTI-0012-2012","article-title":"Gram-positive uropathogens, polymicrobial urinary tract infection, and the emerging microbiota of the urinary tract","volume":"4","author":"Kline","year":"2016","journal-title":"Microbiol Spectrum"},{"key":"2021120106084962900_dkab211-B8","doi-asserted-by":"crossref","first-page":"00378-17","DOI":"10.1128\/IAI.00378-17","article-title":"Enterococcus faecalis Promotes Innate Immune Suppression and Polymicrobial Catheter-Associated Urinary Tract Infection","volume":"85","author":"Tien","year":"2017","journal-title":"Infect Immun"},{"key":"2021120106084962900_dkab211-B9","first-page":"651","article-title":"Basic studies on the pathogenicity of Enterococcus faecalis: polymicrobial infection with Enterococcus faecalis and Proteus mirabilis in experimental ascending pyelonephritis models","volume":"39","author":"Yamasaki","year":"1991","journal-title":"Chemotherapy"},{"key":"2021120106084962900_dkab211-B10","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1093\/jac\/dkz247","article-title":"Bacterial brothers in arms: cooperation of Staphylococcus aureus and Pseudomonas aeruginosa during antimicrobial exposure","volume":"74","author":"Lenhard","year":"2019","journal-title":"J Antimicrob Chemother"},{"key":"2021120106084962900_dkab211-B11","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/S0924-8579(03)00244-9","article-title":"The indirect pathogenicity of Stenotrophomonas maltophilia","volume":"22","author":"Kataoka","year":"2003","journal-title":"Int J Antimicrob Agents"},{"key":"2021120106084962900_dkab211-B12","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1093\/jac\/12.6.599","article-title":"In-vivo protection of group A \u03b2-haemolytic streptococci from penicillin by \u03b2-lactamase-producing Bacteroides species","volume":"12","author":"Brook","year":"1983","journal-title":"J Antimicrob Chemother"},{"key":"2021120106084962900_dkab211-B13","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1542\/peds.31.3.463","article-title":"Staphylococcal antagonism to penicillin-G therapy of hemolytic streptococcal pharyngeal infection. Effect of oxacillin","volume":"31","author":"Simon","year":"1963","journal-title":"Pediatrics"},{"key":"2021120106084962900_dkab211-B14","doi-asserted-by":"crossref","first-page":"3536","DOI":"10.1128\/AAC.48.9.3536-3542.2004","article-title":"\u03b2-lactamase-producing nontypeable Haemophilus influenzae fails to protect Streptococcus pneumoniae from amoxicillin during experimental acute otitis media","volume":"48","author":"Westman","year":"2004","journal-title":"Antimicrob Agents Chemother"},{"key":"2021120106084962900_dkab211-B15","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1093\/infdis\/160.2.337","article-title":"The role of \u03b2-lactamase in mixed infections in mice in relation to treatment with ampicillin","volume":"160","author":"Renneberg","year":"1989","journal-title":"J Infect Dis"},{"key":"2021120106084962900_dkab211-B16","doi-asserted-by":"crossref","first-page":"115080","DOI":"10.1016\/j.diagmicrobio.2020.115080","article-title":"A coup d'\u00e9tat by NDM-producing Klebsiella pneumoniae overthrows the major bacterial population during KPC-directed therapy","volume":"98","author":"Lenhard","year":"2020","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2021120106084962900_dkab211-B17","doi-asserted-by":"crossref","first-page":"3983","DOI":"10.1128\/AAC.02636-13","article-title":"Sheltering effect and indirect pathogenesis of carbapenem-resistant Acinetobacter baumannii in polymicrobial infection","volume":"58","author":"Liao","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"key":"2021120106084962900_dkab211-B18","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1128\/AAC.47.9.2897-2902.2003","article-title":"The aminoglycoside 6\u2032-N-acetyltransferase type Ib encoded by Tn1331 is evenly distributed within the cell's cytoplasm","volume":"47","author":"Dery","year":"2003","journal-title":"Antimicrob Agents Chemother"},{"key":"2021120106084962900_dkab211-B19","doi-asserted-by":"crossref","first-page":"e00533-20","DOI":"10.1128\/AAC.00533-20","article-title":"Unraveling the gentamicin drug product complexity reveals variation in microbiological activities and nephrotoxicity","volume":"64","author":"Bulman","year":"2020","journal-title":"Antimicrob Agents Chemother"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/76\/10\/2610\/41319691\/dkab211.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/76\/10\/2610\/41319691\/dkab211.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T13:27:01Z","timestamp":1672320421000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/76\/10\/2610\/6318623"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,10]]},"references-count":19,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,7,10]]},"published-print":{"date-parts":[[2021,9,15]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkab211","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,10,1]]},"published":{"date-parts":[[2021,7,10]]}}}