{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T13:23:08Z","timestamp":1768742588888,"version":"3.49.0"},"reference-count":26,"publisher":"Microbiology Society","issue":"4","license":[{"start":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T00:00:00Z","timestamp":1651017600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014812","name":"Nordic Pharma","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014812","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,27]]},"abstract":"<jats:p>\n                  <jats:bold>Introduction.<\/jats:bold> Fosfomycin has retained activity against many multi-drug resistant (MDR) Gram-negatives, and may be useful against extended spectrum beta-lactamase (ESBL) producing and carbapenem-resistant Enterobacterales to improve clinical outcomes.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Hypothesis\/Gap Statement.<\/jats:bold> There are few data from the UK on the susceptibility of invasive Gram-negative isolates to fosfomycin, especially in the era of increasing use of oral fosfomycin for urinary tract infections (UTIs).<\/jats:p>\n               <jats:p>\n                  <jats:bold>Aim.<\/jats:bold> We evaluated fosfomycin susceptibility against 100 consecutive Gram-negative bloodstream isolates, both individually, and in combination with other mechanistically similar and differing antibiotics. The aim was to investigate the synergy between antibiotic combinations against several <jats:italic>E. coli, K. pneumoniae and P. aeruginosa<\/jats:italic> isolates with variable levels of resistance.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methodology.<\/jats:bold> Disc diffusion and MIC test strip methods applying revised EUCAST guidelines for Fosfomycin were used, followed by the MTS\u2122 \u2018cross synergy\u2019 method for \u2018resistant\u2019 isolates as defined below: (a) Fosfomycin resistant by MIC test strip; (b) MDR isolates defined as being resistant to \u22653 classes of antibiotics (based on routine sensitivity testing; beta lactams were considered as a single class), and\/or (c) AMP C or ESBL or carbapenemase producers (or carbapenem resistant). FIC Index (Fractional Inhibitory Concentration Index) calculations were used to interpret findings, whereby: FIC = (MICA combination A+B\/\u2009MIC agent A) + (MICB combination A+B\/\u2009MIC agent B). A result of \u22640.5 was taken to indicate \u2018synergy\u2019, &gt;0.5\u2009and \u22641.0\u2009to indicate \u2018additive\u2019 effect, &gt;1.0\u2009and \u22644.0\u2009to indicate \u2018indifference\u2019, and &gt;4.0\u2009to indicate \u2018antagonism\u2019.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results.<\/jats:bold> We found that 95\/100 isolates were susceptible to fosfomycin by MIC test strip, with 88\/100 isolates susceptible to fosfomycin by disc, based on EUCAST guideline breakpoints. A total of 30\/100 isolates (the more \u2018resistant\u2019 of the 100) were eligible for synergy testing according to our definitions (see <jats:italic>Methodology<\/jats:italic>), with the remaining 70 isolates not tested further. Seventeen out of 30 were MDR, 2\/30 were AMP C producers and 9\/30 were ESBL producers. Overall, 34\/300 (11\u200a%) of all combination tests showed synergy and 161\/300 (54\u200a%) were additive. Synergy was most commonly detected between fosfomycin and beta-lactam antibiotics, including piperacillin\/tazobactam (10\/30; 33\u200a%), ceftazidime\/avibactam (10\/30; 30\u200a%), and temocillin (8\/30; 27\u200a%). An additive effect was most commonly detected with aztreonam (25\/30; 83\u200a%) and meropenem (25\/30; 83\u200a%), but 100\u200a% indifference was found with tigecycline (30\/30). No antagonism was identified with any antibiotic combination.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusion.<\/jats:bold> Fosfomycin non-susceptibility by MIC test strip was unusual. Synergy was variable when combining fosfomycin with other antibiotics against the more \u2018resistant\u2019 isolates. Synergistic\/additive effects were detected for beta-lactam\/fosfomycin combinations in &gt;80\u200a% of all such combinations, suggesting beta-lactams may be the preferred partner for fosfomycin. Agents with a discordant site of action were more likely to result in indifference. Antagonism was not detected.<\/jats:p>","DOI":"10.1099\/jmm.0.001524","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T16:18:44Z","timestamp":1651076324000},"source":"Crossref","is-referenced-by-count":8,"title":["Evaluation of in vitro activity of fosfomycin, and synergy in combination, in Gram-negative bloodstream infection isolates in a UK teaching hospital"],"prefix":"10.1099","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5543-6555","authenticated-orcid":false,"given":"Joseph","family":"Suich","sequence":"first","affiliation":[{"name":"The University of York, York, UK"},{"name":"Hull York Medical School, York, UK"},{"name":"Hull University Teaching Hospitals NHS Trust, Hull, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damian","family":"Mawer","sequence":"additional","affiliation":[{"name":"York Teaching Hospital NHS Trust, York, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjan","family":"van der Woude","sequence":"additional","affiliation":[{"name":"The University of York, York, UK"},{"name":"Hull York Medical School, York, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debbie","family":"Wearmouth","sequence":"additional","affiliation":[{"name":"Hull University Teaching Hospitals NHS Trust, Hull, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillipa","family":"Burns","sequence":"additional","affiliation":[{"name":"Hull University Teaching Hospitals NHS Trust, Hull, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ton","family":"Smeets","sequence":"additional","affiliation":[{"name":"Nordic Pharma B. V., Baam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin","family":"Barlow","sequence":"additional","affiliation":[{"name":"The University of York, York, UK"},{"name":"Hull York Medical School, York, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-51711-x"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2007.121004"},{"key":"R3","article-title":"WHO | Antimicrobial resistance, WHO","year":"2020"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2014.12.002"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/j.sjbs.2014.08.002"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1186\/s13756-021-00983-y"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2019.01.004"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-021-06253-x"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01121-14"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0278-9"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30753-3"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02498-16"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00068-15"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00079-17"},{"key":"R15","article-title":"UK Standards for Microbiology Investigations, Introduction to the preliminary identification of medically important bacteria and fungi from culture, ID1 (2). 1-32","year":"2017"},{"key":"R16","article-title":"Breakpoint tables for interpretation of MICs and zone diameters. Version 8.0","year":"2018"},{"key":"R17","article-title":"Liofilchem MIC Test Strip, US PI - Version 3","year":"2021"},{"key":"R18","article-title":"Breakpoint tables for interpretation of MICs and zone diameters. Version 11.0","year":"2021"},{"key":"R19","article-title":"Liofilchem, MTS Synergy Applicator System, (US patent US9365886B2): A device for standardising the in-vitro synergy testing of two antibiotics through the method of crossing the gradient strips. (Liofilchem, 2012)","year":"2021"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.14260\/jemds\/2021\/92"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.4103\/jfmpc.jfmpc_970_19"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1089\/mdr.2014.0036"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1089\/mdr.2018.0234"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2021.106344"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10080967"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00846-21"}],"container-title":["Journal of Medical Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jmm\/10.1099\/jmm.0.001524?crawler=true&mimetype=application\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T19:35:57Z","timestamp":1702582557000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jmm\/10.1099\/jmm.0.001524"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,27]]},"references-count":26,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,4,27]]}},"URL":"https:\/\/doi.org\/10.1099\/jmm.0.001524","relation":{},"ISSN":["0022-2615","1473-5644"],"issn-type":[{"value":"0022-2615","type":"print"},{"value":"1473-5644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,27]]}}}