{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T06:20:42Z","timestamp":1788502842298,"version":"build-2803163510"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Pivmecillinam, the oral version of mecillinam, represents one of the major recommended and used antibiotics for empiric and targeted treatment of urinary tract infections in primary care in Denmark, Norway and Sweden. Mecillinam resistant mutants in Escherichia coli develop easily in vitro, but their fitness cost has been shown to be high.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We revisited the resistance and consumption data from the monitoring programmes in the three countries and compared pivmecillinam with ciprofloxacin from 2010 to 2020.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Mecillinam resistance rates in Escherichia coli remained around 6% in Denmark and Norway relative to a constant consumption in Norway of 1.6\u20131.8 DID (defined daily doses per 1000 inhabitants per day), and even increasing in Denmark from 1.6 to 2.3 DID. In Sweden resistance was significantly lower at 4% related to the lower consumption of 0.5 DID. For ciprofloxacin, resistance rates fluctuated around 6%\u201312%, highest in Sweden with the highest consumption (0.8\u20130.6 DID) and lowest in Denmark (0.55\u20130.35 DID) and Norway (0.7\u20130.3 DID), although consumption declined significantly in all three countries.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Pivmecillinam is an example of an antibiotic, which easily develops resistance in vitro, but apparently can be used broadly in primary care without increase in resistance rates.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac396","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T21:54:09Z","timestamp":1667426049000},"page":"289-295","source":"Crossref","is-referenced-by-count":22,"title":["Pivmecillinam, the paradigm of an antibiotic with low resistance rates in <i>Escherichia coli<\/i> urine isolates despite high consumption"],"prefix":"10.1093","volume":"78","author":[{"given":"Niels","family":"Frimodt-M\u00f8ller","sequence":"first","affiliation":[{"name":"Department of Clinical Microbiology, Rigshospitalet , DK2100, Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar Skov","family":"Simonsen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infection Control, University Hospital of North Norway, and Faculty of Health Sciences, UiT\u2014The Arctic University of Norway , Troms\u00f8 , Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders Rhod","family":"Larsen","sequence":"additional","affiliation":[{"name":"Department of Bacteria, Parasites and Fungi, Statens Serum Institut , Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Kahlmeter","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Central Hospital , V\u00e4xj\u00f6 , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,11,28]]},"reference":[{"key":"2023010801152431200_dkac396-B1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0732-8893(97)00216-2","article-title":"Emergence of ciprofloxacin resistance in Escherichia coli isolates after widespread use of fluoroquinolones","volume":"30","author":"Ena","year":"1998","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2023010801152431200_dkac396-B2","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1093\/jac\/47.4.502","article-title":"Correlation between increased consumption of fluoroquinolones in outpatients and resistance of Escherichia coli from urinary tract infections","volume":"47","author":"Cizman","year":"2001","journal-title":"J Antimicrob 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resistance","volume":"65","author":"Jensen","year":"2010","journal-title":"J Antimicrob Chemother"},{"key":"2023010801152431200_dkac396-B6","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1093\/jac\/dkx465","article-title":"Effect of general practice characteristics and antibiotic prescribing on Escherichia coli antibiotic non-susceptibility in the West Midlands region of England: a 4-year ecological study","volume":"73","author":"Ironmonger","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"2023010801152431200_dkac396-B7","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1089\/mdr.2017.0034","article-title":"Antibacterial susceptibilities of Escherichia coli from community-acquired urinary tract infections in the Faroe Islands, associations with antibacterial sales, and comparison with Iceland and Denmark","volume":"24","author":"Magnussen","year":"2018","journal-title":"Microb Drug Res"},{"key":"2023010801152431200_dkac396-B8","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1093\/jac\/dky031","article-title":"Association between use of different antibiotics and trimethoprim resistance: going beyond the obvious crude association","volume":"73","author":"Pouwels","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"2023010801152431200_dkac396-B9","article-title":"Bacteriology in uncomplicated urinary tract infections in Norwegian general practice from 2001-2015","volume":"1","author":"Bollestad","year":"2017","journal-title":"BJGP Open"},{"key":"2023010801152431200_dkac396-B10","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0218134","article-title":"Selection and co-selection of antibiotic resistances among Escherichia coli by antibiotic use in primary care: an ecological analysis","volume":"14","author":"Pouwels","year":"2019","journal-title":"PLoS ONE"},{"key":"2023010801152431200_dkac396-B11","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1089\/mdr.2021.0010","article-title":"Antimicrobial resistance trends of Escherichia coli isolates from outpatient and inpatient urinary infections over a 20-year period","volume":"28","author":"Milano","year":"2022","journal-title":"Microb Drug Resist"},{"issue":"Suppl 2","key":"2023010801152431200_dkac396-B12","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0924-8579(03)00229-2","article-title":"Prevalence and antimicrobial susceptibility of pathogens in uncomplicated cystitis in Europe. The ECO.SENS study","volume":"22","author":"Kahlmeter","year":"2003","journal-title":"Int J Antimicrob Agents"},{"key":"2023010801152431200_dkac396-B13","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/newbio236135a0","article-title":"6fl-amidinopenicillanic acids\u2014a new group of antibiotics","volume":"236","author":"Lund","year":"1972","journal-title":"Nat New Biol"},{"key":"2023010801152431200_dkac396-B14","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1007\/BF01641339","article-title":"Clinical evaluation of a novel 13-lactam antibiotic: pivmecillinam (FL 1039)","volume":"3","author":"Bentzen","year":"1975","journal-title":"Infection"},{"key":"2023010801152431200_dkac396-B15","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.1469-0691.2004.00737.x","article-title":"Urinary concentrations, and urine ex-vivo effect of mecillinam and sulphamethizole","volume":"10","author":"Kerrn","year":"2004","journal-title":"Clin Microbiol Infect"},{"key":"2023010801152431200_dkac396-B16","doi-asserted-by":"crossref","first-page":"627267","DOI":"10.3389\/fmicb.2020.627267","article-title":"Susceptibility of clinical Enterobacterales isolates with common and rare carbapenemases to mecillinam","volume":"11","author":"Fuchs","year":"2021","journal-title":"Front Microbiol"},{"key":"2023010801152431200_dkac396-B17","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1093\/jac\/dkt404","article-title":"Clinical and bacteriological effects of pivmecillinam for ESBL-producing Escherichia coli or Klebsiella pneumoniae in urinary tract infections","volume":"69","author":"Jans\u00e5ker","year":"2013","journal-title":"J Antimicrob Chemother"},{"key":"2023010801152431200_dkac396-B18","doi-asserted-by":"crossref","first-page":"2503","DOI":"10.1093\/jac\/dky230","article-title":"Clinical and bacteriological efficacy of pivmecillinam treatment for uncomplicated urinary tract infections caused by ESBL-producing Escherichia coli: a prospective, multicentre, observational cohort study","volume":"73","author":"Bollestad","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"2023010801152431200_dkac396-B19","doi-asserted-by":"crossref","first-page":"105851","DOI":"10.1016\/j.ijantimicag.2019.11.008","article-title":"The efficacy of mecillinam against clinical multidrug-resistant Escherichia coli in a murine urinary tract infection model","volume":"55","author":"Zykov","year":"2020","journal-title":"Int J Antimicrob Agents"},{"key":"2023010801152431200_dkac396-B20","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3390\/antibiotics8020057","article-title":"Pivmecillinam for uncomplicated lower urinary tract infections caused by Staphylococcus saprophyticus\u2014cumulative observational data from four recent clinical studies","volume":"8","author":"Jans\u00e5ker","year":"2019","journal-title":"Antibiotics (Basel)"},{"key":"2023010801152431200_dkac396-B21","author":"DANMAP"},{"key":"2023010801152431200_dkac396-B22","author":"NORM\/NORM-VET"},{"key":"2023010801152431200_dkac396-B23","author":"SWEDRES-SVARM"},{"key":"2023010801152431200_dkac396-B24","author":"EUCAST"},{"key":"2023010801152431200_dkac396-B25","author":"EARS-Net"},{"key":"2023010801152431200_dkac396-B26","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1006934","article-title":"The mecillinam resistome reveals a role for peptidoglycan endopeptidases in stimulating cell wall synthesis in Escherichia coli","volume":"13","author":"Lai","year":"2017","journal-title":"PLoS Genet"},{"key":"2023010801152431200_dkac396-B27","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1128\/AAC.04819-14","article-title":"Amdinocillin (mecillinam) resistance mutations in clinical isolates and laboratory-selected mutants of Escherichia coli","volume":"59","author":"Thulin","year":"2015","journal-title":"Antimicrob Agents 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