{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:00:30Z","timestamp":1778641230182,"version":"3.51.4"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Health and Medical Research Council Practitioner Fellowships","award":["APP1117940"],"award-info":[{"award-number":["APP1117940"]}]},{"name":"National Health and Medical Research Council Practitioner Fellowships","award":["APP1117065"],"award-info":[{"award-number":["APP1117065"]}]},{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"crossref","award":["APP1099452"],"award-info":[{"award-number":["APP1099452"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>The use of oral fosfomycin for urinary tract infections (UTIs) caused by non-Escherichia coli uropathogens is uncertain, including Klebsiella pneumoniae, the second most common uropathogen.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A multicompartment bladder infection in vitro model was used with standard media and synthetic human urine (SHU) to simulate urinary fosfomycin exposure after a single 3\u2005g oral dose (fAUC0\u201372 16884\u2005mg\u00b7h\/L, t\u00bd 5.5\u2005h) against 15 K. pneumoniae isolates including ATCC 13883 (MIC 2 to &amp;gt;1024\u2005mg\/L) with a constant media inflow (20\u2005mL\/h) and 4-hourly voiding of each bladder. The impact of the media (CAMHB + G6P versus SHU) on fosfomycin MIC measurements, drug-free growth kinetics and regrowth after fosfomycin administration was assessed. A low and high starting inoculum (5.5 versus 7.5 log10 cfu\/mL) was assessed in the bladder infection model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Compared with CAMHB, isolates in SHU had a slower growth rate doubling time (37.7 versus 24.1\u2005min) and reduced growth capacity (9.0 \u00b1 0.3 versus 9.4 \u00b1 0.3\u2005log10 cfu\/mL), which was further restricted with increased inflow rate (40\u2005mL\/h) and more frequent voids (2-hourly). Regrowth was commonly observed in both media with emergence of fosfomycin resistance promoted by a high starting inoculum in CAMHB (MIC rise to \u22651024\u2005mg\/L in 13\/14 isolates). Resistance was rarely detected in SHU, even with a high starting inoculum (MIC rise to \u22651024\u2005mg\/L in 2\/14 isolates).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Simulated in an in vitro UTI model, the regrowth of K. pneumoniae urinary isolates was inadequately suppressed following oral fosfomycin therapy. Efficacy was further reduced by a high starting inoculum.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac045","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T12:07:57Z","timestamp":1644322077000},"page":"1324-1333","source":"Crossref","is-referenced-by-count":16,"title":["Oral fosfomycin activity against <i>Klebsiella pneumoniae<\/i> in a dynamic bladder infection <i>in vitro<\/i> model"],"prefix":"10.1093","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6590-6127","authenticated-orcid":false,"given":"Iain J.","family":"Abbott","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elke","family":"van Gorp","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Alfred Hospital and Central Clinical School, 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