{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T19:51:43Z","timestamp":1791834703736,"version":"4.3.4"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":8,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Hacettepe University Scientific Research Projects Coordination Unit","award":["22017"],"award-info":[{"award-number":["22017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the clinical and microbiological factors associated with the failure of levofloxacin prophylaxis in high-risk haematology patients, with a particular focus on the attainment of the pharmacokinetic\/pharmacodynamic (PK\/PD) target.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This prospective case\u2013control study evaluated adult high-risk haematology patients receiving levofloxacin prophylaxis (750\u2005mg\/day) during neutropenia. Analyses were performed at the episode level. Individual levofloxacin exposure was described using a population PK model, with the PK\/PD target defined as fAUC0\u201324\/MIC \u226580. Surveillance cultures were used to characterize Gram-negative bacterial (GNB) colonization and resistance profiles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 120 neutropenic episodes were analysed. Profound neutropenia was independently associated with prophylaxis failure (OR: 4.17; 95% CI: 1.70\u201310.2; P\u200a=\u200a0.002], whereas achievement of fAUC\/MIC \u226580 was independently associated with a reduced risk of failure (OR: 0.12; 95% CI: 0.02\u20130.62; P\u200a=\u200a0.012). Receiver operating characteristic curve analysis identified fAUC\/MIC \u226548.46 as the Youden-optimal cutoff (sensitivity 86.0%, specificity 38.3%; Youden J\u200a=\u200a0.243). Achievement of this cutoff was also independently associated with a reduced risk of prophylaxis failure (OR: 0.26; 95% CI: 0.083\u20130.803; P\u200a=\u200a0.019). Target non-attainment was strongly associated with levofloxacin-resistant GNB colonization, indicating that PK\/PD failure was predominantly MIC driven.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Levofloxacin prophylaxis failure appears to reflect an interplay between host factors and inadequate PK\/PD target attainment, which was largely influenced by levofloxacin-resistant GNB colonization. The standard 750\u2005mg dose was insufficient in a significant proportion of patients, supporting the need for prophylaxis strategies that integrate PK\/PD targets and local resistance patterns.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag284","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T11:38:57Z","timestamp":1785843537000},"source":"Crossref","is-referenced-by-count":2,"title":["Determinants of levofloxacin prophylaxis failure in high-risk haematology patients: a prospective study integrating resistant colonization and pharmacokinetic\/pharmacodynamic target attainment"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6501-2614","authenticated-orcid":false,"given":"Cemre","family":"Bo\u015fnak","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Hacettepe University Faculty of Medicine , Ankara ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2676-4557","authenticated-orcid":false,"given":"G\u00f6khan","family":"Metan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Hacettepe University Faculty of Medicine , Ankara ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u0131nar","family":"Zarakolu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Hacettepe University Faculty of Medicine , Ankara ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elifcan Alada\u011f","family":"Karakulak","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hacettepe University Faculty of Medicine , Ankara ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asl\u0131","family":"P\u0131nar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Hacettepe University Faculty of Medicine , Ankara ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakan","family":"G\u00f6ker","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hacettepe University Faculty of Medicine , Ankara ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason A","family":"Roberts","sequence":"additional","affiliation":[{"name":"Frazer Institute, Faculty of Medicine, Health, and Behavioral Sciences, The University of Queensland , Brisbane, Queensland ,","place":["Australia"]},{"name":"Department of Intensive Care Medicine and Pharmacy, Royal Brisbane and Women\u2019s Hospital , Brisbane, Queensland ,","place":["Australia"]},{"name":"Herston Infectious Diseases Institute (HeIDI), Metro North Health , Brisbane ,","place":["Australia"]},{"name":"UR UM 103, University of Montpellier, Division of Anesthesia Critical Care and Emergency and Pain Medicine, Nimes University Hospital , Nimes ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3565-0292","authenticated-orcid":false,"given":"Maria Patricia","family":"Hernandez-Mitre","sequence":"additional","affiliation":[{"name":"Frazer Institute, Faculty of Medicine, Health, and Behavioral Sciences, The University of Queensland , Brisbane, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Akova","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Hacettepe University Faculty of Medicine , Ankara ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"2026081212592337400_dkag284-B1","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1080\/14787210.2025.2487149","article-title":"Febrile neutropenia management in high-risk neutropenic patients: a narrative review on antibiotic prophylaxis and empirical treatment","volume":"23","author":"Bosnak","year":"2025","journal-title":"Expert Rev Anti Infect Ther"},{"key":"2026081212592337400_dkag284-B2","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.jinf.2017.10.009","article-title":"Fluoroquinolone prophylaxis in haematological cancer patients with neutropenia: ECIL critical appraisal of previous guidelines","volume":"76","author":"Mikulska","year":"2018","journal-title":"J Infect"},{"key":"2026081212592337400_dkag284-B3","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1097\/QCO.0b013e32834cf054","article-title":"Fluoroquinolones, antimicrobial resistance and neutropenic cancer patients","volume":"24","author":"Bow","year":"2011","journal-title":"Curr Opin Infect Dis"},{"key":"2026081212592337400_dkag284-B4","doi-asserted-by":"publisher","first-page":"446","DOI":"10.3947\/ic.2022.0005","article-title":"Bacteremia in hematopoietic stem cell recipients receiving fluoroquinolone prophylaxis: incidence, resistance, and risk factors","volume":"54","author":"Eryilmaz-Eren","year":"2022","journal-title":"Infect Chemother"},{"key":"2026081212592337400_dkag284-B5","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1038\/sj.bmt.1704431","article-title":"Pharmacokinetics and effects on bowel and throat microflora of oral levofloxacin as antibacterial prophylaxis in neutropenic patients with haematological malignancies","volume":"33","author":"Timmers","year":"2004","journal-title":"Bone Marrow Transplant"},{"key":"2026081212592337400_dkag284-B6","volume-title":"Breakpoint Tables for Interpretation of MICs and Zone Diameters, Version 15.0. V\u00e4xj\u00f6","author":"European Committee on Antimicrobial Susceptibility Testing (EUCAST)","year":"2025"},{"key":"2026081212592337400_dkag284-B7","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1093\/jac\/45.6.881","article-title":"Detection of extended-spectrum beta-lactamases in members of the family enterobacteriaceae: comparison of the MAST DD test, the double disc and the Etest ESBL","volume":"45","author":"M'Zali","year":"2000","journal-title":"J Antimicrob Chemother"},{"key":"2026081212592337400_dkag284-B8","doi-asserted-by":"publisher","first-page":"101","DOI":"10.2165\/00003088-199732020-00002","article-title":"The clinical pharmacokinetics of levofloxacin","volume":"32","author":"Fish","year":"1997","journal-title":"Clin Pharmacokinet"},{"key":"2026081212592337400_dkag284-B9","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1093\/cid\/ciab404","article-title":"Colonization with fluoroquinolone-resistant enterobacterales decreases the effectiveness of fluoroquinolone prophylaxis in hematopoietic cell transplant recipients","volume":"73","author":"Satlin","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2026081212592337400_dkag284-B10","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1111\/ijn.12099","article-title":"Prognostic factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia: a systematic review and meta-analysis","volume":"19","author":"Lee","year":"2013","journal-title":"Int J Nurs Pract"},{"key":"2026081212592337400_dkag284-B11","doi-asserted-by":"publisher","first-page":"e306","DOI":"10.1200\/JOP.19.00344","article-title":"Prospective initiative to reduce mucosal barrier injuries and bloodstream infections in patients with hematologic malignancy receiving inpatient chemotherapy","volume":"16","author":"Reed","year":"2020","journal-title":"JCO Oncol Pract"},{"key":"2026081212592337400_dkag284-B12","doi-asserted-by":"publisher","first-page":"4377","DOI":"10.1007\/s00520-016-3277-0","article-title":"Relationship between severity and duration of chemotherapy-induced neutropenia and risk of infection among patients with nonmyeloid malignancies","volume":"24","author":"Li","year":"2016","journal-title":"Support Care Cancer"},{"key":"2026081212592337400_dkag284-B13","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1097\/INF.0000000000002641","article-title":"Association between depth of neutropenia and clinical outcomes in febrile pediatric cancer and\/or patients undergoing hematopoietic stem-cell transplantation","volume":"39","author":"Alali","year":"2020","journal-title":"Pediatr Infect Dis J"},{"key":"2026081212592337400_dkag284-B14","doi-asserted-by":"publisher","first-page":"853","DOI":"10.3390\/antibiotics13090853","article-title":"Artificial intelligence to close the gap between pharmacokinetic\/pharmacodynamic targets and clinical outcomes in critically ill patients: a narrative review on beta lactams","volume":"13","author":"Gon\u00e7alves Pereira","year":"2024","journal-title":"Antibiotics (Basel)"},{"key":"2026081212592337400_dkag284-B15","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1001\/jama.279.2.125","article-title":"Pharmacodynamics of levofloxacin: a new paradigm for early clinical trials","volume":"279","author":"Preston","year":"1998","journal-title":"JAMA"},{"key":"2026081212592337400_dkag284-B16","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1128\/AAC.42.5.1098","article-title":"Levofloxacin population pharmacokinetics and creation of a demographic model for prediction of individual drug clearance in patients with serious community-acquired infection","volume":"42","author":"Preston","year":"1998","journal-title":"Antimicrob Agents Chemother"},{"key":"2026081212592337400_dkag284-B17","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1086\/383320","article-title":"Relationship between fluoroquinolone area under the curve: minimum inhibitory concentration ratio and the probability of eradication of the infecting pathogen, in patients with nosocomial pneumonia","volume":"189","author":"Drusano","year":"2004","journal-title":"J Infect Dis"},{"key":"2026081212592337400_dkag284-B18","doi-asserted-by":"publisher","first-page":"8930","DOI":"10.1038\/s41598-022-12627-1","article-title":"Population pharmacokinetics and dose optimization of intravenous levofloxacin in hospitalized adult patients","volume":"12","author":"Setiawan","year":"2022","journal-title":"Sci Rep"},{"key":"2026081212592337400_dkag284-B19","doi-asserted-by":"publisher","first-page":"2010","DOI":"10.1128\/AAC.01131-09","article-title":"Treatment with fluoroquinolones or with \u03b2-lactam-\u03b2-lactamase inhibitor combinations is a risk factor for isolation of extended-spectrum-\u03b2-lactamase-producing Klebsiella species in hospitalized patients","volume":"54","author":"Wener","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"key":"2026081212592337400_dkag284-B20","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1186\/s12866-025-04111-3","article-title":"Risk factors and outcomes of antibiotic-resistant Klebsiella pneumoniae bloodstream infections in adult patients with acute leukemia","volume":"25","author":"Wu","year":"2025","journal-title":"BMC Microbiol"},{"key":"2026081212592337400_dkag284-B21","doi-asserted-by":"publisher","first-page":"2962","DOI":"10.1128\/AAC.01341-07","article-title":"Plasmid-mediated qnrB2 and carbapenemase gene bla(KPC-2) carried on the same plasmid in carbapenem-resistant ciprofloxacin-susceptible Enterobacter cloacae isolates","volume":"52","author":"Chmelnitsky","year":"2008","journal-title":"Antimicrob Agents Chemother"},{"key":"2026081212592337400_dkag284-B22","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.1017\/S0950268813002975","article-title":"The prevalence of carbapenemase genes and plasmid-mediated quinolone resistance determinants in carbapenem-resistant Enterobacteriaceae from five teaching hospitals in central China","volume":"142","author":"Hu","year":"2014","journal-title":"Epidemiol Infect"},{"key":"2026081212592337400_dkag284-B23","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1016\/j.ajic.2019.11.025","article-title":"Evaluation of patient risk factors for infection with carbapenem-resistant Enterobacteriaceae","volume":"48","author":"Predic","year":"2020","journal-title":"Am J Infect Control"},{"key":"2026081212592337400_dkag284-B24","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1111\/ejh.13670","article-title":"Clinical and microbiological impact of long-term discontinuation of fluoroquinolone prophylaxis in haematological patients with prolonged profound neutropenia","volume":"107","author":"Verlinden","year":"2021","journal-title":"Eur J Haematol"},{"key":"2026081212592337400_dkag284-B25","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1093\/cid\/ciab1000","article-title":"Cessation of ciprofloxacin prophylaxis in hemato-oncology patients","volume":"75","author":"Caldwell","year":"2022","journal-title":"Clin Infect Dis"},{"key":"2026081212592337400_dkag284-B26","doi-asserted-by":"publisher","first-page":"3289","DOI":"10.1093\/jac\/dkae360","article-title":"Impact of discontinuing routine fluoroquinolone prophylaxis in neutropenic allogeneic haematopoietic stem cell transplant recipients: an observational study","volume":"79","author":"Stern","year":"2024","journal-title":"J Antimicrob Chemother"},{"key":"2026081212592337400_dkag284-B27","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1182\/bloodadvances.2022008226","article-title":"Levofloxacin prophylaxis vs no prophylaxis in patients with neutropenia within an endemic country for carbapenem-resistant GNB","volume":"7","author":"Clerici","year":"2023","journal-title":"Blood Adv"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/81\/9\/dkag284\/70619808\/dkag284.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/81\/9\/dkag284\/70619808\/dkag284.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T16:59:31Z","timestamp":1786553971000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/doi\/10.1093\/jac\/dkag284\/8759765"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":27,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,8,4]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkag284","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,9]]},"published":{"date-parts":[[2026,8,4]]},"article-number":"dkag284"}}