{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:13:32Z","timestamp":1787616812065,"version":"build-2736575974"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Investigator Initiated Trial"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Delafloxacin is a dual-targeting fluoroquinolone against topoisomerase IV and DNA gyrase that could decrease resistance selection by diminishing the likelihood of multiple mutational events in both enzymes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine the activity of delafloxacin against invasive Streptococcus pneumoniae isolates resistant to levofloxacin (LEV-R), compare delafloxacin MICs for LEV-R isolates with those of susceptible strains, and analyse mutations in QRDRs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 130 S. pneumoniae isolates (2014\u201320) were studied. The isolates were distributed according to levofloxacin MICs: high-level LEV-R (n\u200a=\u200a46; MIC\u200a&amp;gt;\u200a32\u2005mg\/L), low-level LEV-R (n\u200a=\u200a36; MIC range 3\u201312\u2005mg\/L) and susceptible (LEV-S; n\u200a=\u200a48; MIC \u22642\u2005mg\/L). We considered delafloxacin-resistant to be MIC\u200a\u2265\u200a0.12\u2005mg\/L (EUCAST epidemiological cut-off). MICs were determined by gradient diffusion (control strain S. pneumoniae ATCC 49619). All isolates were subjected to PCR and sequencing of parC, parE, gyrA and gyrB genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All LEV-S isolates showed delafloxacin MICs of \u22640.008\u2005mg\/L, and did not show mutations in QRDRs. Isolates with levofloxacin MICs of 3\u201312\u2005mg\/L showed delafloxacin MICs of &amp;lt;0.12\u2005mg\/L, with 3 (8.3%) presenting mutations in gyrA, and 11 (30.6%) in parC previously related to resistance. Isolates with levofloxacin MICs of &amp;gt;32\u2005mg\/L showed two to four mutations in QRDRs and 11 (24%) were delafloxacin resistant, presenting at least two mutations in gyrAS81F\/L\/V\u200a+\u200aparCS79F; four accumulated three mutations, and two showed four mutations in QRDRs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Among LEV-R pneumococci, 71 (87%) were susceptible to delafloxacin, indicating that it maintains its activity despite the presence of mutations in gyrA\u200a+\u200aparC that lead to high-level resistance to levofloxacin.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkaf308","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T11:53:27Z","timestamp":1754567607000},"page":"2834-2843","source":"Crossref","is-referenced-by-count":2,"title":["Molecular characterization of fluoroquinolone resistance in 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Cl\u00ednica y Enfermedades Infecciosas, Hospital General, Universitario Gregorio Mara\u00f1\u00f3n , Madrid ,","place":["Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital Gregorio Mara\u00f1\u00f3n , Madrid ,","place":["Spain"]},{"name":"Medicine Department, School of Medicine, Universidad Complutense, Madrid ,","place":["Spain"]},{"name":"CIBER Enfermedades Respiratorias-CIBERES (CB06\/06\/0058) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Iglesias","sequence":"additional","affiliation":[{"name":"Medical Department, Menarini , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda Cl\u00ednica y Enfermedades Infecciosas, Hospital General, Universitario Gregorio Mara\u00f1\u00f3n , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"P\u00e9rez-Abeledo","sequence":"additional","affiliation":[{"name":"Unidad de Microbiolog\u00eda Cl\u00ednica, Laboratorio Regional de Salud P\u00fablica de la Comunidad de Madrid , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"Sanz","sequence":"additional","affiliation":[{"name":"Unidad de Microbiolog\u00eda Cl\u00ednica, Laboratorio Regional de Salud P\u00fablica de la Comunidad de Madrid , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"2025110512450691400_dkaf308-B1","doi-asserted-by":"publisher","first-page":"342","DOI":"10.3390\/antibiotics12020342","article-title":"Distribution of multidrug-resistant invasive serotypes of Streptococcus pneumoniae during the period 2007-2021 in Madrid, 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