{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T08:25:48Z","timestamp":1769847948830,"version":"3.49.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T00:00:00Z","timestamp":1575244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Children Cancer-free (KiKa) Foundation and the Go4Children Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Ciprofloxacin is used as antimicrobial prophylaxis in pediatric acute lymphoblastic leukemia (ALL) to decrease infections with gram-negative bacteria. However, there are no clear guidelines concerning prophylactic dose.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>To determine the pharmacokinetics and pharmacodynamics (PKPD) of ciprofloxacin prophylaxis in a pediatric ALL population. The effect of patient characteristics and antileukemic treatment on ciprofloxacin exposure, the area under the concentration time curve over minimal inhibitory concentration (AUC24\/MIC) ratios, and emergence of resistance were studied.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A total of 615 samples from 129 children (0\u201318 years) with ALL were collected in a multicenter prospective study. A population pharmacokinetic model was developed. Microbiological cultures were collected prior to and during prophylaxis. An AUC24\/MIC of \u2265125 was defined as target ratio.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A 1-compartment model with zero-order absorption and allometric scaling best described the data. No significant (P &amp;lt; .01) covariates remained after backward elimination and no effect of asparaginase or azoles were found. Ciprofloxacin AUC24 was 16.9 mg*h\/L in the prednisone prophase versus 29.3 mg*h\/L with concomitant chemotherapy. Overall, 100%, 81%, and 18% of patients at, respectively, MIC of 0.063, 0.125, and 0.25 mg\/L achieved AUC24\/MIC \u2265 125. In 13% of the patients, resistant bacteria were found during prophylactic treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Ciprofloxacin exposure shows an almost 2-fold change throughout the treatment of pediatric ALL. Depending on the appropriateness of 125 as target ratio, therapeutic drug monitoring or dose adjustments might be indicated for less susceptible bacteria starting from \u2265 0.125 mg\/L to prevent the emergence of resistance and reach required targets for efficacy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciz1163","type":"journal-article","created":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T18:23:57Z","timestamp":1575311037000},"page":"e281-e288","source":"Crossref","is-referenced-by-count":9,"title":["Population Pharmacokinetics and Pharmacodynamics of Ciprofloxacin Prophylaxis in Pediatric Acute Lymphoblastic Leukemia Patients"],"prefix":"10.1093","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4525-638X","authenticated-orcid":false,"given":"S D T","family":"Sassen","sequence":"first","affiliation":[{"name":"Department of Pediatric Oncology, Erasmus MC-Sophia Children\u2019s Hospital, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R A A","family":"Math\u00f4t","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Pieters","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V","family":"de Haas","sequence":"additional","affiliation":[{"name":"Dutch Childhood Oncology Group (DCOG), The Hague, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G J L","family":"Kaspers","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, The Netherlands"},{"name":"Department of Pediatric Oncology, Emma\u2019s Children Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"van den Bos","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, The Netherlands"},{"name":"Department of Pediatric Oncology, Emma Children\u2019s Hospital, Academic Medical Center, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W J E","family":"Tissing","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, The Netherlands"},{"name":"Department of Pediatric Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D M W W","family":"te Loo","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hemato-Oncology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M B","family":"Bierings","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, The Netherlands"},{"name":"Pediatric Blood and Marrow Transplantation Program, University Medical Center Utrecht\/Wilhelmina Children\u2019s Hospital, \u00a0The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"van Westreenen","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus MC\u2013Sophia Children\u2019s Hospital, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I M","family":"van der Sluis","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Erasmus MC-Sophia Children\u2019s Hospital, Rotterdam, The Netherlands"},{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, The 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