دورية أكاديمية
Population Pharmacokinetics and Pharmacodynamics of Ciprofloxacin Prophylaxis in Pediatric Acute Lymphoblastic Leukemia Patients
| العنوان: | Population Pharmacokinetics and Pharmacodynamics of Ciprofloxacin Prophylaxis in Pediatric Acute Lymphoblastic Leukemia Patients |
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| المؤلفون: | Sassen, S D T, Mathôt, R A A, Pieters, R, de Haas, V, Kaspers, G J L, van den Bos, C, Tissing, W J E, te Loo, D M W W, Bierings, M B, van Westreenen, M, van der Sluis, I M, Zwaan, C M |
| المساهمون: | Children Cancer-free (KiKa) Foundation and the Go4Children Foundation |
| المصدر: | Clinical Infectious Diseases ; volume 71, issue 8, page e281-e288 ; ISSN 1058-4838 1537-6591 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Infectious Diseases, Microbiology (medical) |
| الوصف: | Background 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. Aims 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. Methods A total of 615 samples from 129 children (0–18 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 ≥125 was defined as target ratio. Results A 1-compartment model with zero-order absorption and allometric scaling best described the data. No significant (P < .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 ≥ 125. In 13% of the patients, resistant bacteria were found during prophylactic treatment. Conclusion 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 ≥ 0.125 mg/L to prevent the emergence of resistance and reach required targets for efficacy. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/cid/ciz1163 |
| DOI: | 10.1093/cid/ciz1163/32924808/ciz1163.pdf |
| الإتاحة: | https://doi.org/10.1093/cid/ciz1163Test http://academic.oup.com/cid/article-pdf/71/8/e281/34138882/ciz1163.pdfTest |
| حقوق: | http://creativecommons.org/licenses/by-nc/4.0Test/ |
| رقم الانضمام: | edsbas.431541D9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/cid/ciz1163 |
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