دورية أكاديمية
أعرض في EDS

Pharmacodynamics of Flucloxacillin in a Neutropenic Murine Thigh Infection Model: A Piece of the Puzzle towards Evidence-Based Dosing.

التفاصيل البيبلوغرافية
العنوان: Pharmacodynamics of Flucloxacillin in a Neutropenic Murine Thigh Infection Model: A Piece of the Puzzle towards Evidence-Based Dosing.
المؤلفون: Roelofsen EE; Department of Hospital Pharmacy, Haaglanden Medisch Centrum, 2512 VA The Hague, The Netherlands.; Rotterdam Clinical Pharmacometrics Group, 3015 GD Rotterdam, The Netherlands., de Winter BCM; Rotterdam Clinical Pharmacometrics Group, 3015 GD Rotterdam, The Netherlands.; Department of Hospital Pharmacy, Erasmus MC University Medical Center, 3015 GD Rotterdam, The Netherlands.; CATOR, Center for Antimicrobial Optimized Treatment Rotterdam, 3015 GD Rotterdam, The Netherlands., van der Spek H; Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center, 3015 GD Rotterdam, The Netherlands., Snijders S; Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center, 3015 GD Rotterdam, The Netherlands., Koch BCP; Rotterdam Clinical Pharmacometrics Group, 3015 GD Rotterdam, The Netherlands.; Department of Hospital Pharmacy, Erasmus MC University Medical Center, 3015 GD Rotterdam, The Netherlands.; CATOR, Center for Antimicrobial Optimized Treatment Rotterdam, 3015 GD Rotterdam, The Netherlands., van den Berg S; CATOR, Center for Antimicrobial Optimized Treatment Rotterdam, 3015 GD Rotterdam, The Netherlands.; Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center, 3015 GD Rotterdam, The Netherlands., Muller AE; CATOR, Center for Antimicrobial Optimized Treatment Rotterdam, 3015 GD Rotterdam, The Netherlands.; Department of Medical Microbiology and Infectious Diseases, Erasmus MC University Medical Center, 3015 GD Rotterdam, The Netherlands.; Department of Medical Microbiology, Haaglanden Medisch Centrum, 2512 VA The Hague, The Netherlands.
المصدر: Antibiotics (Basel, Switzerland) [Antibiotics (Basel)] 2022 Aug 03; Vol. 11 (8). Date of Electronic Publication: 2022 Aug 03.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101637404 Publication Model: Electronic Cited Medium: Print ISSN: 2079-6382 (Print) Linking ISSN: 20796382 NLM ISO Abbreviation: Antibiotics (Basel) Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI AG, 2012-
مستخلص: For decades, flucloxacillin has been used to treat methicillin-susceptible Staphylococcus aureus (MSSA). Little is still known about its pharmacodynamics (PD). The present study aimed to determine the pharmacokinetic (PK)/PD index and the PD-index value minimally required for efficacy. MICs of 305 MSSA isolates were measured to determine the wild-type distribution. The PD of 8 S. aureus, 1 S. pyogenes, and 1 S. agalactiae isolates were evaluated in a neutropenic murine thigh infection model. Two S. aureus isolates were used in a dose-fractionation study and a dose−response analysis was performed additionally in the in vivo model. Data were analyzed with a population PK and sigmoid maximum effect model. The end of the wild-type distribution was 1 mg/L. The percentage of time the unbound concentration was above MIC (%fT > MIC) was best correlated with efficacy. For S. aureus, median %fT > 0.25 × MIC required for 1-log reduction was 15%. The value for S. pyogenes was 10%fT > MIC and for S. agalactiae 22%fT > 0.25xMIC for a 1-log reduction. The effect of flucloxacillin reached a 2-log reduction of S. aureus at 20%fT > 0.25xMIC and also for S. pyogenes and S. agalactiae, a reduction was reached. These data may serve to optimize dosing regimens currently used in humans.
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فهرسة مساهمة: Keywords: MIC-distribution; PD-target; PK/PD index; beta-lactam
تواريخ الأحداث: Date Created: 20220826 Latest Revision: 20230308
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9405042
DOI: 10.3390/antibiotics11081049
PMID: 36009918
قاعدة البيانات: MEDLINE
الوصف
تدمد:2079-6382
DOI:10.3390/antibiotics11081049