Cefiderocol pharmacokinetics during acute pulmonary exacerbations in hospitalized adult persons with cystic fibrosis.

IF 4.1 2区 医学 Q2 MICROBIOLOGY
Christina Koenig, Marguerite L Monogue, Ryan K Shields, Colleen M Sakon, Andrew J Fratoni, Hanna F Roenfanz, James D Finklea, James S Pope, David P Nicolau, Joseph L Kuti
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引用次数: 0

Abstract

Persons with CF (pwCF) present altered pharmacokinetics (PK) and are often infected with multidrug-resistant (MDR) bacteria. Herein, we describe the PK of cefiderocol, a siderophore cephalosporin with potent activity against MDR Gram-negative rods, in hospitalized adult pwCF with acute pulmonary exacerbation (APE). PwCF received ≥3 doses of 2 g cefiderocol (3 h infusion) with frequency determined according to their estimated glomerular filtration rate (eGFR). Blood sampling collected at steady state. Concentrations were fitted using the non-parametric adaptive grid algorithm in Pmetrics for R. Ten pwCF were enrolled; nine completed the study with six receiving 2 g q8 h and three 2 g q6 h. A two-compartment model best fitted the data. Mean (SD) PK parameters were clearance, 5.66 (1.28) L/h; volume of central compartment, 5.81 (3.52) L, and intercompartment transfer constants, k12, 4.29 (3.46) and k21, 2.25 (2.76) h-1. Protein binding was 48% (35-57). The 2 g q8 h regimen achieved a mean free time above the MIC (fT >MIC) of 99% (94-99), 90% (69-100), and 64% (41-81) at MICs of 4 (susceptible), 8 (intermediate), and 16 (resistant) mg/L, respectively, with AUC24h of 1,191 (781-1,496) mg/L*h. In pwCF with eGFR >120 mL/min, 2 g q6 h attained 100% fT >MIC up to 8 mg/L and 87% (83-92) at 16 mg/L, with AUC24h of 1,279 (1,054-1,590) mg/L*h. Among these nine pwCF with APE with normal or augmented renal clearance, cefiderocol using label prescribed dosing regimens according to eGFR was well tolerated and achieved optimal fT >MIC exposure for pathogens up to MICs of 8 mg/L and AUC24h estimates similar to previously reported estimates in non-CF patients.

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来源期刊
CiteScore
10.00
自引率
8.20%
发文量
762
审稿时长
3 months
期刊介绍: Antimicrobial Agents and Chemotherapy (AAC) features interdisciplinary studies that build our understanding of the underlying mechanisms and therapeutic applications of antimicrobial and antiparasitic agents and chemotherapy.
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