Population Pharmacokinetic Assessment and Pharmacodynamic Implications of Pediatric Cefepime Dosing for Susceptible-Dose-Dependent Organisms.

نویسندگان

  • Kensuke Shoji
  • John S Bradley
  • Michael D Reed
  • John N van den Anker
  • Christine Domonoske
  • Edmund V Capparelli
چکیده

The Clinical and Laboratory Standards Institute (CLSI) revised cefepime (CFP) breakpoints forEnterobacteriaceaein 2014, and MICs of 4 and 8 μg/ml were reclassified as susceptible-dose dependent (SDD). Pediatric dosing to provide therapeutic concentrations against SDD organisms has not been defined. CFP pharmacokinetics (PK) data from published pediatric studies were analyzed. Population PK parameters were determined using NONMEM, and Monte Carlo simulation was performed to determine an appropriate CFP dosage regimen for SDD organisms in children. A total of 664 CFP plasma concentrations from 91 neonates, infants, and children were included in this analysis. The median patient age was 1.0 month (interquartile range [IQR], 0.2 to 11.2 months). Serum creatinine (SCR) and postmenstrual age (PMA) were covariates in the final PK model. Simulations indicated that CFP dosing at 50 mg/kg every 8 h (q8h) (as 0.5-h intravenous [i.v.] infusions) will maintain free-CFP concentrations in serum of >4 and 8 μg/ml for >60% of the dose interval in 87.1% and 68.6% of pediatric patients (age, ≥30 days), respectively, and extending the i.v. infusion duration to 3 h results in 92.3% of patients with free-CFP levels above 8 μg/ml for >60% of the dose interval. CFP clearance (CL) is significantly correlated with PMA and SCR. A dose of 50 mg/kg of CFP every 8 to 12 h does not achieve adequate serum exposure for older children with serious infections caused by Gram-negative bacilli with a MIC of 8 μg/ml. Prolonged i.v. infusions may be useful for this population.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Adequacy of high-dose cefepime regimen in febrile neutropenic patients with hematological malignancies.

While guidelines recommend empirical cefepime therapy in febrile neutropenia, the mortality benefit of cefepime has been controversial. In light of this, recent reports on pharmacokinetic changes for several antibiotics in febrile neutropenia and the consequent suboptimal exposure call for a pharmacokinetic/pharmacodynamic evaluation of current dosing. This study aimed to assess pharmacokinetic...

متن کامل

Clinical pharmacodynamics of cefepime in patients infected with Pseudomonas aeruginosa.

We evaluated cefepime exposures in patients infected with Pseudomonas aeruginosa to identify the pharmacodynamic relationship predictive of microbiological response. Patients with non-urinary tract P. aeruginosa infections and treated with cefepime were included. Free cefepime exposures were estimated by using a validated population pharmacokinetic model. P. aeruginosa MICs were determined by E...

متن کامل

Optimal sampling theory: An overview of its application to pharmacokinetic studies in infants and children.

Sick neonates, infants, and children often require drug therapy to ameliorate or cure disease. The success of drug therapy is directly dependent on administration of the optimal dose at the ideal dosing interval.1,2 Determination of the optimal dose and dosing interval for a therapeutic agent requires a fundamental understanding of the complex interplay between a drug’s pharmacokinetic and phar...

متن کامل

Dosing of antibiotics in obesity.

PURPOSE OF REVIEW Obesity is becoming a major burden on healthcare systems worldwide. The management of infections is problematic due to both an increased risk of morbidity and mortality, as well as a lack of information about dosing of antibiotics in the obese population. Recommendations in this patient group are severely lacking, so clinicians need to consider pharmacokinetic/pharmacodynamic ...

متن کامل

Application of Antimicrobial Pharmacodynamic Concepts into Clinical Practice: Focus on -Lactam Antibiotics Insights from the Society of Infectious Diseases Pharmacists

Thomas P. Lodise, Pharm.D., Ben M. Lomaestro, Pharm.D., and George L. Drusano, M.D. In recent years there have been tremendous strides in understanding the relationship between the pharmacodynamics of -lactams and microbiologic response. For -lactams, in vitro and animal studies suggest that the amount of time in which free or non–protein-bound antimicrobial concentration exceeds the minimum in...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Antimicrobial agents and chemotherapy

دوره 60 4  شماره 

صفحات  -

تاریخ انتشار 2016