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

Antimicrobial Agents and Chemotherapy
Kensuke ShojiE Capparelli

Abstract

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...Continue Reading

References

Jun 1, 1992·Antimicrobial Agents and Chemotherapy·R H BarbhaiyaK A Pittman
Aug 1, 1997·Antimicrobial Agents and Chemotherapy·M D ReedJ L Blumer
Feb 10, 1998·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·W A Craig
Apr 17, 2001·The Pediatric Infectious Disease Journal·J S Bradley, A Arrieta
Apr 17, 2001·The Pediatric Infectious Disease Journal·A C Arrieta, J S Bradley
Jun 12, 2003·The Pediatric Infectious Disease Journal·Mireya UrreaAntonio Palomeque
Dec 4, 2003·American Journal of Infection Control·Mireya UrreaRafael Jiménez
Mar 20, 2004·Nature Reviews. Microbiology·George L Drusano
Jun 28, 2005·Antimicrobial Agents and Chemotherapy·Edmund CapparelliFernando Moya
Feb 8, 2006·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·K GoethaertH Goossens
Apr 29, 2006·The Pediatric Infectious Disease Journal·Suzy Santana CavalcanteLoíse Britto Cavalcante
Oct 17, 2007·Antimicrobial Agents and Chemotherapy·Sunil V BhatDavid L Paterson
May 2, 2008·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·H DingX Shen
May 3, 2008·Journal of Clinical Pharmacy and Therapeutics·V Lima-RogelS Romano-Moreno
Jul 23, 2008·The Pediatric Infectious Disease Journal·John S BradleyEdmund V Capparelli
Nov 28, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Helen W BoucherJohn Bartlett
Dec 5, 2008·Expert Review of Anti-infective Therapy·Andrea EndimianiRobert A Bonomo
May 4, 2010·The Journal of Pediatrics·Elisabeth E AddersonJames M Hoffman
May 14, 2010·The New England Journal of Medicine·Anton Y Peleg, David C Hooper
Jan 18, 2012·Obesity Surgery·Barrie S RichPhilip S Barie
Oct 24, 2012·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Nan-Yao LeeWen-Chien Ko
Nov 2, 2012·The Annals of Pharmacotherapy·Mary Covington WalkerKalen B Manasco
Dec 22, 2012·British Journal of Community Nursing·Annette Dunne
Jun 14, 2013·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Pranita D TammaKaren C Carroll

❮ Previous
Next ❯

Citations

Feb 22, 2018·Antimicrobial Agents and Chemotherapy·Helgi PadariIrja Lutsar
Sep 1, 2018·The Pediatric Infectious Disease Journal·Zaccaria RicciBianca Goffredo
Nov 2, 2019·Journal of Clinical Microbiology·Lindsey E NielsenRomney Humphries
Oct 10, 2019·Expert Opinion on Drug Metabolism & Toxicology·Manon TauzinRobert Cohen
Jul 1, 2020·Antimicrobial Agents and Chemotherapy·Mohammad H Al-ShaerCharles A Peloquin
Aug 2, 2017·Future Microbiology·Nazario D Rivera-ChaparroRachel G Greenberg
Mar 7, 2020·Clinical Pharmacokinetics·Jiajun LiuMarc H Scheetz
Nov 30, 2019·American Journal of Perinatology·Danielle McDonald, Pooja Shah

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

CRISPR Screens in Drug Resistance

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on the application of CRISPR-Cas system in high-throughput genome-wide screens to identify genes that may confer drug resistance.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Related Papers

Antimicrobial Agents and Chemotherapy
Adriana TremouletAdministrative Core Committee of the Best Pharmaceuticals for Children Act-Pediatric Trials Network
© 2021 Meta ULC. All rights reserved