Development of breakpoints of carbapenems for intraabdominal infections based on pharmacokinetics and pharmacodynamics in peritoneal fluid

Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy
Kazuro IkawaTaijiro Sueda

Abstract

This study aimed to develop breakpoints of carbapenems for intraabdominal infections, based on pharmacokinetics (PK) and pharmacodynamics (PD) at the target site. Imipenem, meropenem, and doripenem were each administered to 8-11 patients before abdominal surgery, and venous blood and peritoneal fluid samples were obtained. The drug concentrations in plasma and peritoneal fluid were determined and analyzed using population pharmacokinetic modeling. Using the pharmacokinetic model parameters, a Monte Carlo simulation was performed to estimate the probabilities of attaining the bacteriostatic and bactericidal targets (20% and 40% of the time above the minimum inhibitory concentration [MIC], respectively) in peritoneal fluid. The bacteriostatic and bactericidal breakpoints were defined as the highest MIC values at which the bacteriostatic and bactericidal probabilities in peritoneal fluid were 80% or more. The breakpoints for the minimum and maximum approved dosages of each drug were identical for imipenem, meropenem, and doripenem, and some of these values varied with dosing interval and infusion time. Site-specific PK-PD-based breakpoints are proposed here for the first time, and should help us to select appropriate carbapenem re...Continue Reading

References

May 10, 2007·Drugs·George G ZhanelJames A Karlowsky
Jun 22, 2007·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Kayo IkedaMasao Kobayashi
Mar 22, 2008·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Kayo IkedaTaijiro Sueda
Jul 16, 2008·Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy·Kazuro IkawaTaijiro Sueda

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Citations

Dec 8, 2010·Intensive Care Medicine·Jared L CrandonDavid P Nicolau
Jul 3, 2009·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Kazuro Ikawa
Jan 23, 2010·Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy·Kazuro IkawaMasao Kobayashi
Nov 28, 2012·Scandinavian Journal of Infectious Diseases·Kazuro IkawaTaijiro Sueda
Mar 5, 2015·Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy·Eduardo Asín-PrietoArantxazu Isla
Sep 18, 2014·The Journal of Antibiotics·David S GomezSilvia R C J Santos
May 14, 2016·Journal of Applied Microbiology·M DouraghiA Abdollahi

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