Pharmacodynamics of Imipenem in Critically Ill Patients
with Ventilator-Associated Pneumonia
Sutep Jaruratanasirikul MD*, Nanchanit Aeinlang MPharm*,
Monchana Jullangkoon MPharm*, Wibul Wongpoowarak MPharm**
Affiliation :
* Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
** Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences,
Prince of Songkla University, Hat Yai, Songkhla, Thailand
Background : Drug dispositions are altered in critically ill patients, including ventilator-associated pneumonia (VAP) when
compared with healthy subjects leading to fluctuations of plasma concentrations.
Objective : To compare the probability of target attainment (PTA) and cumulative fraction of response (CFR) for imipenem
between administration by 0.5-hour and 2-hour infusions.
Material and Method: The present study was a randomized three-way crossover in nine patients with VAP. Each patient
received imipenem in three regimens consecutively: (i) a 0.5-hour infusion of 0.5 g every six hours for 24 hours; (ii) a 2-hour
infusion of 0.5 g every six hours for 24 hours; and (iii) a 2-hour infusion of 1 g every six hours for 24 hours. Monte Carlo
simulation was performed to determine the PTA at various regimens and the study used susceptibility patterns obtained
from EUCAST and MYSTIC for assessment of CFR.
Results : For an MIC of 2 μg/ml, the PTAs achieving 40% T>MIC following a 0.5-hour infusion of 0.5 g, a 2-hour infusion
of 0.5 g, and a 2-hour infusion of 1 g were 90.93%, 98.97%, and 100%, respectively. Only a 2-hour infusion of 1 g achieved
98.75% of the PTA of 40% T>MIC for an MIC of 4 μg/ml. All regimens were predicted to achieve CFR >99% against E.
coli and Klebsiella spp.
Conclusion : A 2-hour infusion of 1 g regimen was predicted to have the highest PTA rates. All regimens achieved a high
CFR against E. coli and Klebsiella spp.
Keywords : Pharmacokinetics/pharmacodynamics, Pharmacodynamics, Population pharmacokinetics, Imipenem,
Carbapenems, Ventilator-associated pneumonia
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