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Title: Pharmacodynamic profiling of intravenous antibiotics against prevalent Gram-negative organisms across the globe: The PASSPORT Program - Asia-Pacific Region
Authors: Jason A. Roberts
Andrea Kwa
Preecha Montakantikul
Charles Gomersall
Joseph L. Kuti
David P. Nicolau
University of Queensland
Singapore General Hospital
Mahidol University
Prince of Wales Hospital Hong Kong
Hartford Hospital
Keywords: Medicine
Issue Date: 1-Mar-2011
Citation: International Journal of Antimicrobial Agents. Vol.37, No.3 (2011), 225-229
Abstract: Due to escalating antimicrobial resistance amongst Gram-negative organisms, the choice of effective empirical antimicrobial regimens has become challenging. Monte Carlo simulations were conducted for conventional and prolonged infusion regimens of doripenem, imipenem and meropenem using pharmacokinetic data from adult patients with conserved renal function. Minimum inhibitory concentration data against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii were incorporated from the COMPACT surveillance programme in the Asia-Pacific region of the world. The cumulative fraction of response (CFR) was determined for each regimen against each bacterial population. All simulated carbapenem regimens achieved an optimal CFR against E. coli and K. pneumoniae (94.5-100% CFR). Against P. aeruginosa, doripenem achieved 78.7-92.6% CFR, imipenem achieved 60.4-79.0% CFR and meropenem achieved 73.0-85.1% CFR. The only dosing regimen to achieve ≥90% CFR against P. aeruginosa was doripenem 1000 mg and 2000 mg every 8 h (4-h infusion). Carbapenem CFRs against A. baumannii were much lower (29.2-54.4% CFR). CFRs for non-fermenting isolates were ca. 10% lower for isolates collected in the Intensive Care Unit. Carbapenem resistance amongst Enterobacteriaceae remains low in the Asia-Pacific region and thus standard carbapenem dosing regimens had a high likelihood of achieving pharmacodynamic exposures. However, larger doses combined with prolonged infusion will be required to increase the CFR for these carbapenems against resistant non-fermenting Gram-negatives that are common in these countries. The safety and efficacy of these high dosing regimens will need to be confirmed in the clinical setting. © 2010 Elsevier B.V. and the International Society of Chemotherapy.
ISSN: 09248579
Appears in Collections:Scopus 2011-2015

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