Pharmacodynamic profiling of intravenous antibiotics against prevalent Gram-negative organisms across the globe: The PASSPORT Program—Asia-Pacific Region

Roberts, Jason A., Kwa, Andrea, Montakantikul, Preecha, Gomersall, Charles, Kuti, Joseph L. and Nicolau, David P. (2011) Pharmacodynamic profiling of intravenous antibiotics against prevalent Gram-negative organisms across the globe: The PASSPORT Program—Asia-Pacific Region. International Journal of Antimicrobial Agents, 37 3: 225-229. doi:10.1016/j.ijantimicag.2010.10.024

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Author Roberts, Jason A.
Kwa, Andrea
Montakantikul, Preecha
Gomersall, Charles
Kuti, Joseph L.
Nicolau, David P.
Title Pharmacodynamic profiling of intravenous antibiotics against prevalent Gram-negative organisms across the globe: The PASSPORT Program—Asia-Pacific Region
Journal name International Journal of Antimicrobial Agents   Check publisher's open access policy
ISSN 0924-8579
1872-7913
Publication date 2011-03
Year available 2010
Sub-type Article (original research)
DOI 10.1016/j.ijantimicag.2010.10.024
Volume 37
Issue 3
Start page 225
End page 229
Total pages 5
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2012
Language eng
Formatted 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.
Keyword Doripenem
Imipenem
Meropenem
Carbapenem
Pharmacodynamics
Resistance
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 18 December 2010.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 22 Dec 2011, 16:18:58 EST by Sia Athanasas on behalf of Anaesthesiology and Critical Care - RBWH