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JAC Advance Access originally published online on November 1, 2006
Journal of Antimicrobial Chemotherapy 2007 59(1):144-147; doi:10.1093/jac/dkl433
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Pharmacodynamic activity of ertapenem versus penicillin-susceptible and penicillin-non-susceptible Streptococcus pneumoniae using an in vitro model

George G. Zhanel1,3,*, Sheldon Derkatch1, Nancy Laing1,3, Ayman M. Noreddin4 and Daryl J. Hoban1,2

1 Department of Medical Microbiology, Faculty of Medicine, University of Manitoba 820 Sherbrook Street, Winnipeg, R3A 1R9, Canada 2 Department of Clinical Microbiology, Health Sciences Centre Winnipeg, R3A 1R9, Canada 3 Department of Medicine, Health Sciences Centre Winnipeg, R3A 1R9, Canada 4 College of Pharmacy, University of Minnesota, Duluth MN 55812, USA

Received 8 June 2006; returned 25 July 2006; revised 4 September 2006; accepted 3 October 2006

*Correspondence address. Microbiology, Health Sciences Centre, MS673-820 Sherbrook Street, Winnipeg, Manitoba, R3A 1R9, Canada. Tel: +1-204-787-4902; Fax: +1-204-787-4699; E-mail: ggzhanel{at}pcs.mb.ca

Background: Ertapenem is a novel carbapenem with activity against both penicillin-susceptible (MIC ≤ 0.06 mg/L) and penicillin-non-susceptible (MIC ≥ 0.12 mg/L) Streptococcus pneumoniae. This study assessed the pharmacodynamic activity of ertapenem against penicillin-susceptible and penicillin-non-susceptible S. pneumoniae using an in vitro pharmacodynamic model.

Methods: Fifteen S. pneumoniae strains including 3 penicillin-susceptible and 12 penicillin-non-susceptible [4 penicillin-intermediate (MIC 0.12–1 mg/L) and 8 penicillin-resistant (MIC ≥ 2 mg/L); with different resistance phenotypes including erythromycin-resistant (MIC ≥ 1 mg/L), ciprofloxacin-resistant (MIC ≥ 4 mg/L) and doxycycline-resistant (MIC ≥8 mg/L)] were studied. The in vitro pharmacodynamic model was inoculated with 1 x 106 cfu/mL and ertapenem was dosed once daily at 0 and 24 h to simulate f (free) Cmax and t1/2 obtained after a standard 1 g intravenous once daily dose in healthy volunteers (fCmax 15 mg/L, t1/2 4 h). Sampling was performed for 48 h to assess viable growth.

Results: Ertapenem T > MIC ≥ 80% (ertapenem MICs ≤ 0.5 mg/L) resulted in bactericidal (≥3 log10 killing) activity at 12, 24 and 48 h with complete eradication of penicillin-susceptible and penicillin-non-susceptible S. pneumoniae from the model with no regrowth over the 48 h study period. Ertapenem T > MIC ≤ 63% (ertapenem MIC ≥ 1 mg/L) resulted in bactericidal activity at 12 h with regrowth at 24 and 48 h. The observed MICs for S. pneumoniae of ertapenem studied in the in vitro model did not change during the 48 h period, even for strains where regrowth occurred.

Conclusions: Ertapenem is bactericidal against both penicillin-susceptible and penicillin-non-susceptible S. pneumoniae (ertapenem MICs ≤ 0.5 mg/L) when simulating free drug after 1 g intravenous once daily dosing.

Keywords: resistance , pharmacokinetics , antimicrobials


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G. G. Zhanel, P. Baudry, V. Vashisht, N. Laing, A. M. Noreddin, and D. J. Hoban
Pharmacodynamic activity of ertapenem versus multidrug-resistant genotypically characterized extended-spectrum {beta}-lactamase-producing Escherichia coli using an in vitro model
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