Pharmacodynamic profiling of doripenem, imipenem and meropenem against prevalent Gram-negative organisms in the Asia-Pacific region
Carbapenems are increasingly being utilised owing to the escalating prevalence of antimicrobial-resistant Gram-negative bacteria from community and hospital settings. In this study, pharmacodynamic profiles of doripenem, imipenem and meropenem were evaluated against Gram-negative bacteria isolated f...
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th-mahidol.326442018-10-19T12:37:40Z Pharmacodynamic profiling of doripenem, imipenem and meropenem against prevalent Gram-negative organisms in the Asia-Pacific region Pattarachai Kiratisin Rebecca A. Keel David P. Nicolau Mahidol University California Northstate College of Pharmacy Hartford Hospital Medicine Carbapenems are increasingly being utilised owing to the escalating prevalence of antimicrobial-resistant Gram-negative bacteria from community and hospital settings. In this study, pharmacodynamic profiles of doripenem, imipenem and meropenem were evaluated against Gram-negative bacteria isolated from hospitalised patients. MICs for carbapenems were determined for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii obtained from the COMPACT II programme conducted in the Asia-Pacific region. Monte Carlo simulations were undertaken to assess the pharmacodynamic profile of carbapenems against each of the pathogens. All carbapenem regimens achieved optimal exposures [cumulative fraction of response (CFR) ≥90%] against E. coli and K. pneumoniae. Against P. aeruginosa, doripenem achieved 81.3-95.3% CFR, imipenem achieved 55.2-77.9% CFR and meropenem achieved 71.9-91.3% CFR; only doripenem regimens of 4-h infusion of 1000 mg every 8 h (q8h) and 1-h and 4-h infusion of 2000 mg q8h and a meropenem regimen of 3-h infusion of 2000 mg q8h obtained optimal exposures; all carbapenem regimens showed slight (1-7%) improvement in CFRs in favour of isolates collected from ICU sources. Against A. baumannii, CFRs were much lower (25.9-46.7% CFR) and no carbapenem regimens achieved optimal exposure in or outside the ICU. Owing to the high potency of carbapenems against these Enterobacteriaceae populations, standard regimens are likely to perform well in the Asia-Pacific region. However, larger doses combined with prolonged infusions will be required to increase the CFR for these carbapenems against resistant non-fermenting Gram-negatives such as P. aeruginosa and A. baumannii that are prevalent in these countries. © 2012 Elsevier B.V. and the International Society of Chemotherapy. 2018-10-19T05:37:40Z 2018-10-19T05:37:40Z 2013-01-01 Article International Journal of Antimicrobial Agents. Vol.41, No.1 (2013), 47-51 10.1016/j.ijantimicag.2012.09.007 18727913 09248579 2-s2.0-84871642090 https://repository.li.mahidol.ac.th/handle/123456789/32644 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84871642090&origin=inward |
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Medicine Pattarachai Kiratisin Rebecca A. Keel David P. Nicolau Pharmacodynamic profiling of doripenem, imipenem and meropenem against prevalent Gram-negative organisms in the Asia-Pacific region |
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Carbapenems are increasingly being utilised owing to the escalating prevalence of antimicrobial-resistant Gram-negative bacteria from community and hospital settings. In this study, pharmacodynamic profiles of doripenem, imipenem and meropenem were evaluated against Gram-negative bacteria isolated from hospitalised patients. MICs for carbapenems were determined for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii obtained from the COMPACT II programme conducted in the Asia-Pacific region. Monte Carlo simulations were undertaken to assess the pharmacodynamic profile of carbapenems against each of the pathogens. All carbapenem regimens achieved optimal exposures [cumulative fraction of response (CFR) ≥90%] against E. coli and K. pneumoniae. Against P. aeruginosa, doripenem achieved 81.3-95.3% CFR, imipenem achieved 55.2-77.9% CFR and meropenem achieved 71.9-91.3% CFR; only doripenem regimens of 4-h infusion of 1000 mg every 8 h (q8h) and 1-h and 4-h infusion of 2000 mg q8h and a meropenem regimen of 3-h infusion of 2000 mg q8h obtained optimal exposures; all carbapenem regimens showed slight (1-7%) improvement in CFRs in favour of isolates collected from ICU sources. Against A. baumannii, CFRs were much lower (25.9-46.7% CFR) and no carbapenem regimens achieved optimal exposure in or outside the ICU. Owing to the high potency of carbapenems against these Enterobacteriaceae populations, standard regimens are likely to perform well in the Asia-Pacific region. However, larger doses combined with prolonged infusions will be required to increase the CFR for these carbapenems against resistant non-fermenting Gram-negatives such as P. aeruginosa and A. baumannii that are prevalent in these countries. © 2012 Elsevier B.V. and the International Society of Chemotherapy. |
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Mahidol University |
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Mahidol University Pattarachai Kiratisin Rebecca A. Keel David P. Nicolau |
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Article |
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Pattarachai Kiratisin Rebecca A. Keel David P. Nicolau |
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Pattarachai Kiratisin |
title |
Pharmacodynamic profiling of doripenem, imipenem and meropenem against prevalent Gram-negative organisms in the Asia-Pacific region |
title_short |
Pharmacodynamic profiling of doripenem, imipenem and meropenem against prevalent Gram-negative organisms in the Asia-Pacific region |
title_full |
Pharmacodynamic profiling of doripenem, imipenem and meropenem against prevalent Gram-negative organisms in the Asia-Pacific region |
title_fullStr |
Pharmacodynamic profiling of doripenem, imipenem and meropenem against prevalent Gram-negative organisms in the Asia-Pacific region |
title_full_unstemmed |
Pharmacodynamic profiling of doripenem, imipenem and meropenem against prevalent Gram-negative organisms in the Asia-Pacific region |
title_sort |
pharmacodynamic profiling of doripenem, imipenem and meropenem against prevalent gram-negative organisms in the asia-pacific region |
publishDate |
2018 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/32644 |
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1763492346337427456 |