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Pharmacodynamic profile of ertapenem against Klebsiella pneumoniae and Escherichia coli in a murine thigh model.
Antimicrob Agents Chemother. 2005 Jan; 49(1):276-80.AA

Abstract

The pharmacodynamic profile of ertapenem was evaluated in a neutropenic mouse thigh infection model. Extended-spectrum beta-lactamase (ESBL)-positive and ESBL-negative clinical strains of Escherichia coli and Klebsiella pneumoniae were studied. MICs ranged from 0.0078 to 0.06 microg/ml with standard inoculum tests. Ertapenem doses were administered once to five times daily to achieve various exposures, reported as the percentage of the dosing interval that the concentration of free ertapenem was in excess of the MIC (%T>MIC(free)). Mean values for the static exposure and 80% maximally effective exposure (ED(80)) were 19% (range, 2 to 38%) and 33% (range, 13 to 65%) T>MIC(free), respectively. Differences in exposure requirements based on the presence of an ESBL resistance mechanism or bacterial species were not evident. In addition, experiments using a 100-fold higher inoculum did not decrease the magnitude of the reduction in bacterial density from baseline achieved compared to lower-inoculum studies. The pharmacodynamic parameter of %T>MIC(free) correlated well with bactericidal activity for all isolates, and the static and ED(80) exposures are consistent with those reported previously for carbapenems.

Authors+Show Affiliations

Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour St., Hartford, CT 06102, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15616306

Citation

Maglio, Dana, et al. "Pharmacodynamic Profile of Ertapenem Against Klebsiella Pneumoniae and Escherichia Coli in a Murine Thigh Model." Antimicrobial Agents and Chemotherapy, vol. 49, no. 1, 2005, pp. 276-80.
Maglio D, Banevicius MA, Sutherland C, et al. Pharmacodynamic profile of ertapenem against Klebsiella pneumoniae and Escherichia coli in a murine thigh model. Antimicrob Agents Chemother. 2005;49(1):276-80.
Maglio, D., Banevicius, M. A., Sutherland, C., Babalola, C., Nightingale, C. H., & Nicolau, D. P. (2005). Pharmacodynamic profile of ertapenem against Klebsiella pneumoniae and Escherichia coli in a murine thigh model. Antimicrobial Agents and Chemotherapy, 49(1), 276-80.
Maglio D, et al. Pharmacodynamic Profile of Ertapenem Against Klebsiella Pneumoniae and Escherichia Coli in a Murine Thigh Model. Antimicrob Agents Chemother. 2005;49(1):276-80. PubMed PMID: 15616306.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacodynamic profile of ertapenem against Klebsiella pneumoniae and Escherichia coli in a murine thigh model. AU - Maglio,Dana, AU - Banevicius,Mary Anne, AU - Sutherland,Christina, AU - Babalola,Chinedum, AU - Nightingale,Charles H, AU - Nicolau,David P, PY - 2004/12/24/pubmed PY - 2005/2/23/medline PY - 2004/12/24/entrez SP - 276 EP - 80 JF - Antimicrobial agents and chemotherapy JO - Antimicrob Agents Chemother VL - 49 IS - 1 N2 - The pharmacodynamic profile of ertapenem was evaluated in a neutropenic mouse thigh infection model. Extended-spectrum beta-lactamase (ESBL)-positive and ESBL-negative clinical strains of Escherichia coli and Klebsiella pneumoniae were studied. MICs ranged from 0.0078 to 0.06 microg/ml with standard inoculum tests. Ertapenem doses were administered once to five times daily to achieve various exposures, reported as the percentage of the dosing interval that the concentration of free ertapenem was in excess of the MIC (%T>MIC(free)). Mean values for the static exposure and 80% maximally effective exposure (ED(80)) were 19% (range, 2 to 38%) and 33% (range, 13 to 65%) T>MIC(free), respectively. Differences in exposure requirements based on the presence of an ESBL resistance mechanism or bacterial species were not evident. In addition, experiments using a 100-fold higher inoculum did not decrease the magnitude of the reduction in bacterial density from baseline achieved compared to lower-inoculum studies. The pharmacodynamic parameter of %T>MIC(free) correlated well with bactericidal activity for all isolates, and the static and ED(80) exposures are consistent with those reported previously for carbapenems. SN - 0066-4804 UR - https://www.unboundmedicine.com/medline/citation/15616306/Pharmacodynamic_profile_of_ertapenem_against_Klebsiella_pneumoniae_and_Escherichia_coli_in_a_murine_thigh_model_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=15616306 DB - PRIME DP - Unbound Medicine ER -