JAC Advance Access originally published online on November 24, 2004
Journal of Antimicrobial Chemotherapy 2004 54(6):1062-1066; doi:10.1093/jac/dkh484
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
JAC vol.54 no.6 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved
Pharmacodynamic studies of amoxicillin against Streptococcus pneumoniae: comparison of a new pharmacokinetically enhanced formulation (2000 mg twice daily) with standard dosage regimens
Antibiotic Research Unit, Department of Medical Sciences, Infectious Diseases and Clinical Bacteriology, Uppsala University, Sweden
* Correspondence address. Department of Infectious Diseases, University Hospital MAS, 20502 Malmö, Sweden. Tel: +46-40-331806; Fax: +46-40-336279; Email: inga.odenholt{at}inf.mas.lu.se
Objectives: To compare the pharmacodynamic effects of a pharmacokinetically enhanced formulation of amoxicillin 2000 mg twice daily, with amoxicillin 875 mg twice daily, 875 mg three times daily and 500 mg three times daily against Streptococcus pneumoniae with different susceptibility to amoxicillin in an in vitro kinetic model.
Methods: Strains of S. pneumoniae with amoxicillin MICs of 1, 2, 4 and 8 mg/L at an initial inoculum of approximately 105 cfu/mL were exposed to amoxicillin in an in vitro kinetic model simulating the human serum concentration–time profile of the pharmacokinetically enhanced formulation twice daily (Cmax 17 mg/L after 1.5 h). All isolates were also exposed to amoxicillin with concentration–time profiles correlating to the human dosage of 875 mg twice daily (Cmax 15 mg/L after 1 h), 875 mg three times daily and 500 mg (Cmax 8 mg/L after 1 h) three times daily with simulated half-life of 1 h. Repeated samples were taken regularly during 24 h and viable counts were carried out.
Results: Overall, the pharmacokinetically enhanced formulation was more effective at reducing bacterial counts than any of the other formulations evaluated. Eradication was achieved with the enhanced formulation for strains with a MIC of 
2 mg/L, however, regrowth occurred with the other dosing regimens. In the experiments with the strain with a MIC of 4 mg/L, the enhanced formulation kept the bacterial counts 102 cfu/mL for at least 14 out of 24 h tested. In contrast, none of the other formulations reduced the bacterial counts down to 102 cfu/mL at any point. None of the regimens was able to eradicate the strain with an MIC of 8 mg/L, even though an initial substantial kill was noted with the enhanced formulation after both doses. The least effective dosage regimen for all strains was 875 mg twice daily.
Keywords: PK/PD , antibiotics , in vitro kinetic models , S. pneumoniae
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  I. Odenholt, E. Lowdin, and O. Cars Pharmacodynamic Effects of Telavancin against Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Strains in the Presence of Human Albumin or Serum and in an In Vitro Kinetic Model Antimicrob. Agents Chemother., September 1, 2007; 51(9): 3311 - 3316. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Olofsson, L. L. Marcusson, P. Komp Lindgren, D. Hughes, and O. Cars Selection of ciprofloxacin resistance in Escherichia coli in an in vitro kinetic model: relation between drug exposure and mutant prevention concentration J. Antimicrob. Chemother., June 1, 2006; 57(6): 1116 - 1121. [Abstract] [Full Text] [PDF]
|
|