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JAC Advance Access published online on October 15, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh463
© 2004 by The British Society for Antimicrobial Chemotherapy
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Received May 20, 2004
Revised September 6, 2004
Accepted September 14, 2004

Brief report

Bactericidal activity of amoxicillin against non-susceptible Streptococcus pneumoniae in an in vitro pharmacodynamic model simulating the concentrations obtained with the 2000/125 mg sustained-release co-amoxiclav formulation

David Sevillano 1, Almudena Calvo 1, María-José Giménez 1, Luis Alou 1, Lorenzo Aguilar 1, Eva Valero 1, Antonio Carcas 2, and José Prieto 1*

1 Microbiology Department, School of Medicine, Universidad Complutense, Madrid, Spain
2 Pharmacology Unit, Universidad Autónoma, Madrid, Spain

* To whom correspondence should be addressed. E-mail: jprieto{at}med.ucm.es.


  Abstract

Objectives: To investigate the bactericidal activity against Streptococcus pneumoniae of simulated amoxicillin serum concentrations obtained in humans after 2000/125 mg sustained-release (SR) and 875/125 mg co-amoxiclav administered twice and three times a day, respectively.

Methods: An in vitro computerized pharmacodynamic simulation was carried out and colony counts were determined over 24 h. Ten strains non-susceptible to amoxicillin (four of them exhibiting an MIC of 4 mg/L, five strains with an MIC of 8 mg/L and one strain with an MIC of 16 mg/L) were used.

Results: With amoxicillin 2000 mg, an initial inoculum reduction >99.99% was obtained for strains with an MIC of 4 mg/L, ≥99% for strains with an MIC of 8 mg/L and 70.6% for the strain with an MIC of 16 mg/L at 24 h sampling time. At this sampling time, no reduction of initial inocula was obtained with amoxicillin 875 mg/8 h for two of the four strains with an MIC of 4 mg/L, three of the five strains with an MIC of 8 mg/L or for the strain with an MIC of 16 mg/L.

Conclusions: The new co-amoxiclav 2000/125 mg SR formulation appears to offer advantages versus previous formulations with respect to bactericidal activity against current amoxicillin non-susceptible strains.

Keywords: {beta}-lactams; pneumococcal isolates; inocula decrease.
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