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JAC Advance Access originally published online on September 6, 2002
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Journal of Antimicrobial Chemotherapy (2002) 50, 525-532
© 2002 The British Society for Antimicrobial Chemotherapy

Effect of protein binding on the in vitro activity and pharmacodynamics of faropenem

F. J. Boswell, J. P. Ashby, J. M. Andrews and R. Wise*

Department of Microbiology, City Hospital NHS Trust, Birmingham B18 7QH, UK

Received 29 November 2001; returned 22 April 2002; revised 5 June 2002; accepted 21 June 2002

The influence of protein binding upon different aspects of the in vitro activity of faropenem on recently isolated Staphylococcus aureus and respiratory pathogens was determined. The protein binding of faropenem was investigated in inactivated human serum and albumin by ultrafiltration. The effect of the presence of inactivated human serum and albumin on the in vitro activity of faropenem and amoxicillin was established and the influence of protein binding on the pharmacodynamic properties of faropenem and amoxicillin was compared. The protein binding of faropenem was 96% and 95% in pooled inactivated human serum and 99% and 98% in 45 mg/L human albumin, at 8 and 25 mg/L, respectively. The presence of inactivated human serum (20% and 70%) increased the mean faropenem MICs by two dilution steps and albumin increased the mean faropenem MICs by three dilution steps. The mean amoxicillin MICs were less affected than faropenem by the presence of either inactivated human serum or albumin. Faropenem and amoxicillin exhibited similar time-dependent kinetics. Faropenem was bacteriostatic on Moraxella catarrhalis, Haemophilus influenzae and group A streptococci, and bactericidal for Streptococcus pneumoniae (after 4 h with concentrations equivalent to 5 x and 10 x MIC) in Iso-Sensitest broth. In 70% inactivated human serum faropenem was slowly bactericidal against M. catarrhalis, H. influenzae (one strain) and S. pneumoniae (one strain) but not group A streptococci and the other S. pneumoniae strain. A significant inoculum effect was observed with all strains except S. pneumoniae. Both faropenem and amoxicillin appeared more active in 70% inactivated human serum than in Iso-Sensitest broth.

* Corresponding author. Tel: +44-121-507-4255; Fax: +44-121-551-7763; E-mail: r.wise{at}bham.ac.uk


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