Vol.55 No.5 September 2007
Influence of human albumin on in vitro activity of oral beta-lactam antibiotics against Streptococcus pneumoniae
1)Division of Clinical Microbiology, Department of Clinical Pathology, Tenri Hospital, 200 Mishima, Tenri, Nara, Japan
2)Central Laboratory Technical Section 3, Falco Biosystems Ltd.
Abstract
We evaluated the influence of human albumin (HA) on the in vitro activity of 8 oral beta-lactam antibiotics against 59 recently isolated strains of Streptococcus pneumoniae.
MICs were determined by broth microdilution with Mueller-Hinton broth alone (MHB) or supplemented with 4 g/dL human albumin (MHB-alb).
The geometric mean of MICs obtained in MHB-alb of amoxicillin, faropenem (FRPM), cefcapene pivoxil, cefotiam hexetil, cefteram pivoxil (CFTM-PI), cefditoren pivoxil (CDTR-PI), and cefpodoxime proxetil were 0.22, 0.39, 0.54, 0.86, 0.91, 1.06, and 1.12 μg/mL. The MIC ratio (MIC obtained in MHB-alb/MIC obtained in MHB) of FRPM, CDTR-PI, and CFTM-PI were 6.9, 4.2, and 2.3, and those of other antibiotics less than 2.0. HA had a greater influence on the antibacterial activity of FRPM, CDTR-PI, and CFTM-PI.
Susceptibility ratios of S. pneumoniae for tested antibiotics were calculated using two types of breakpoint (BP) MIC satisfying 40% time above MIC for the dosing interval. BP1 was based on total concentrations of human blood and total concentrations were revised by the coefficient of human serum protein binding rate (FRPM: 0.5, CDTR-PI: 0.2, CFTM-PI: 0.5, other antibiotics: 1) in BP2.
Susceptibility ratios with all antibiotics using BP1 and MIC with HA were similar to those using BP2 and MIC without HA.
These findings suggest that in the presence of HA, MICs of FRPM, CDTR-PI, and CFTM-PI were markedly increased over those of other antibiotics. Protein binding should therefore be considered in PK/PD BP for beta-lactam antibiotics.
Key word
protein-binding, pharmacokinetics, pharmacodynamics
Received
March 13, 2007
Accepted
July 6, 2007
Jpn. J. Chemother. 55 (5): 368-373, 2007
