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Bactericidal activity of simulated serum concentrations of bid regimens of 400 mg cefditoren and 2000/125 mg amoxicillin/clavunanic acid against ampicillin susceptible and resistant H. influenzae: an in vitro pharmacodynamic model

Abstract number: 1733_1557

Gonzalez N., Echeverria O., Torrico M., Sevillano D., Gimenez M., Alou L., Aguilar L., Coronel P., Prieto J.

Objective: To explore the serum bactericidal activity over 48 h of simulated serum concentrations obtained after bid regimens of 400 mg cefditoren (CDN) and 2000/125 mg amoxicillin/clavulanic acid (AMC) against ampicillin (AMP) susceptible and resistant H. influenzae.

Methods: Three strains were used: a) AMP-susceptible b-lactamase negative strain (AMP-S) with AMC and CDN MICs of 2 and 0.015mg/mL; b) b-lactamase negative AMP-resistant strain (BLNAR) with AMC and CDN MICs of 8 and 0.12mg/mL; and c) b-lactamase positive AMC-resistant strain (BLPACR) with AMC and CDN MICs of 8 and 0.06mg/mL. The changing free and total antibiotic concentrations were simulated over 48 h (4 doses) in a computerised model based on a two-compartment model described previously (J Antimicrob Chemother 2004;54:1148–51). Initial inocula was approx. 108 cfu/mL. Antibiotic concentrations and colony counts were determined (in triplicate) at 0, 1, 2, 3, 4, 6, 8, 10, 12, 24, 25, 26, 27, 28, 30, 32, 34, 36 and 48 h. Limit of detection was 50 cfu/mL.

Results: Mean differences between log10 cfu/mL initial inocula and log10 cfu/mL at 24 h and 48 h sampling times are shown in the Table.

Strain24 h48 h
CDNAMCCDNAMC
FreeTotalFreeTotalFreeTotalFreeTotal  
AMP S>6.3*>6.3**4.14.3>6.3*>6.3**4.34.9
BLNAR3.75.0**3.03.13.75.5**3.23.5
BLPACR4.5*>6.3**0.10.84.6*>6.3**0.81.1
*P < 0.001 free CDN vs. free AMC; **P < 0.001 total CDN vs. total AMC.

Conclusions: 400 mg CDN total drug serum concentrations profile exhibited at 24 and 48 h significantly higher initial inocula reduction than 2000/125 mg AMC against the three strains tested regardless the resistance phenotype. CDN free-drug concentrations exhibited also higher initial inocula reduction than AMC against the three strains, with statistically significant reductions against the BLPACR phenotype and even against the AMP-S phenotype.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Subject:
Location: ICC, Munich, Germany
Presentation type:
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