Influence of TEM-1 Beta-lactamase on the Pharmacodynamic Activity of Simulated Total Versus Free-drug Serum Concentrations of Cefditoren (400 Milligrams) Versus Amoxicillin-clavulanic Acid (2,000/125 Milligrams) Against Haemophilus Influenzae...

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 2007 Aug 1

PMID 17664320

Citations 4

Authors

M Torrico

L Aguilar

N Gonzalez

M J Gimenez

O Echeverria

F Cafini

D Sevillano

L Alou

P Coronel

J Prieto

Affiliations

Soon will be listed here.

Abstract

The aim of this study was to explore bactericidal activity of total and free serum simulated concentrations after the oral administration of cefditoren (400 mg, twice daily [bid]) versus the oral administration of amoxicillin-clavulanic acid extended release formulation (2,000/125 mg bid) against Haemophilus influenzae. A computerized pharmacodynamic simulation was performed, and colony counts and beta-lactamase activity were determined over 48 h. Three strains were used: ampicillin-susceptible, beta-lactamase-negative ampicillin-resistant (BLNAR) (also resistant to amoxicillin-clavulanic acid) and beta-lactamase-positive amoxicillin-clavulanic acid-resistant (BLPACR) strains, with cefditoren MICs of < or =0.12 microg/ml and amoxicillin-clavulanic acid MICs of 2, 8, and 8 microg/ml, respectively. Against the ampicillin-susceptible and BLNAR strains, bactericidal activity (> or =3 log(10) reduction) was obtained from 6 h on with either total and free cefditoren or amoxicillin-clavulanic acid. Against the BLPACR strain, free cefditoren showed bactericidal activity from 8 h on. In amoxicillin-clavulanic acid simulations the increase in colony counts from 4 h on occurred in parallel with the increase in beta-lactamase activity for the BLPACR strain. Since both BLNAR and BLPACR strains exhibited the same MIC, this was due to the significantly lower (P < or = 0.012) amoxicillin concentrations from 4 h on in simulations with beta-lactamase positive versus negative strains, thus decreasing the time above MIC (T>MIC). From a pharmacodynamic point of view, the theoretical amoxicillin T>MIC against strains with elevated ampicillin/amoxicillin-clavulanic acid MICs should be considered with caution since the presence of beta-lactamase inactivates the antibiotic, thus rendering inaccurate theoretical calculations. The experimental bactericidal activity of cefditoren is maintained over the dosing interval regardless of the presence of a mutation in the ftsI gene or beta-lactamase production.

Citing Articles

Comment on the article: In vivo Pharmacokinetics/Pharmacodynamics Profiles for Appropriate Doses of Cefditoren pivoxil against S. pneumoniae in Murine Lung-Infection Model.

Gimenez M, Aguilar L, Alou L, Sevillano D Pharm Res. 2024; 41(8):1595-1597.

PMID: 38997597 DOI: 10.1007/s11095-024-03729-8.

Revisiting cefditoren for the treatment of community-acquired infections caused by human-adapted respiratory pathogens in adults.

Gimenez M, Aguilar L, Granizo J Multidiscip Respir Med. 2018; 13:40.

PMID: 30410757 PMC: 6214181. DOI: 10.1186/s40248-018-0152-5.

Beta-lactam effects on mixed cultures of common respiratory isolates as an approach to treatment effects on nasopharyngeal bacterial population dynamics.

Sevillano D, Aguilar L, Alou L, Gimenez M, Gonzalez N, Torrico M PLoS One. 2008; 3(12):e3846.

PMID: 19052648 PMC: 2587697. DOI: 10.1371/journal.pone.0003846.

Urine bactericidal activity against Escherichia coli isolates exhibiting different resistance phenotypes/genotypes in an in vitro pharmacodynamic model simulating urine concentrations obtained after oral administration of a 400-milligram single dose....

Sevillano D, Aguilar L, Alou L, Gimenez M, Torrico M, Gonzalez N Antimicrob Agents Chemother. 2007; 52(3):1184-6.

PMID: 18160517 PMC: 2258530. DOI: 10.1128/AAC.01247-07.

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