Are oral cefuroxime axetil, cefixime and cefditoren pivoxil adequate to treat uncomplicated acute pyelonephritis after switching from intravenous therapy? A pharmacokinetic/pharmacodynamic perspective.
OBJECTIVES
The goal of this study is to assess, by means of pharmacokinetic/pharmacodynamic (PK/PD) analysis using the Monte Carlo simulation, the adequacy of oral cephalosporins cefuroxime axetil, cefixime and cefditoren at different dosing regimens as switch therapy after intravenous cephalosporin treatment in uncomplicated acute pyelonephritis.


METHODS
The methodology included: (i) dosing regimen selection and acquisition of pharmacokinetic data; (ii) microbiological data acquisition; and (iii) Monte Carlo simulation to estimate the PTA (probability of PK/PD target attainment) and CFR (cumulative fraction of response), as indicators of treatment success.


RESULTS
At the current susceptibility breakpoints defined by EUCAST and CLSI for either cefuroxime axetil or cefixime, the probability of bactericidal target attainment is zero for the dosage regimens simulated. Considering the bactericidal target %fT>MIC>70%, the likelihood of the cefuroxime 500-mg q8h regimen or the cefixime 200-mg q12h regimen producing this exposure or achieving this target is only above 90% for organisms yielding MICs≤0.5mg/l and MICs≤0.25mg/l, respectively. Cefditoren pivoxil 400mg q12h provided probabilities of bactericidal target attainment of 80% or higher for MICs≤0.03mg/l, and ≤0.25mg/l if considering total instead of free drug concentrations.


CONCLUSIONS
The results of the PK/PD target attainment analysis reveal that the likelihood of treatment success based upon the current breakpoints proposed by either EUCAST or CLSI is low. Of the three cephalosporins, cefixime 400mg q12h prove to be the best option in oral APN treatment, although this regimen is currently off label.
['Rodríguez-Gascón|Alicia|A|', 'Aguirre-Quiñonero|Amaia|A|', 'Canut-Blasco|Andrés|A|']
D061605:Administration, Intravenous D000284:Administration, Oral D000900:Anti-Bacterial Agents D020682:Cefixime D002444:Cefuroxime D002511:Cephalosporins D006801:Humans D011704:Pyelonephritis
Cefuroxime Cefixime Cefditoren Acute pyelonephritis Pharmacokinetic/pharmacodynamics Monte Carlo simulation Cefixima Cefuroxima Farmacocinética y farmacodinámica Pielonefritis aguda Simulación de Montecarlo