Evaluation of the adequacy of the antimicrobial therapy of invasive Haemophilus influenzae infections: A pharmacokinetic/pharmacodynamic perspective |
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Authors: | Maitane Ibar-Bariain Alicia Rodríguez-Gascón Arantxa Isla María Ángeles Solinís Andrés Canut-Blasco |
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Institution: | 1. Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray ikergunea, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, Vitoria-Gasteiz, Spain;2. Microbiology Service, Hospital Universitario de Álava (HUA), Instituto de Investigación Sanitaria de Álava (BIOARABA), Servicio Vasco de Salud-Osakidetza, C/Francisco Leandro de Viana s/n, Vitoria-Gasteiz, Spain |
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Abstract: | IntroductionIn Europe, non-typeable H. influenzae (NTHi) is the leading cause of invasive H. influenzae disease in adults and is associated with high mortality. The goal of this study was to determine whether current antimicrobial treatments for H. influenzae infection in Spain are suitable based on their probability of achieving pharmacokinetic/pharmacodynamic (PK/PD) targets.MethodsPharmacokinetic parameters for the antibiotics studied (amoxicillin, amoxicillin/clavulanic acid, ampicillin, cefotaxime, ceftriaxone, imipenem and ciprofloxacin) and susceptibility data for H. influenzae were obtained from literature. A Monte Carlo simulation was used to estimate the probability of target attainment (PTA), defined as the probability that at least a specific value of a PK/PD index is achieved at a certain MIC, and the cumulative fraction of response (CFR), defined as the expected population PTA for a specific drug dose and a specific microorganism population.ResultsRegardless of dosing regimen, all antibiotics yielded CFR values of 100% or nearly 100% for all strains, including BL+, BL? and BLNAR, except amoxicillin and ampicillin for BL+. Thus, if an infection is caused by BL+ strains, treatment with amoxicillin and ampicillin has a high probability of failure (CFR ≤ 8%). For standard doses of amoxicillin, amoxicillin/clavulanic acid and imipenem, PK/PD breakpoints were consistent with EUCAST clinical breakpoints. For the other antimicrobials, PK/PD breakpoints were higher than EUCAST clinical breakpoints.ConclusionsOur study confirms by PK/PD analysis that, with the antimicrobials used as empirical treatment of invasive H. influenzae disease, a high probability of therapeutic success can be expected. |
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Keywords: | Adults Pharmacokinetics/pharmacodynamics Monte Carlo simulation Antimicrobial therapy Adultos Farmacocinética/farmacodinamia Simulación de Monte Carlo Terapia antimicrobiana |
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