The relationship between pharmacokinetics and pharmacodynamics is a key instrument to improve antimicrobial stewardship and should be aimed to identification of the drug exposure measure that is closely associated not...The relationship between pharmacokinetics and pharmacodynamics is a key instrument to improve antimicrobial stewardship and should be aimed to identification of the drug exposure measure that is closely associated not only with the ability to kill organisms but also to suppress the emergence of resistant subpopulations. This article reviews published studies for efficacy prediction with cefditoren and those aimed to explore its potential for countering resistance spread, focusing on the three most prevalent community-acquired isolates from respiratory infections: Streptococcus pneumoniae(S. pneumoniae), Haemophilus influenzae(H. influenzae) and Streptococcus pyogenes(S. pyogenes). Studies for efficacy prediction include in vitro pharmacodynamic simulations(using physiological concentrations of human albumin) and mice models(taking advantage of the same protein binding rate in mice and humans) to determine the value of the pharmacodynamic indices predicting efficacy, and Monte Carlo simulations to explore population pharmacodynamic coverage, as weapons for establishing breakpoints. Studies exploring the potential of cefditoren(free concentrations obtained with 400 mg cefditoren bid administration) for countering spread of resistance showed itscapability for countering(1) intra-strain spread of resistance linked to fts I gene mutations in H. influenzae;(2) the spread of H. influenzae resistant strains(with fts I gene mutations) in multi-strain H. influenzae niches or of S. pneumoniae strains with multiple resistance traits in multi-strain S. pneumoniae niches; and(3) for overcoming indirect pathogenicity linked to β-lactamase production by H. influenzae that protects S. pyogenes in multibacterial niches. This revision evidences the ecological potential for cefditoren(countering resistance spread among human-adapted commensals) and its adequate pharmacodynamic coverage of respiratory pathogens(including those resistant to previous oral compounds) producing community-acquired infections.展开更多
文摘The relationship between pharmacokinetics and pharmacodynamics is a key instrument to improve antimicrobial stewardship and should be aimed to identification of the drug exposure measure that is closely associated not only with the ability to kill organisms but also to suppress the emergence of resistant subpopulations. This article reviews published studies for efficacy prediction with cefditoren and those aimed to explore its potential for countering resistance spread, focusing on the three most prevalent community-acquired isolates from respiratory infections: Streptococcus pneumoniae(S. pneumoniae), Haemophilus influenzae(H. influenzae) and Streptococcus pyogenes(S. pyogenes). Studies for efficacy prediction include in vitro pharmacodynamic simulations(using physiological concentrations of human albumin) and mice models(taking advantage of the same protein binding rate in mice and humans) to determine the value of the pharmacodynamic indices predicting efficacy, and Monte Carlo simulations to explore population pharmacodynamic coverage, as weapons for establishing breakpoints. Studies exploring the potential of cefditoren(free concentrations obtained with 400 mg cefditoren bid administration) for countering spread of resistance showed itscapability for countering(1) intra-strain spread of resistance linked to fts I gene mutations in H. influenzae;(2) the spread of H. influenzae resistant strains(with fts I gene mutations) in multi-strain H. influenzae niches or of S. pneumoniae strains with multiple resistance traits in multi-strain S. pneumoniae niches; and(3) for overcoming indirect pathogenicity linked to β-lactamase production by H. influenzae that protects S. pyogenes in multibacterial niches. This revision evidences the ecological potential for cefditoren(countering resistance spread among human-adapted commensals) and its adequate pharmacodynamic coverage of respiratory pathogens(including those resistant to previous oral compounds) producing community-acquired infections.
