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<p><i>Enterococcus faecalis</i> is responsible for numerous serious infections, and treatment options often include ampicillin combined with an aminoglycoside or dual beta-lactam therapy with ampicillin and a third-generation cephalosporin. The mechanism of dual beta-lactam therapy relies on the saturation of penicillin-binding proteins (PBPs). Ceftobiprole exhibits high affinity binding to nearly all <i>E. faecalis</i> PBPs, thus suggesting its potential utility in the treatment of severe <i>E. faecalis</i> infections. The availability of therapeutic drug monitoring (TDM) for ampicillin and ceftobiprole has prompted the use of this drug combination in our hospital. Due to the time-dependent antimicrobial properties of these antibiotics, an infusion administration longer than indicated was chosen. From January to December 2020, twenty-one patients were admitted to our hospital for severe <i>E. faecalis</i> infections and were treated with this approach. We retrospectively analyzed their clinical characteristics and pharmacological data. Most patients achieved an aggressive PK/PD target (T &gt; 4–8 minimum inhibitory concentration, MIC) when this alternative drug combination regimen was used. Our analysis included the study of <i>E. faecalis</i> biofilm production, as well as the kinetics of bacterial killing of ceftobiprole alone or in combination with ampicillin. Time-kill experiments revealed strong bactericidal activity of ceftobiprole alone at concentrations four times higher than the MIC for some enterococcal strains. In cases where a bactericidal effect of ceftobiprole alone was not evident, synergism with ampicillin and bactericidal activity were demonstrated instead. The prolonged infusion of ceftobiprole, either alone or with ampicillin, emerges as a valuable option for the treatment of severe invasive <i>E. faecalis</i> infections.</p>

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Evaluation of ampicillin plus ceftobiprole combination therapy in treating Enterococcus faecalis infective endocarditis and bloodstream infection

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月28日

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  • Simone Giuliano,
  • Jacopo Angelini,
  • Floriana Campanile,
  • Paola Conti,
  • Sarah Flammini,
  • Alberto Pagotto,
  • Francesco Sbrana,
  • Luca Martini,
  • Denise D’Elia,
  • Mohd H. Abdul-Aziz,
  • Menino O. Cotta,
  • Jason A. Roberts,
  • Robert A. Bonomo,
  • Carlo Tascini

摘要

Enterococcus faecalis is responsible for numerous serious infections, and treatment options often include ampicillin combined with an aminoglycoside or dual beta-lactam therapy with ampicillin and a third-generation cephalosporin. The mechanism of dual beta-lactam therapy relies on the saturation of penicillin-binding proteins (PBPs). Ceftobiprole exhibits high affinity binding to nearly all E. faecalis PBPs, thus suggesting its potential utility in the treatment of severe E. faecalis infections. The availability of therapeutic drug monitoring (TDM) for ampicillin and ceftobiprole has prompted the use of this drug combination in our hospital. Due to the time-dependent antimicrobial properties of these antibiotics, an infusion administration longer than indicated was chosen. From January to December 2020, twenty-one patients were admitted to our hospital for severe E. faecalis infections and were treated with this approach. We retrospectively analyzed their clinical characteristics and pharmacological data. Most patients achieved an aggressive PK/PD target (T > 4–8 minimum inhibitory concentration, MIC) when this alternative drug combination regimen was used. Our analysis included the study of E. faecalis biofilm production, as well as the kinetics of bacterial killing of ceftobiprole alone or in combination with ampicillin. Time-kill experiments revealed strong bactericidal activity of ceftobiprole alone at concentrations four times higher than the MIC for some enterococcal strains. In cases where a bactericidal effect of ceftobiprole alone was not evident, synergism with ampicillin and bactericidal activity were demonstrated instead. The prolonged infusion of ceftobiprole, either alone or with ampicillin, emerges as a valuable option for the treatment of severe invasive E. faecalis infections.