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PK/PD

  • Clinical Pharmacokinetics of Fosfomycin after Continuous Infusion Compared with Intermittent Infusion: a Randomized Crossover Study in Healthy Volunteers
    Clinical Therapeutics
    Clinical Pharmacokinetics of Fosfomycin after Continuous Infusion Compared with Intermittent Infusion: a Randomized Crossover Study in Healthy Volunteers

    Continuous infusion (CON) of fosfomycin has been proposed as potentially advantageous in certain clinical scenarios. However, no clinical data on the pharmacokinetics (PK) of fosfomycin after CON are available to date. This study aimed to investigate the PK of fosfomycin after CON and compare it with intermittent infusion (INT) of fosfomycin. A randomized two-way crossover study including 8 healthy male volunteers was performed. Each...

    Valentin al Jalali, Peter Matzneller, Beatrix Wulkersdorfer, Scharon Chou, Soma Bahmany, Birgit C. P. Koch, Markus Zeitlinger
  • <em>In Vivo</em> Pharmacodynamic Target Assessment of Antofloxacin against <span class="named-content genus-species" id="named-content-1">Streptococcus pneumoniae</span> and <span class="named-content genus-species" id="named-content-2">Staphylococcus aureus</span> in a Neutropenic Murine Pneumonia Model
    Pharmacology
    In Vivo Pharmacodynamic Target Assessment of Antofloxacin against Streptococcus pneumoniae and Staphylococcus aureus in a Neutropenic Murine Pneumonia Model

    We determined in vivo efficacy and target PK/PD exposures of antofloxacin against Streptococcus pneumoniae and Staphylococcus aureus in the murine pneumonia model. The mean plasma free drug area under the concentration-time curve/MIC (fAUC/MIC) targets associated with stasis and 1-...

    Yu-Feng Zhou, Ping Liu, Shu-He Dai, Jian Sun, Ya-Hong Liu, Xiao-Ping Liao
  • Impact of Loading Dose of Caspofungin in Pharmacokinetic-Pharmacodynamic Target Attainment for Severe Candidiasis Infections in Patients in Intensive Care Units: the CASPOLOAD Study
    Pharmacology
    Impact of Loading Dose of Caspofungin in Pharmacokinetic-Pharmacodynamic Target Attainment for Severe Candidiasis Infections in Patients in Intensive Care Units: the CASPOLOAD Study

    This study evaluated the impact of a high loading dose of caspofungin (CAS) on the pharmacokinetics of CAS and the pharmacokinetic-pharmacodynamic (PK-PD) target attainment in patients in intensive care units (ICU). ICU patients requiring CAS treatment were prospectively included to receive a 140-mg loading dose of CAS. Plasma CAS concentrations (0, 2, 3, 5, 7, and 24 h postinfusion) were determined to develop a two-compartmental...

    Sébastien Bailly, Elodie Gautier-Veyret, Minh P. Lê, Lila Bouadma, Olivier Andremont, Mathilde Neuville, Bruno Mourvillier, Romain Sonneville, Eric Magalhaes, Jordane Lebut, Aguila Radjou, Roland Smonig, Michel Wolff, Laurent Massias, Claire Dupuis, Jean-François Timsit
  • Pharmacodynamics of the Novel Metallo-β-Lactamase Inhibitor ANT2681 in Combination with Meropenem for the Treatment of Infections Caused by NDM-Producing <em>Enterobacteriaceae</em>
    Pharmacology
    Pharmacodynamics of the Novel Metallo-β-Lactamase Inhibitor ANT2681 in Combination with Meropenem for the Treatment of Infections Caused by NDM-Producing Enterobacteriaceae

    Enterobacteriaceae that produce metallo-β-lactamases (MBLs) are an emerging threat to public health. The metallo-β-lactamase inhibitor (MBLi) ANT2681 inhibits the enzymatic activity of MBLs through interaction with the dinuclear zinc ion cluster present in the active site that is common to these enzymes. ANT2681 is being codeveloped, with meropenem as the partner β-lactam, as a novel combination therapy for infections caused by...

    Shampa Das, Adam Johnson, Laura McEntee, Nicola Farrington, Adam Kirby, Jennifer Unsworth, Ana Jimenez-Valverde, Ruwanthi Kolamunnage-Dona, Justine Bousquet, Laethitia Alibaud, Carole Sable, Magdalena Zalacain, Martin Everett, William Hope
  • Optimal Dose or Optimal Exposure? Consideration for Linezolid in Tuberculosis Treatment
    Letter to the Editor
    Optimal Dose or Optimal Exposure? Consideration for Linezolid in Tuberculosis Treatment
    Hannah Yejin Kim, Shashikant Srivastava, Hemanth Kumar AK, Ben J. Marais, Jan-Willem Alffenaar
  • Toward Harmonization of Voriconazole CLSI and EUCAST Breakpoints for <span class="named-content genus-species" id="named-content-1">Candida albicans</span> Using a Validated <em>In Vitro</em> Pharmacokinetic/Pharmacodynamic Model
    Editor's Pick Susceptibility
    Toward Harmonization of Voriconazole CLSI and EUCAST Breakpoints for Candida albicans Using a Validated In Vitro Pharmacokinetic/Pharmacodynamic Model

    CLSI and EUCAST susceptibility breakpoints for voriconazole and Candida albicans differ by one dilution (≤0.125 and ≤0.06 mg/liter, respectively) whereas the epidemiological cutoff values for EUCAST (ECOFF) and CLSI (ECV) are the same (0.03 mg/liter). We therefore determined the pharmacokinetic/pharmacodynamic (PK/PD) breakpoints of voriconazole against...

    Maria-Ioanna Beredaki, Panagiota-Christina Georgiou, Maria Siopi, Lamprini Kanioura, David Andes, Maiken Cavling Arendrup, Johan W. Mouton, Joseph Meletiadis
  • Oral Fosfomycin Efficacy with Variable Urinary Exposures following Single and Multiple Doses against <em>Enterobacterales</em>: the Importance of Heteroresistance for Growth Outcome
    Clinical Therapeutics
    Oral Fosfomycin Efficacy with Variable Urinary Exposures following Single and Multiple Doses against Enterobacterales: the Importance of Heteroresistance for Growth Outcome

    Oral fosfomycin trometamol is licensed as a single oral dose for the treatment of uncomplicated urinary tract infections, with activity against multidrug-resistant uropathogens. The impact of interindividual variability in urinary concentrations on antimicrobial efficacy, and any benefit of giving multiple doses, is uncertain.

    Iain J. Abbott, Elke van Gorp, Rixt A. Wijma, Joseph Meletiadis, Jason A. Roberts, Johan W. Mouton, Anton Y. Peleg
  • Kinetic Driver of Antibacterial Drugs against <em>Plasmodium falciparum</em> and Implications for Clinical Dosing
    Pharmacology
    Kinetic Driver of Antibacterial Drugs against Plasmodium falciparum and Implications for Clinical Dosing

    Antibacterial drugs are an important component of malaria therapy. We studied the interactions of clindamycin, tetracycline, chloramphenicol, and ciprofloxacin against Plasmodium falciparum under static and dynamic conditions. In microtiter plate assays (static conditions), and as expected, parasites displayed the delayed death response characteristic for apicoplast-...

    Emily Caton, Elizabeth Nenortas, Rahul P. Bakshi, Theresa A. Shapiro
  • Open Access
    <em>In Vivo</em> Pharmacodynamic Study of Cefiderocol, a Novel Parenteral Siderophore Cephalosporin, in Murine Thigh and Lung Infection Models
    Experimental Therapeutics
    In Vivo Pharmacodynamic Study of Cefiderocol, a Novel Parenteral Siderophore Cephalosporin, in Murine Thigh and Lung Infection Models

    The pharmacokinetic (PK) and pharmacodynamic (PD) parameters which correlated with the in vivo efficacy of cefiderocol were evaluated using neutropenic murine thigh and lung infection models in which the infections were caused by a variety of Gram-negative bacilli.

    Rio Nakamura, Tsukasa Ito-Horiyama, Miki Takemura, Shinsuke Toba, Shuhei Matsumoto, Tatsuya Ikehara, Masakatsu Tsuji, Takafumi Sato, Yoshinori Yamano
  • Comparative Performance of Urinary Biomarkers for Vancomycin-Induced Kidney Injury According to Timeline of Injury
    Pharmacology
    Comparative Performance of Urinary Biomarkers for Vancomycin-Induced Kidney Injury According to Timeline of Injury

    Urinary biomarkers are superior to serum creatinine for defining onset and extent of kidney injury. This study classifies the temporal predictive ability of biomarkers for vancomycin-induced kidney injury (VIKI) as defined by histopathologic damage.

    Gwendolyn M. Pais, Sean N. Avedissian, J. Nicholas O’Donnell, Nathaniel J. Rhodes, Thomas P. Lodise, Walter C. Prozialeck, Peter C. Lamar, Cameron Cluff, Anil Gulati, Julie C. Fitzgerald, Kevin J. Downes, Athena F. Zuppa, Marc H. Scheetz

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