Show Notes
Communicable is launching a new series on everything related to pharmacokinetics (PK) and pharmacodynamics (PD). Kicking off this series are hosts Thomas Tängdén, Erin McCreary and Angela Huttner, and invited guests Amy Legg and Rekha Pai Mangalore. They walk us through key parameters and terms of PK/PD, such as volume of distribution, minimum inhibitory concentration (MIC), epidemiological cut-off value (ECOFF), and PK/PD indices, laying the foundation to better comprehend clinical applications such as setting a clinical breakpoint and how it guides therapeutic drug monitoring (TDM). This first episode encompasses a broad scope across PK/PD theory, preparing the listener for subsequent episodes that will explore these topics with greater depth and make you love PK/PD. This episode was peer-reviewed by Ummu Afeera Zainulabid of the International Islamic University, Kuantan, Malaysia. Terms and definitions ADME, a drug’s journey through the body: absorption, distribution, metabolism, excretion Volume of distribution, a parameter describing the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma Clearance, the volume of blood cleared of drug per unit time Half-life, the time required for the concentration of a drug to decrease to half of its initial amount in the body Loading dose, a larger initial dose designed to rapidly bring drug levels into the therapeutic range Steady state, an equilibrial condition in which the rate of input of a drug is equal to the rate of its output MIC, minimum inhibitory concentration ECOFF, epidemiological cut-off value: the highest MIC value of isolates that are not known to have resistance and are therefore considered representative of wild-type bacterial isolates Clinical breakpoint setting, takes into account drug dosing, PK/PD, site of infection, clinical data; what we think is the breakpoint for the lab to call a bacterial organism susceptible to a drug PK/PD index, a parameter that describes the observed antimicrobial activity of an antimicrobial; there are three different indices: T>MIC (bacterial killing depends on the drug concentration’s remaining higher than the MIC over time) Cmax/MIC (bacterial killing depends on the drug’s peak concentration) AUC/MIC (bacterial killing depends on the area under the curve over the MIC)
TDM, therapeutic drug monitoring Further reading Mouton JW, et al. MIC-based dose adjustment: facts and fables. J Antimicrob Chemother 2018. doi:10.1093/jac/dkx427 Märtson A, et al. The pharmacokinetics of antibiotics in patients with obesity: a systematic review and consensus guidelines for dose adjustments. Lancet Infect Dis 2025. doi: 10.1016/S1473-3099(25)00155-0 Eagle H and Musselman AD. The rate of bactericidal action of penicillin in vitro as a function of its concentration, and its paradoxically reduced activity at high concentrations against certain organisms. J Exp Med 1948. doi: 10.1084/jem.88.1.99
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In this episode of Communicable, hosts Emily McDonald and Marc Bonten are joined by Sylvain Lother and Valentijn Schweitzer for a discussion on the use of macrolides in community-acquired pneumonia. Together, they examine the evidence for adding a macrolide to beta-lactam therapy, which patients may benefit from combination treatment, and how available evidence can inform clinical practice. Resources: AMMI Canada, https://ammi.ca/en/home/ Further reading Postma DF, et al. Antibiotic Treatment Strategies for Community-Acquired Pneumonia in Adults (CAP-START). NEJM 2015. DOI: 10.1056/NEJMoa1406330 Qian ET, et al. Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With Acute Infection: the ACORN Randomized Clinical Trial. JAMA 2023. DOI: 10.1001/jama.2023.20583 Schweitzer VA, et al. Narrow-spectrum antibiotics for community-acquired pneumonia in Dutch adults (CAP-PACT): a cross-sectional, stepped-wedge, cluster-randomised, non-inferiority, antimicrobial stewardship intervention trial. Lancet Infect Dis 2022. DOI: 10.1016/S1473-3099(21)00255-3 van Daalen FV, et al. Management of community-acquired pneumonia in adults: Practice Guideline from The Dutch Working Party on Antibiotic Policy and Dutch Association of Chest Physicians. CMI Comms 2026. DOI: 10.1016/j.cmicom.2026.105206
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