(ISAP), the PK/PD study group of the European Society of Clinical Microbiology, Infectious Diseases (EPASG) Therapeutic drug monitoring (TDM) and model-informed precision dosing (MIPD) have evolved as important tools to inform rational dosing of antibiotics in individual patients with infections. In particular, critically ill patients display altered, highly variable pharmacokinetics and often suffer from infections caused by less susceptible bacteria. Consequently, TDM has been used to individualize dosing in this patient group for many years. More recently, there has been increasing research on the use of MIPD software to streamline the TDM process, which can increase the flexibility and precision of dose individualization but also requires adequate model validation and re-evaluation of existing workflows. In parallel, new minimally invasive and noninvasive technologies such as microneedle-based sensors are being developed, which-together with MIPD software-have the potential to revolutionize how patients are dosed with antibiotics. Nonetheless, carefully designed clinical trials to evaluate the benefit of TDM and MIPD approaches are still sparse, but are critically needed to justify the implementation of TDM and MIPD in clinical practice. The present review summarizes the clinical pharmacology of antibiotics, conventional TDM and MIPD approaches, and evidence of the value of TDM/MIPD for aminoglycosides, beta-lactams, glycopeptides, and linezolid, for which precision dosing approaches have been recommended.

Conflict of Interest SNH is a co-founder of Juvabis AG, a startup biotech company with an interest in aminoglycoside therapeutics. All other authors declared no competing interests for this work. Funding Some of the research leading to these results was conducted as part of the ND4BB European Gram-Negative Antibacterial Engine (ENABLE) Consortium (www.nd4bb-enable.eu) and has received funding from the Innovative Medicines Initiative Joint Undertaking under grant agreement n°115583, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme

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Model‐informed drug development (MIDD) has a long and rich history in infectious diseases. This review describes foundational principles of translational anti‐infective pharmacology, including choice of appropriate measures of exposure and pharmacodynamic (PD) measures, patient subpopulations, and drug‐drug interactions. Examples are presented for state‐of‐the‐art, empiric, mechanistic, interdisciplinary, and real‐world evidence MIDD applications in the development of antibacterials (review of minimum inhibitory concentration‐based models, mechanism‐based pharmacokinetic/PD (PK/PD) models, PK/PD models of resistance, and immune response), antifungals, antivirals, drugs for the treatment of global health infectious diseases, and medical countermeasures. The degree of adoption of MIDD practices across the infectious diseases field is also summarized. The future application of MIDD in infectious diseases will progress along two planes; “depth” and “breadth” of MIDD methods. “MIDD depth” refers to deeper incorporation of the specific pathogen biology and intrinsic and acquired‐resistance mechanisms; host factors, such as immunologic response and infection site, to enable deeper interrogation of pharmacological impact on pathogen clearance; clinical outcome and emergence of resistance from a pathogen; and patient and population perspective. In particular, improved early assessment of the emergence of resistance potential will become a greater focus in MIDD, as this is poorly mitigated by current development approaches. “MIDD breadth” refers to greater adoption of model‐centered approaches to anti‐infective development. Specifically, this means how various MIDD approaches and translational tools can be integrated or connected in a systematic way that supports decision making by key stakeholders (sponsors, regulators, and payers) across the entire development pathway.

patients treated with colistin monotherapy, synergism was not protective against 14-day clinical failure (aOR 0.52, 95% CI 0.26e1.04) or 14-day mortality (aOR1.09, 95% CI 0.60e1.96). Discussion: In vitro synergism between colistin and meropenem via checkerboard method did not translate into clinical benefit.