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Article History

Accepted: 18 August 2021

First Online: 11 December 2021

Declarations

: Preliminary results of parts of this analysis have been presented as abstracts at the annual meetings of the Population Approach Group in Europe (PAGE) 2019 and the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2020 and via oral presentations at the ECCMID 2021 and the International Society of Anti-infective Pharmacology meeting 2021.

: CK and WH have received grants from an industry consortium (AbbVie Deutschland GmbH & Co. KG, AstraZeneca GmbH, Boehringer Ingelheim Pharma GmbH & Co. KG, Grünenthal GmbH, F. Hoffmann-La Roche Ltd, Merck KGaA, and Sanofi) for the PharMetrX program. CK has received grants from the Innovative Medicines Initiative-Joint Undertaking ("DDMoRe”), Diurnal Ltd., the Federal Ministry of Education and Research within the Joint Programming Initiative on Antimicrobial Resistance Initiative (JPIAMR), and the European Commission within the Horizon 2020 framework programme (“FAIR”), all outside the submitted work. HW has received grants from Pfizer (Investigator Initiated Trial Program, Berlin, Germany) and InfectoPharm (Heppenheim, Germany), both for the clinical microdialysis trial, lecture fees from InfectoPharm (Heppenheim, Germany) and MSD (Konstanz, Germany), and consultant honoraria from Dräger Medical (Lübeck, Germany). PS has received grants from Pfizer (Investigator Initiated Trial Program, Berlin, Germany) and InfectoPharm (Heppenheim, Germany), both for the clinical microdialysis trial, and lecture fees from InfectoPharm (Heppenheim, Germany). D. Busse, L. Schmitt, D. Petroff, C. Dorn, A. Dietrich, M. Zeitlinger, and R. Michelet have no conflicts of interest that are directly relevant to the content of this article.

: Open Access funding enabled and organized by Projekt DEAL.

: Approval for the trial was granted by the Leipzig University Ethics committee (No.: 121-13-28012013). The study was also approved by the Federal Institute of Drug and Medical Devices (BfArM – No.: 4038808) and registered in EU clinical trials register (Eudr-CT-No. 2012-004383-22) and German Clinical trials Register (DRKS00004776)<i>.</i> The study was designed following the principles of the Declaration of Helsinki. Written informed consent was obtained from every enrolled patient upon request by the local German law.

: Not applicable.

: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

: The code generated during this analysis is available from the corresponding author on reasonable request.

: DB, RM, and CK designed the data analysis. PS and DP designed and conducted the clinical study and CD performed the assays. DB, RM, and CK performed the data analysis and simulation. DB, PS, LS, DP, CD, WH, RM, HW, and CK discussed the results. DB, LS, RM, and CK drafted the manuscript. All authors commented on and approved the manuscript.