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. 2021 Sep 28;12:5691. doi: 10.1038/s41467-021-25927-3

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 10 — A Initial pharmacokinetic (PK) profiles of mono or multi-drug treatments using two hypothetical antibiotics D_A (turquoise) and D_B (purple) where both drugs follow one-compartmental kinetics with first-order elimination. The drugs were administrated intravenously twice daily according to four different treatment schedules (columns), including non-reparative sequential administration, repetitive cycling administration, and simulations administration. Dosages used were related to average steady-state concentration of 1.5 mg/L (1.5 x MIC_WT) or 0.75 mg/L (0.75 x MIC_WT) for simultaneous dosing. B Pharmacodynamic profiles related to different treatment schedules using different antibiotic drug types including concentration- (Hill = 3, red) or time- (Hill = 0.5, blue) dependent antibiotics and bactericidal (G_min = −3, solid) and bacteriostatic (G_min = −1, dashed), where the effect is representing the proportional bacterial growth inhibition/killing of different bacterial phenotypes (rows). The bacterial phenotypes are associated with different sensitivities towards D_A and D_B. The effect is driven by the PK profile shown in panel A according to Eqs. (9) and (10).