Pharmacokinetic/Pharmacodynamic Target Attainment of Vancomycin, at Three Reported Infusion Modes, for Methicillin-Resistant Staphylococcus aureus (MRSA) Bloodstream Infections in Critically Ill Patients: Focus on Novel Infusion Mode
ObjectiveThe study aimed to evaluate and compare the pharmacokinetic/pharmacodynamic (PK/PD) exposure to vancomycin in the novel optimal two-step infusion (OTSI) vs. intermittent infusion (II) vs. continuous infusion (CI) mode, for MRSA bloodstream infections occurring in critical patients.MethodsWi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.874401/full |
| _version_ | 1818113160506245120 |
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| author | Xiangqing Song Mi Han |
| author_facet | Xiangqing Song Mi Han |
| author_sort | Xiangqing Song |
| collection | DOAJ |
| description | ObjectiveThe study aimed to evaluate and compare the pharmacokinetic/pharmacodynamic (PK/PD) exposure to vancomycin in the novel optimal two-step infusion (OTSI) vs. intermittent infusion (II) vs. continuous infusion (CI) mode, for MRSA bloodstream infections occurring in critical patients.MethodsWith PK/PD modeling and Monte Carlo simulations, the PK/PD exposure of 15 OTSI, 13 II, and 6 CI regimens for vancomycin, at 1, 2, 3, 4, 5, and 6 g daily dose, was evaluated. Using the Monte Carlo simulations, the vancomycin population PK parameters derived from critical patients, the PD parameter for MRSA isolates [i.e., minimum inhibitory concentration (MIC)], and the dosing parameters of these regimens were integrated into a robust mdel of vancomycin PK/PD index, defined as a ratio of the daily area under the curve (AUC0–24) to MIC (i.e., AUC0–24/MIC), to estimate the probability of target attainment (PTA) of these regimens against MRSA isolates with an MIC of 0.5, 1, 2, 4, and 8 mg/L in patients with varying renal function. The PTA at an AUC0–24/MIC ratio of >400, 400–600, and >600 was estimated. A regimen with a PTA of ≥90% at an AUC0–24/MIC ratio of 400–600, which is supposed to maximize both efficacy and safety, was considered optimal.ResultsAt the same daily dose, almost only the OTSI regimens showed a PTA of ≥90% at an AUC0–24/MIC ratio of 400–600, and this profile seems evident especially in patients with creatinine clearance (CLcr) of ≥60 ml/min and for isolates with an MIC of ≤2 mg/L. However, for patients with CLcr of <60 ml/min and for isolates with an MIC of ≥4 mg/L, the II regimens often displayed a higher or even ≥90% PTA at an AUC0–24/MIC ratio of >400 and of >600. The CI regimens frequently afforded a reduced PTA at an AUC0–24/MIC ratio of >400 and of >600, regardless of CLcr and MIC.ConclusionsThe data indicated that the OTSI regimens allowed preferred PK/PD exposure in terms of both efficacy and safety, and thus should be focused more on, especially in patients with CLcr of ≥60 ml/min and for isolates with an MIC of ≤2 mg/L. |
| first_indexed | 2024-12-11T03:30:25Z |
| format | Article |
| id | doaj.art-7ad02382606c430285acb50a37ba29dd |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-11T03:30:25Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-7ad02382606c430285acb50a37ba29dd2022-12-22T01:22:23ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-07-011210.3389/fcimb.2022.874401874401Pharmacokinetic/Pharmacodynamic Target Attainment of Vancomycin, at Three Reported Infusion Modes, for Methicillin-Resistant Staphylococcus aureus (MRSA) Bloodstream Infections in Critically Ill Patients: Focus on Novel Infusion ModeXiangqing SongMi HanObjectiveThe study aimed to evaluate and compare the pharmacokinetic/pharmacodynamic (PK/PD) exposure to vancomycin in the novel optimal two-step infusion (OTSI) vs. intermittent infusion (II) vs. continuous infusion (CI) mode, for MRSA bloodstream infections occurring in critical patients.MethodsWith PK/PD modeling and Monte Carlo simulations, the PK/PD exposure of 15 OTSI, 13 II, and 6 CI regimens for vancomycin, at 1, 2, 3, 4, 5, and 6 g daily dose, was evaluated. Using the Monte Carlo simulations, the vancomycin population PK parameters derived from critical patients, the PD parameter for MRSA isolates [i.e., minimum inhibitory concentration (MIC)], and the dosing parameters of these regimens were integrated into a robust mdel of vancomycin PK/PD index, defined as a ratio of the daily area under the curve (AUC0–24) to MIC (i.e., AUC0–24/MIC), to estimate the probability of target attainment (PTA) of these regimens against MRSA isolates with an MIC of 0.5, 1, 2, 4, and 8 mg/L in patients with varying renal function. The PTA at an AUC0–24/MIC ratio of >400, 400–600, and >600 was estimated. A regimen with a PTA of ≥90% at an AUC0–24/MIC ratio of 400–600, which is supposed to maximize both efficacy and safety, was considered optimal.ResultsAt the same daily dose, almost only the OTSI regimens showed a PTA of ≥90% at an AUC0–24/MIC ratio of 400–600, and this profile seems evident especially in patients with creatinine clearance (CLcr) of ≥60 ml/min and for isolates with an MIC of ≤2 mg/L. However, for patients with CLcr of <60 ml/min and for isolates with an MIC of ≥4 mg/L, the II regimens often displayed a higher or even ≥90% PTA at an AUC0–24/MIC ratio of >400 and of >600. The CI regimens frequently afforded a reduced PTA at an AUC0–24/MIC ratio of >400 and of >600, regardless of CLcr and MIC.ConclusionsThe data indicated that the OTSI regimens allowed preferred PK/PD exposure in terms of both efficacy and safety, and thus should be focused more on, especially in patients with CLcr of ≥60 ml/min and for isolates with an MIC of ≤2 mg/L.https://www.frontiersin.org/articles/10.3389/fcimb.2022.874401/fullvancomycinmethicillin-resistant Staphylococcus aureuspharmacokinetic/pharmacodynamiccontinuous infusionintermittent infusionoptimal infusion |
| spellingShingle | Xiangqing Song Mi Han Pharmacokinetic/Pharmacodynamic Target Attainment of Vancomycin, at Three Reported Infusion Modes, for Methicillin-Resistant Staphylococcus aureus (MRSA) Bloodstream Infections in Critically Ill Patients: Focus on Novel Infusion Mode Frontiers in Cellular and Infection Microbiology vancomycin methicillin-resistant Staphylococcus aureus pharmacokinetic/pharmacodynamic continuous infusion intermittent infusion optimal infusion |
| title | Pharmacokinetic/Pharmacodynamic Target Attainment of Vancomycin, at Three Reported Infusion Modes, for Methicillin-Resistant Staphylococcus aureus (MRSA) Bloodstream Infections in Critically Ill Patients: Focus on Novel Infusion Mode |
| title_full | Pharmacokinetic/Pharmacodynamic Target Attainment of Vancomycin, at Three Reported Infusion Modes, for Methicillin-Resistant Staphylococcus aureus (MRSA) Bloodstream Infections in Critically Ill Patients: Focus on Novel Infusion Mode |
| title_fullStr | Pharmacokinetic/Pharmacodynamic Target Attainment of Vancomycin, at Three Reported Infusion Modes, for Methicillin-Resistant Staphylococcus aureus (MRSA) Bloodstream Infections in Critically Ill Patients: Focus on Novel Infusion Mode |
| title_full_unstemmed | Pharmacokinetic/Pharmacodynamic Target Attainment of Vancomycin, at Three Reported Infusion Modes, for Methicillin-Resistant Staphylococcus aureus (MRSA) Bloodstream Infections in Critically Ill Patients: Focus on Novel Infusion Mode |
| title_short | Pharmacokinetic/Pharmacodynamic Target Attainment of Vancomycin, at Three Reported Infusion Modes, for Methicillin-Resistant Staphylococcus aureus (MRSA) Bloodstream Infections in Critically Ill Patients: Focus on Novel Infusion Mode |
| title_sort | pharmacokinetic pharmacodynamic target attainment of vancomycin at three reported infusion modes for methicillin resistant staphylococcus aureus mrsa bloodstream infections in critically ill patients focus on novel infusion mode |
| topic | vancomycin methicillin-resistant Staphylococcus aureus pharmacokinetic/pharmacodynamic continuous infusion intermittent infusion optimal infusion |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.874401/full |
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