Probability of pharmacological target attainment with flucloxacillin in Staphylococcus aureus bloodstream infection : a prospective cohort study of unbound plasma and individual MICs
© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy..
OBJECTIVES: MSSA bloodstream infections (BSIs) are associated with considerable mortality. Data regarding therapeutic drug monitoring (TDM) and pharmacological target attainment of the β-lactam flucloxacillin are scarce.
PATIENTS AND METHODS: We determined the achievement of pharmacokinetic/pharmacodynamic targets and its association with clinical outcome and potential toxicity in a prospective cohort of 50 patients with MSSA-BSI. Strain-specific MICs and unbound plasma flucloxacillin concentrations (at five different timepoints) were determined by broth microdilution and HPLC-MS, respectively.
RESULTS: In our study population, 48% were critically ill and the 30 day mortality rate was 16%. The median flucloxacillin MIC was 0.125 mg/L. The median unbound trough concentration was 1.7 (IQR 0.4-9.3), 1.9 (IQR 0.4-6.2) and 1.0 (IQR 0.6-3.4) mg/L on study day 1, 3 and 7, respectively. Optimal (100% fT>MIC) and maximum (100% fT>4×MIC) target attainment was achieved in 45 (90%) and 34 (68%) patients, respectively, throughout the study period. Conversely, when using the EUCAST epidemiological cut-off value instead of strain-specific MICs, target attainment was achieved in only 13 (26%) patients. The mean unbound flucloxacillin trough concentration per patient was associated with neurotoxicity (OR 1.12 per 1 mg/L increase, P = 0.02) and significantly higher in deceased patients (median 14.8 versus 1.7 mg/L, P = 0.01).
CONCLUSIONS: Flucloxacillin pharmacological target attainment in MSSA-BSI patients is frequently achieved when unbound flucloxacillin concentrations and strain-specific MICs are considered. However, currently recommended dosing regimens may expose patients to excessive flucloxacillin concentrations, potentially resulting in drug-related organ damage.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:76 |
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| Enthalten in: |
The Journal of antimicrobial chemotherapy - 76(2021), 7 vom: 18. Juni, Seite 1845-1854 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Moser, Stephan [VerfasserIn] |
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| Links: |
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| Themen: |
43B2M34G2V |
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| Anmerkungen: |
Date Completed 01.07.2021 Date Revised 01.07.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/jac/dkab089 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM324150687 |
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| 100 | 1 | |a Moser, Stephan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Probability of pharmacological target attainment with flucloxacillin in Staphylococcus aureus bloodstream infection |b a prospective cohort study of unbound plasma and individual MICs |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Revised 01.07.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. | ||
| 520 | |a OBJECTIVES: MSSA bloodstream infections (BSIs) are associated with considerable mortality. Data regarding therapeutic drug monitoring (TDM) and pharmacological target attainment of the β-lactam flucloxacillin are scarce | ||
| 520 | |a PATIENTS AND METHODS: We determined the achievement of pharmacokinetic/pharmacodynamic targets and its association with clinical outcome and potential toxicity in a prospective cohort of 50 patients with MSSA-BSI. Strain-specific MICs and unbound plasma flucloxacillin concentrations (at five different timepoints) were determined by broth microdilution and HPLC-MS, respectively | ||
| 520 | |a RESULTS: In our study population, 48% were critically ill and the 30 day mortality rate was 16%. The median flucloxacillin MIC was 0.125 mg/L. The median unbound trough concentration was 1.7 (IQR 0.4-9.3), 1.9 (IQR 0.4-6.2) and 1.0 (IQR 0.6-3.4) mg/L on study day 1, 3 and 7, respectively. Optimal (100% fT>MIC) and maximum (100% fT>4×MIC) target attainment was achieved in 45 (90%) and 34 (68%) patients, respectively, throughout the study period. Conversely, when using the EUCAST epidemiological cut-off value instead of strain-specific MICs, target attainment was achieved in only 13 (26%) patients. The mean unbound flucloxacillin trough concentration per patient was associated with neurotoxicity (OR 1.12 per 1 mg/L increase, P = 0.02) and significantly higher in deceased patients (median 14.8 versus 1.7 mg/L, P = 0.01) | ||
| 520 | |a CONCLUSIONS: Flucloxacillin pharmacological target attainment in MSSA-BSI patients is frequently achieved when unbound flucloxacillin concentrations and strain-specific MICs are considered. However, currently recommended dosing regimens may expose patients to excessive flucloxacillin concentrations, potentially resulting in drug-related organ damage | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Rehm, Sophia |e verfasserin |4 aut | |
| 700 | 1 | |a Guertler, Nicolas |e verfasserin |4 aut | |
| 700 | 1 | |a Hinic, Vladimira |e verfasserin |4 aut | |
| 700 | 1 | |a Dräger, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Bassetti, Stefano |e verfasserin |4 aut | |
| 700 | 1 | |a Rentsch, Katharina M |e verfasserin |4 aut | |
| 700 | 1 | |a Sendi, Parham |e verfasserin |4 aut | |
| 700 | 1 | |a Osthoff, Michael |e verfasserin |4 aut | |
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