Piperacillin/Tazobactam Dose Optimization in the Setting of Piperacillin/Tazobactam-susceptible, Carbapenem-resistant Pseudomonas aeruginosa : Time to Reconsider Susceptible Dose Dependent
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved..
PURPOSE: This study evaluates the in vitro potency of piperacillin/tazobactam among a global collection of carbapenem-resistant Pseudomonas aeruginosa (CR-PA) and assesses the adequacy of the Clinical and Laboratory Standards Institute (CLSI) P aeruginosa breakpoint dose in the setting of CR-PA using Monte Carlo simulation.
METHODS: Isolates were collected during the Enhancing Rational Antimicrobials Against Carbapenem-Resistant P aeruginosa (ERACE-PA) Global Surveillance Program. Piperacillin/tazobactam MICs were determined using broth microdilution per CLSI standards. A 5000-patient Monte Carlo simulation was performed using various piperacillin/tazobactam dosing regimens to determine the probability of target attainment (PTA) for 50% free time above the MIC. The MIC distribution of piperacillin/tazobactam-susceptible CR-PA was used to calculate cumulative fraction of response (CFR). Optimal PTA and CFR were defined as 90% target achievement.
FINDINGS: A total of 28% of tested CR-PA were piperacillin/tazobactam susceptible. Of these, 71% had MICs of 8 to 16/4 mg/L. Doses of 3.375 g q6h as 0.5-hour infusion (current breakpoint dose) had adequate PTA at MIC of 8/4 mg/L (CFR, 81%); however, extended infusion of 3 or 4 hours improved PTA at 16/4 mg/L (CFR, >90%). Doses of 4.5 g q8h as a 4-hour infusion and 4.5 g q6h as a 3-hour infusion both provide >90% PTA at an MIC of 16 mg/L (CFRs, 97 and 100%, respectively), favoring susceptible dose dependent interpretive criteria with these regimens.
IMPLICATIONS: Although susceptible, piperacillin/ tazobactam has reduced potency in CR-PA. If piperacillin/tazobactam is used for susceptible CR-PA, high-doses (4.5 g q6h) and extended infusion (3 hours or continuous infusion) are needed to optimize exposure.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:45 |
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| Enthalten in: |
Clinical therapeutics - 45(2023), 1 vom: 31. Jan., Seite 72-77 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gill, Christian M [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.02.2023 Date Revised 21.03.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.clinthera.2022.12.004 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a PURPOSE: This study evaluates the in vitro potency of piperacillin/tazobactam among a global collection of carbapenem-resistant Pseudomonas aeruginosa (CR-PA) and assesses the adequacy of the Clinical and Laboratory Standards Institute (CLSI) P aeruginosa breakpoint dose in the setting of CR-PA using Monte Carlo simulation | ||
| 520 | |a METHODS: Isolates were collected during the Enhancing Rational Antimicrobials Against Carbapenem-Resistant P aeruginosa (ERACE-PA) Global Surveillance Program. Piperacillin/tazobactam MICs were determined using broth microdilution per CLSI standards. A 5000-patient Monte Carlo simulation was performed using various piperacillin/tazobactam dosing regimens to determine the probability of target attainment (PTA) for 50% free time above the MIC. The MIC distribution of piperacillin/tazobactam-susceptible CR-PA was used to calculate cumulative fraction of response (CFR). Optimal PTA and CFR were defined as 90% target achievement | ||
| 520 | |a FINDINGS: A total of 28% of tested CR-PA were piperacillin/tazobactam susceptible. Of these, 71% had MICs of 8 to 16/4 mg/L. Doses of 3.375 g q6h as 0.5-hour infusion (current breakpoint dose) had adequate PTA at MIC of 8/4 mg/L (CFR, 81%); however, extended infusion of 3 or 4 hours improved PTA at 16/4 mg/L (CFR, >90%). Doses of 4.5 g q8h as a 4-hour infusion and 4.5 g q6h as a 3-hour infusion both provide >90% PTA at an MIC of 16 mg/L (CFRs, 97 and 100%, respectively), favoring susceptible dose dependent interpretive criteria with these regimens | ||
| 520 | |a IMPLICATIONS: Although susceptible, piperacillin/ tazobactam has reduced potency in CR-PA. If piperacillin/tazobactam is used for susceptible CR-PA, high-doses (4.5 g q6h) and extended infusion (3 hours or continuous infusion) are needed to optimize exposure | ||
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