Cargando…

Pharmacokinetic/Pharmacodynamic Adequacy of Novel β-Lactam/β-Lactamase Inhibitors against Gram-Negative Bacterial in Critically Ill Patients

The optimal regimens of novel β-lactam/β-lactamase inhibitors (BLBLIs), ceftazidime/avibactam, ceftolozane/tazobactam, and meropenem/vaborbactam, are not well defined in critically ill patients. This study was conducted to identify optimal regimens of BLBLIs in these patients. A Monte Carlo simulati...

Descripción completa

Detalles Bibliográficos
Autores principales: Han, Ruiying, Sun, Dan, Li, Sihan, Chen, Jiaojiao, Teng, Mengmeng, Yang, Bo, Dong, Yalin, Wang, Taotao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389032/
https://www.ncbi.nlm.nih.gov/pubmed/34439043
http://dx.doi.org/10.3390/antibiotics10080993
_version_ 1783742771474989056
author Han, Ruiying
Sun, Dan
Li, Sihan
Chen, Jiaojiao
Teng, Mengmeng
Yang, Bo
Dong, Yalin
Wang, Taotao
author_facet Han, Ruiying
Sun, Dan
Li, Sihan
Chen, Jiaojiao
Teng, Mengmeng
Yang, Bo
Dong, Yalin
Wang, Taotao
author_sort Han, Ruiying
collection PubMed
description The optimal regimens of novel β-lactam/β-lactamase inhibitors (BLBLIs), ceftazidime/avibactam, ceftolozane/tazobactam, and meropenem/vaborbactam, are not well defined in critically ill patients. This study was conducted to identify optimal regimens of BLBLIs in these patients. A Monte Carlo simulation was performed using the published data to calculate the joint probability of target attainment (PTA) and the cumulative fraction of response (CFR). For the target of β-lactam of 100% time with free drug concentration remains above minimal inhibitory concentrations, the PTAs of BLBLIs standard regimens were <90% at a clinical breakpoint for Enterobacteriaceae and Pseudomonas aeruginosa. For ceftazidime/avibactam, 2000 mg/500 mg/8 h by 4 h infusion achieved >90% CFR for Escherichia coli; even for 4000 mg/1000 mg/6 h by continuous infusion, CFR for Klebsiella pneumoniae was <90%; the CFRs of 3500 mg/875 mg/6 h by 4 h infusion and 4000 mg/1000 mg/8 h by continuous infusion were appropriate for Pseudomonas aeruginosa. For ceftolozane/tazobactam, the CFR of standard regimen was >90% for Escherichia coli, however, 2000 mg/1000 mg/6 h by continuous infusion achieved <90% CFRs for Klebsiella pneumoniae and Pseudomonas aeruginosa. For meropenem/vaborbactam, standard regimen achieved optimal attainments for Escherichia coli and Klebsiella pneumoniae; 2000 mg/2000 mg/6 h by 5 h infusion, 2500 mg /2500 mg/6 h by 4 h infusion, 3000 mg/3000 mg/6 h by 3 h infusion and 4000 mg/4000 mg/8 h by 5 h infusion achieved >90% CFRs for Pseudomonas aeruginosa. The CFRs of three BLBLIs were similar for Escherichia coli, but meropenem/vaborbactam were superior for Klebsiella pneumoniae and Pseudomonas aeruginosa.
format Online
Article
Text
id pubmed-8389032
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-83890322021-08-27 Pharmacokinetic/Pharmacodynamic Adequacy of Novel β-Lactam/β-Lactamase Inhibitors against Gram-Negative Bacterial in Critically Ill Patients Han, Ruiying Sun, Dan Li, Sihan Chen, Jiaojiao Teng, Mengmeng Yang, Bo Dong, Yalin Wang, Taotao Antibiotics (Basel) Article The optimal regimens of novel β-lactam/β-lactamase inhibitors (BLBLIs), ceftazidime/avibactam, ceftolozane/tazobactam, and meropenem/vaborbactam, are not well defined in critically ill patients. This study was conducted to identify optimal regimens of BLBLIs in these patients. A Monte Carlo simulation was performed using the published data to calculate the joint probability of target attainment (PTA) and the cumulative fraction of response (CFR). For the target of β-lactam of 100% time with free drug concentration remains above minimal inhibitory concentrations, the PTAs of BLBLIs standard regimens were <90% at a clinical breakpoint for Enterobacteriaceae and Pseudomonas aeruginosa. For ceftazidime/avibactam, 2000 mg/500 mg/8 h by 4 h infusion achieved >90% CFR for Escherichia coli; even for 4000 mg/1000 mg/6 h by continuous infusion, CFR for Klebsiella pneumoniae was <90%; the CFRs of 3500 mg/875 mg/6 h by 4 h infusion and 4000 mg/1000 mg/8 h by continuous infusion were appropriate for Pseudomonas aeruginosa. For ceftolozane/tazobactam, the CFR of standard regimen was >90% for Escherichia coli, however, 2000 mg/1000 mg/6 h by continuous infusion achieved <90% CFRs for Klebsiella pneumoniae and Pseudomonas aeruginosa. For meropenem/vaborbactam, standard regimen achieved optimal attainments for Escherichia coli and Klebsiella pneumoniae; 2000 mg/2000 mg/6 h by 5 h infusion, 2500 mg /2500 mg/6 h by 4 h infusion, 3000 mg/3000 mg/6 h by 3 h infusion and 4000 mg/4000 mg/8 h by 5 h infusion achieved >90% CFRs for Pseudomonas aeruginosa. The CFRs of three BLBLIs were similar for Escherichia coli, but meropenem/vaborbactam were superior for Klebsiella pneumoniae and Pseudomonas aeruginosa. MDPI 2021-08-17 /pmc/articles/PMC8389032/ /pubmed/34439043 http://dx.doi.org/10.3390/antibiotics10080993 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Han, Ruiying
Sun, Dan
Li, Sihan
Chen, Jiaojiao
Teng, Mengmeng
Yang, Bo
Dong, Yalin
Wang, Taotao
Pharmacokinetic/Pharmacodynamic Adequacy of Novel β-Lactam/β-Lactamase Inhibitors against Gram-Negative Bacterial in Critically Ill Patients
title Pharmacokinetic/Pharmacodynamic Adequacy of Novel β-Lactam/β-Lactamase Inhibitors against Gram-Negative Bacterial in Critically Ill Patients
title_full Pharmacokinetic/Pharmacodynamic Adequacy of Novel β-Lactam/β-Lactamase Inhibitors against Gram-Negative Bacterial in Critically Ill Patients
title_fullStr Pharmacokinetic/Pharmacodynamic Adequacy of Novel β-Lactam/β-Lactamase Inhibitors against Gram-Negative Bacterial in Critically Ill Patients
title_full_unstemmed Pharmacokinetic/Pharmacodynamic Adequacy of Novel β-Lactam/β-Lactamase Inhibitors against Gram-Negative Bacterial in Critically Ill Patients
title_short Pharmacokinetic/Pharmacodynamic Adequacy of Novel β-Lactam/β-Lactamase Inhibitors against Gram-Negative Bacterial in Critically Ill Patients
title_sort pharmacokinetic/pharmacodynamic adequacy of novel β-lactam/β-lactamase inhibitors against gram-negative bacterial in critically ill patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389032/
https://www.ncbi.nlm.nih.gov/pubmed/34439043
http://dx.doi.org/10.3390/antibiotics10080993
work_keys_str_mv AT hanruiying pharmacokineticpharmacodynamicadequacyofnovelblactamblactamaseinhibitorsagainstgramnegativebacterialincriticallyillpatients
AT sundan pharmacokineticpharmacodynamicadequacyofnovelblactamblactamaseinhibitorsagainstgramnegativebacterialincriticallyillpatients
AT lisihan pharmacokineticpharmacodynamicadequacyofnovelblactamblactamaseinhibitorsagainstgramnegativebacterialincriticallyillpatients
AT chenjiaojiao pharmacokineticpharmacodynamicadequacyofnovelblactamblactamaseinhibitorsagainstgramnegativebacterialincriticallyillpatients
AT tengmengmeng pharmacokineticpharmacodynamicadequacyofnovelblactamblactamaseinhibitorsagainstgramnegativebacterialincriticallyillpatients
AT yangbo pharmacokineticpharmacodynamicadequacyofnovelblactamblactamaseinhibitorsagainstgramnegativebacterialincriticallyillpatients
AT dongyalin pharmacokineticpharmacodynamicadequacyofnovelblactamblactamaseinhibitorsagainstgramnegativebacterialincriticallyillpatients
AT wangtaotao pharmacokineticpharmacodynamicadequacyofnovelblactamblactamaseinhibitorsagainstgramnegativebacterialincriticallyillpatients