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...
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MDPI AG
2021-08-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/10/8/993 |
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| author | Ruiying Han Dan Sun Sihan Li Jiaojiao Chen Mengmeng Teng Bo Yang Yalin Dong Taotao Wang |
| author_facet | Ruiying Han Dan Sun Sihan Li Jiaojiao Chen Mengmeng Teng Bo Yang Yalin Dong Taotao Wang |
| author_sort | Ruiying Han |
| collection | DOAJ |
| 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 <i>Enterobacteriaceae</i> and <i>Pseudomonas aeruginosa</i>. For ceftazidime/avibactam, 2000 mg/500 mg/8 h by 4 h infusion achieved >90% CFR for <i>Escherichia coli</i>; even for 4000 mg/1000 mg/6 h by continuous infusion, CFR for <i>Klebsiella pneumoniae</i> 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 <i>Pseudomonas aeruginosa</i>. For ceftolozane/tazobactam, the CFR of standard regimen was >90% for <i>Escherichia coli</i>, however, 2000 mg/1000 mg/6 h by continuous infusion achieved <90% CFRs for <i>Klebsiella pneumoniae</i> and <i>Pseudomonas aeruginosa</i>. For meropenem/vaborbactam, standard regimen achieved optimal attainments for <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i>; 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 <i>Pseudomonas aeruginosa</i>. The CFRs of three BLBLIs were similar for <i>Escherichia coli</i>, but meropenem/vaborbactam were superior for <i>Klebsiella pneumoniae</i> and <i>Pseudomonas aeruginosa</i>. |
| first_indexed | 2024-03-10T09:02:56Z |
| format | Article |
| id | doaj.art-01ae5bfe3efb46d78e8832a5d5212695 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T09:02:56Z |
| publishDate | 2021-08-01 |
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| series | Antibiotics |
| spelling | doaj.art-01ae5bfe3efb46d78e8832a5d52126952023-11-22T06:34:23ZengMDPI AGAntibiotics2079-63822021-08-0110899310.3390/antibiotics10080993Pharmacokinetic/Pharmacodynamic Adequacy of Novel β-Lactam/β-Lactamase Inhibitors against Gram-Negative Bacterial in Critically Ill PatientsRuiying Han0Dan Sun1Sihan Li2Jiaojiao Chen3Mengmeng Teng4Bo Yang5Yalin Dong6Taotao Wang7Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaThe 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 <i>Enterobacteriaceae</i> and <i>Pseudomonas aeruginosa</i>. For ceftazidime/avibactam, 2000 mg/500 mg/8 h by 4 h infusion achieved >90% CFR for <i>Escherichia coli</i>; even for 4000 mg/1000 mg/6 h by continuous infusion, CFR for <i>Klebsiella pneumoniae</i> 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 <i>Pseudomonas aeruginosa</i>. For ceftolozane/tazobactam, the CFR of standard regimen was >90% for <i>Escherichia coli</i>, however, 2000 mg/1000 mg/6 h by continuous infusion achieved <90% CFRs for <i>Klebsiella pneumoniae</i> and <i>Pseudomonas aeruginosa</i>. For meropenem/vaborbactam, standard regimen achieved optimal attainments for <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i>; 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 <i>Pseudomonas aeruginosa</i>. The CFRs of three BLBLIs were similar for <i>Escherichia coli</i>, but meropenem/vaborbactam were superior for <i>Klebsiella pneumoniae</i> and <i>Pseudomonas aeruginosa</i>.https://www.mdpi.com/2079-6382/10/8/993novel β-lactam/β-lactamase inhibitorsGram-negative bacteria infectioncritically ill patientspharmacokinetics/pharmacodynamicsMonte Carlo simulations |
| spellingShingle | Ruiying Han Dan Sun Sihan Li Jiaojiao Chen Mengmeng Teng Bo Yang Yalin Dong Taotao Wang Pharmacokinetic/Pharmacodynamic Adequacy of Novel β-Lactam/β-Lactamase Inhibitors against Gram-Negative Bacterial in Critically Ill Patients Antibiotics novel β-lactam/β-lactamase inhibitors Gram-negative bacteria infection critically ill patients pharmacokinetics/pharmacodynamics Monte Carlo simulations |
| 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 | novel β-lactam/β-lactamase inhibitors Gram-negative bacteria infection critically ill patients pharmacokinetics/pharmacodynamics Monte Carlo simulations |
| url | https://www.mdpi.com/2079-6382/10/8/993 |
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