{"title":"基于模型翻译的持续输注美罗培南降解和输液袋变化对铜绿假单胞菌细菌杀灭的影响。","authors":"Iris K. Minichmayr , Lena E. Friberg","doi":"10.1016/j.ijantimicag.2024.107236","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Continuous infusion of meropenem has been proposed to increase target attainment in critically ill patients, although stability might limit its practical use. This study investigated the impact of meropenem degradation and infusion bag changes on the concentration-time profiles and bacterial growth and killing of <em>P. aeruginosa</em> given different continuous-infusion solutions.</p></div><div><h3>Methods</h3><p>A semi-mechanistic pharmacokinetic-pharmacodynamic (PK-PD) model quantifying meropenem concentrations (C<sub>MEM</sub>) and bacterial counts of a resistant <em>P. aeruginosa</em> strain (ARU552, MIC = 16 mg/L) over 24 h was used to translate <em>in vitro</em> antibiotic effects to patients with severe infections. Concentration-dependent drug degradation of saline infusion solutions was considered using an additional compartment in the population PK model. C<sub>MEM</sub>, <em>f</em>T<sub>>MIC</sub> (time that concentrations exceed the MIC) and total bacterial load (B<sub>TOT</sub>) after 24 h were simulated for different scenarios (<em>n</em> = 144), considering low- and high-dose regimens (3000/6000 mg/day±loading dose), clinically relevant infusion solutions (20/40/50 mg/mL), different intervals of infusion bag changes (every 8/24 h, q8/24 h), and varied renal function (creatinine clearance 40/80/120 mL/min) and MIC values (8/16 mg/L).</p></div><div><h3>Results</h3><p>Highest deviations between changing infusion bags q8h and q24h were observed for 50 mg/mL solutions and scenarios with C<sub>MEM_24</sub><sub>h</sub> close to the MIC, with differences (Δ) in C<sub>MEM_24</sub><sub>h</sub> up to 4.9 mg/L, Δ<em>f</em>T<sub>>MIC</sub>≤65.7%, and ΔB<sub>TOT_24h</sub>≤1.1 log10 CFU/mL, thus affecting conclusions on whether bacteriostasis was reached.</p></div><div><h3>Conclusions</h3><p>In summary, this study indicated that for continuous infusion of meropenem, eight-hourly infusion bag changes improved PK/PD target attainment and might be beneficial particularly for high meropenem concentrations of saline infusion solutions and for plasma concentrations in close proximity to the MIC.</p></div>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9000,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0924857924001547/pdfft?md5=dd614fc2ea7030e2c1e401df78f48619&pid=1-s2.0-S0924857924001547-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Impact of continuous-infusion meropenem degradation and infusion bag changes on bacterial killing of Pseudomonas aeruginosa based on model-informed translation\",\"authors\":\"Iris K. Minichmayr , Lena E. Friberg\",\"doi\":\"10.1016/j.ijantimicag.2024.107236\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Continuous infusion of meropenem has been proposed to increase target attainment in critically ill patients, although stability might limit its practical use. This study investigated the impact of meropenem degradation and infusion bag changes on the concentration-time profiles and bacterial growth and killing of <em>P. aeruginosa</em> given different continuous-infusion solutions.</p></div><div><h3>Methods</h3><p>A semi-mechanistic pharmacokinetic-pharmacodynamic (PK-PD) model quantifying meropenem concentrations (C<sub>MEM</sub>) and bacterial counts of a resistant <em>P. aeruginosa</em> strain (ARU552, MIC = 16 mg/L) over 24 h was used to translate <em>in vitro</em> antibiotic effects to patients with severe infections. Concentration-dependent drug degradation of saline infusion solutions was considered using an additional compartment in the population PK model. C<sub>MEM</sub>, <em>f</em>T<sub>>MIC</sub> (time that concentrations exceed the MIC) and total bacterial load (B<sub>TOT</sub>) after 24 h were simulated for different scenarios (<em>n</em> = 144), considering low- and high-dose regimens (3000/6000 mg/day±loading dose), clinically relevant infusion solutions (20/40/50 mg/mL), different intervals of infusion bag changes (every 8/24 h, q8/24 h), and varied renal function (creatinine clearance 40/80/120 mL/min) and MIC values (8/16 mg/L).</p></div><div><h3>Results</h3><p>Highest deviations between changing infusion bags q8h and q24h were observed for 50 mg/mL solutions and scenarios with C<sub>MEM_24</sub><sub>h</sub> close to the MIC, with differences (Δ) in C<sub>MEM_24</sub><sub>h</sub> up to 4.9 mg/L, Δ<em>f</em>T<sub>>MIC</sub>≤65.7%, and ΔB<sub>TOT_24h</sub>≤1.1 log10 CFU/mL, thus affecting conclusions on whether bacteriostasis was reached.</p></div><div><h3>Conclusions</h3><p>In summary, this study indicated that for continuous infusion of meropenem, eight-hourly infusion bag changes improved PK/PD target attainment and might be beneficial particularly for high meropenem concentrations of saline infusion solutions and for plasma concentrations in close proximity to the MIC.</p></div>\",\"PeriodicalId\":13818,\"journal\":{\"name\":\"International Journal of Antimicrobial Agents\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2024-06-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0924857924001547/pdfft?md5=dd614fc2ea7030e2c1e401df78f48619&pid=1-s2.0-S0924857924001547-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Antimicrobial Agents\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0924857924001547\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Antimicrobial Agents","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0924857924001547","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
Impact of continuous-infusion meropenem degradation and infusion bag changes on bacterial killing of Pseudomonas aeruginosa based on model-informed translation
Background
Continuous infusion of meropenem has been proposed to increase target attainment in critically ill patients, although stability might limit its practical use. This study investigated the impact of meropenem degradation and infusion bag changes on the concentration-time profiles and bacterial growth and killing of P. aeruginosa given different continuous-infusion solutions.
Methods
A semi-mechanistic pharmacokinetic-pharmacodynamic (PK-PD) model quantifying meropenem concentrations (CMEM) and bacterial counts of a resistant P. aeruginosa strain (ARU552, MIC = 16 mg/L) over 24 h was used to translate in vitro antibiotic effects to patients with severe infections. Concentration-dependent drug degradation of saline infusion solutions was considered using an additional compartment in the population PK model. CMEM, fT>MIC (time that concentrations exceed the MIC) and total bacterial load (BTOT) after 24 h were simulated for different scenarios (n = 144), considering low- and high-dose regimens (3000/6000 mg/day±loading dose), clinically relevant infusion solutions (20/40/50 mg/mL), different intervals of infusion bag changes (every 8/24 h, q8/24 h), and varied renal function (creatinine clearance 40/80/120 mL/min) and MIC values (8/16 mg/L).
Results
Highest deviations between changing infusion bags q8h and q24h were observed for 50 mg/mL solutions and scenarios with CMEM_24h close to the MIC, with differences (Δ) in CMEM_24h up to 4.9 mg/L, ΔfT>MIC≤65.7%, and ΔBTOT_24h≤1.1 log10 CFU/mL, thus affecting conclusions on whether bacteriostasis was reached.
Conclusions
In summary, this study indicated that for continuous infusion of meropenem, eight-hourly infusion bag changes improved PK/PD target attainment and might be beneficial particularly for high meropenem concentrations of saline infusion solutions and for plasma concentrations in close proximity to the MIC.
期刊介绍：
The International Journal of Antimicrobial Agents is a peer-reviewed publication offering comprehensive and current reference information on the physical, pharmacological, in vitro, and clinical properties of individual antimicrobial agents, covering antiviral, antiparasitic, antibacterial, and antifungal agents. The journal not only communicates new trends and developments through authoritative review articles but also addresses the critical issue of antimicrobial resistance, both in hospital and community settings. Published content includes solicited reviews by leading experts and high-quality original research papers in the specified fields.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
