{"title":"蒙特卡洛模拟用于优化重症患者因产碳青霉烯酶肺炎克雷伯氏菌继发血流感染的最佳治疗剂量。","authors":"Sujareenoot Suya , Worapong Nasomsong , Wichai Santimaleeworagun , Piraporn Juntanawiwat , Tassananwan Chatreewonanakul , Weerayuth Saelim","doi":"10.1016/j.jgar.2024.10.263","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>We aimed to use Monte Carlo simulation, based on pharmacokinetic/pharmacodynamic targets, to investigate and determine the optimal dosage of the available combination therapies for carbapenem-resistant <em>Klebsiella pneumoniae</em> (CRKP) in critically ill patients.</div></div><div><h3>Methods</h3><div>We collected CRKP clinical isolates from Phramongkutklao Hospital between October 2020 and June 2022. A molecular study of resistant genes was performed using polymerase chain reaction. Broth microdilution checkerboards were used to evaluate the mono- and synergistic antibiotic activities. Monte Carlo simulation was used to determine the optimal antibiotic regimens, based on the probability of target attainment (PTA) and cumulative fraction of response.</div></div><div><h3>Results</h3><div>The 54 CRKP isolates were resistant to tigecycline (100%), colistin (75.9%), amikacin (70.4%), and gentamicin (63.0%). The most common carbapenemase genotype was <em>bla<sub>oxacillinases (OXA)-48-like</sub></em> (42.6%), followed by <em>bla<sub>New Delhi metallo beta-lactamase (NDM)</sub></em> (29.6%) and coexistence of <em>bla<sub>OXA-48-like</sub></em> and <em>bla<sub>NDM</sub></em> (22.2%). Based on the PTA, synergistic and additive activities against CRKP isolates were observed with appropriate dosages of tigecycline–colistin (67.9%), tigecycline–gentamicin (62.2%), and tigecycline–amikacin (51.4%).</div></div><div><h3>Conclusions</h3><div>Tigecycline–colistin was the best available combination therapy for critically ill patients with CRKP, especially NDM. When used in combination with tigecycline, a colistin creatinine clearance of <90 mL/min can raise the cumulative fraction of response target and less nephrotoxicity.</div></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":"39 ","pages":"Pages 257-265"},"PeriodicalIF":3.7000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Monte Carlo simulation for dosage optimization of the best available therapy for bloodstream infections secondary to carbapenemase-producing Klebsiella pneumoniae in critically ill patients\",\"authors\":\"Sujareenoot Suya , Worapong Nasomsong , Wichai Santimaleeworagun , Piraporn Juntanawiwat , Tassananwan Chatreewonanakul , Weerayuth Saelim\",\"doi\":\"10.1016/j.jgar.2024.10.263\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><div>We aimed to use Monte Carlo simulation, based on pharmacokinetic/pharmacodynamic targets, to investigate and determine the optimal dosage of the available combination therapies for carbapenem-resistant <em>Klebsiella pneumoniae</em> (CRKP) in critically ill patients.</div></div><div><h3>Methods</h3><div>We collected CRKP clinical isolates from Phramongkutklao Hospital between October 2020 and June 2022. A molecular study of resistant genes was performed using polymerase chain reaction. Broth microdilution checkerboards were used to evaluate the mono- and synergistic antibiotic activities. Monte Carlo simulation was used to determine the optimal antibiotic regimens, based on the probability of target attainment (PTA) and cumulative fraction of response.</div></div><div><h3>Results</h3><div>The 54 CRKP isolates were resistant to tigecycline (100%), colistin (75.9%), amikacin (70.4%), and gentamicin (63.0%). The most common carbapenemase genotype was <em>bla<sub>oxacillinases (OXA)-48-like</sub></em> (42.6%), followed by <em>bla<sub>New Delhi metallo beta-lactamase (NDM)</sub></em> (29.6%) and coexistence of <em>bla<sub>OXA-48-like</sub></em> and <em>bla<sub>NDM</sub></em> (22.2%). Based on the PTA, synergistic and additive activities against CRKP isolates were observed with appropriate dosages of tigecycline–colistin (67.9%), tigecycline–gentamicin (62.2%), and tigecycline–amikacin (51.4%).</div></div><div><h3>Conclusions</h3><div>Tigecycline–colistin was the best available combination therapy for critically ill patients with CRKP, especially NDM. When used in combination with tigecycline, a colistin creatinine clearance of <90 mL/min can raise the cumulative fraction of response target and less nephrotoxicity.</div></div>\",\"PeriodicalId\":15936,\"journal\":{\"name\":\"Journal of global antimicrobial resistance\",\"volume\":\"39 \",\"pages\":\"Pages 257-265\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of global antimicrobial resistance\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2213716524004417\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of global antimicrobial resistance","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2213716524004417","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
Monte Carlo simulation for dosage optimization of the best available therapy for bloodstream infections secondary to carbapenemase-producing Klebsiella pneumoniae in critically ill patients
Objective
We aimed to use Monte Carlo simulation, based on pharmacokinetic/pharmacodynamic targets, to investigate and determine the optimal dosage of the available combination therapies for carbapenem-resistant Klebsiella pneumoniae (CRKP) in critically ill patients.
Methods
We collected CRKP clinical isolates from Phramongkutklao Hospital between October 2020 and June 2022. A molecular study of resistant genes was performed using polymerase chain reaction. Broth microdilution checkerboards were used to evaluate the mono- and synergistic antibiotic activities. Monte Carlo simulation was used to determine the optimal antibiotic regimens, based on the probability of target attainment (PTA) and cumulative fraction of response.
Results
The 54 CRKP isolates were resistant to tigecycline (100%), colistin (75.9%), amikacin (70.4%), and gentamicin (63.0%). The most common carbapenemase genotype was blaoxacillinases (OXA)-48-like (42.6%), followed by blaNew Delhi metallo beta-lactamase (NDM) (29.6%) and coexistence of blaOXA-48-like and blaNDM (22.2%). Based on the PTA, synergistic and additive activities against CRKP isolates were observed with appropriate dosages of tigecycline–colistin (67.9%), tigecycline–gentamicin (62.2%), and tigecycline–amikacin (51.4%).
Conclusions
Tigecycline–colistin was the best available combination therapy for critically ill patients with CRKP, especially NDM. When used in combination with tigecycline, a colistin creatinine clearance of <90 mL/min can raise the cumulative fraction of response target and less nephrotoxicity.
期刊介绍:
The Journal of Global Antimicrobial Resistance (JGAR) is a quarterly online journal run by an international Editorial Board that focuses on the global spread of antibiotic-resistant microbes.
JGAR is a dedicated journal for all professionals working in research, health care, the environment and animal infection control, aiming to track the resistance threat worldwide and provides a single voice devoted to antimicrobial resistance (AMR).
Featuring peer-reviewed and up to date research articles, reviews, short notes and hot topics JGAR covers the key topics related to antibacterial, antiviral, antifungal and antiparasitic resistance.