{"title":"治疗不同肾功能程度的重症患者中耐碳青霉烯类鲍曼不动杆菌的优化磷霉素方案。","authors":"Nattapong Tidwong, Anan Chanruang, Suthanya Chupradit, Suzanne L. Parker, Pannee Leelawattanachai, Poramed Winichakoon, Baralee Punyawudho","doi":"10.1111/cts.70038","DOIUrl":null,"url":null,"abstract":"<p>Fosfomycin has been used to treat carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) infections. However, there is insufficient information on dosage adjustment among critically ill patients with renal impairment. This study aims to evaluate the attainment of PK/PD targets for different dosage regimens of CRAB treatment in critically ill patients based on their renal function. Monte Carlo simulations were conducted to assess the probability of achieving time above the minimum inhibitory concentration (T > MIC) of 80% and 100% and to determine the cumulative fraction response (CFR) against institutional MICs. Our results demonstrated that administering fosfomycin 20–24 g/day to individuals with normal renal function (CrCl ≥60 mL/min) achieved the target at a MIC of ≤64 and ≤32 μg/mL during the first 24 h of treatment and at steady state, respectively. Notably, those with renal impairment achieved higher MIC values at a steady state despite dosage reduction. None of the regimens reached the target CFR. Our study suggested that administering fosfomycin at least 20 g/day to those with normal renal function provides sufficient exposure throughout the treatment course when the MIC value is ≤32 μg/mL. Less aggressive dosing regimens are advisable for patients with renal impairment. Additional clinical studies are necessary to verify our suggestions.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 10","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70038","citationCount":"0","resultStr":"{\"title\":\"Optimized fosfomycin regimens for treating carbapenem-resistant Acinetobacter baumannii in critically ill patients with varying degrees of renal function\",\"authors\":\"Nattapong Tidwong, Anan Chanruang, Suthanya Chupradit, Suzanne L. Parker, Pannee Leelawattanachai, Poramed Winichakoon, Baralee Punyawudho\",\"doi\":\"10.1111/cts.70038\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Fosfomycin has been used to treat carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) infections. However, there is insufficient information on dosage adjustment among critically ill patients with renal impairment. This study aims to evaluate the attainment of PK/PD targets for different dosage regimens of CRAB treatment in critically ill patients based on their renal function. Monte Carlo simulations were conducted to assess the probability of achieving time above the minimum inhibitory concentration (T > MIC) of 80% and 100% and to determine the cumulative fraction response (CFR) against institutional MICs. Our results demonstrated that administering fosfomycin 20–24 g/day to individuals with normal renal function (CrCl ≥60 mL/min) achieved the target at a MIC of ≤64 and ≤32 μg/mL during the first 24 h of treatment and at steady state, respectively. Notably, those with renal impairment achieved higher MIC values at a steady state despite dosage reduction. None of the regimens reached the target CFR. Our study suggested that administering fosfomycin at least 20 g/day to those with normal renal function provides sufficient exposure throughout the treatment course when the MIC value is ≤32 μg/mL. Less aggressive dosing regimens are advisable for patients with renal impairment. Additional clinical studies are necessary to verify our suggestions.</p>\",\"PeriodicalId\":50610,\"journal\":{\"name\":\"Cts-Clinical and Translational Science\",\"volume\":\"17 10\",\"pages\":\"\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2024-09-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70038\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cts-Clinical and Translational Science\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/cts.70038\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cts-Clinical and Translational Science","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cts.70038","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
摘要
磷霉素已被用于治疗耐碳青霉烯类鲍曼不动杆菌(CRAB)感染。然而,有关肾功能受损的重症患者剂量调整的信息尚不充分。本研究旨在根据重症患者的肾功能,评估不同剂量方案治疗 CRAB 的 PK/PD 目标的实现情况。我们进行了蒙特卡洛模拟,以评估达到最小抑制浓度(T > MIC)80%和100%以上时间的概率,并确定针对机构MIC的累积分数反应(CFR)。我们的研究结果表明,对肾功能正常(CrCl ≥60 mL/min)的患者每天给予 20-24 克磷霉素,在治疗的最初 24 小时内和稳定状态下,其 MIC 分别为 ≤64 和 ≤32 μg/mL,均能达到目标。值得注意的是,肾功能受损者尽管减少了剂量,但在稳定状态下的 MIC 值更高。所有方案均未达到目标 CFR。我们的研究表明,当 MIC 值≤32 μg/mL 时,肾功能正常者每天至少服用 20 克磷霉素可在整个疗程中获得足够的暴露量。对于肾功能受损的患者,建议采用较温和的给药方案。有必要进行更多的临床研究来验证我们的建议。
Optimized fosfomycin regimens for treating carbapenem-resistant Acinetobacter baumannii in critically ill patients with varying degrees of renal function
Fosfomycin has been used to treat carbapenem-resistant Acinetobacter baumannii (CRAB) infections. However, there is insufficient information on dosage adjustment among critically ill patients with renal impairment. This study aims to evaluate the attainment of PK/PD targets for different dosage regimens of CRAB treatment in critically ill patients based on their renal function. Monte Carlo simulations were conducted to assess the probability of achieving time above the minimum inhibitory concentration (T > MIC) of 80% and 100% and to determine the cumulative fraction response (CFR) against institutional MICs. Our results demonstrated that administering fosfomycin 20–24 g/day to individuals with normal renal function (CrCl ≥60 mL/min) achieved the target at a MIC of ≤64 and ≤32 μg/mL during the first 24 h of treatment and at steady state, respectively. Notably, those with renal impairment achieved higher MIC values at a steady state despite dosage reduction. None of the regimens reached the target CFR. Our study suggested that administering fosfomycin at least 20 g/day to those with normal renal function provides sufficient exposure throughout the treatment course when the MIC value is ≤32 μg/mL. Less aggressive dosing regimens are advisable for patients with renal impairment. Additional clinical studies are necessary to verify our suggestions.
期刊介绍:
Clinical and Translational Science (CTS), an official journal of the American Society for Clinical Pharmacology and Therapeutics, highlights original translational medicine research that helps bridge laboratory discoveries with the diagnosis and treatment of human disease. Translational medicine is a multi-faceted discipline with a focus on translational therapeutics. In a broad sense, translational medicine bridges across the discovery, development, regulation, and utilization spectrum. Research may appear as Full Articles, Brief Reports, Commentaries, Phase Forwards (clinical trials), Reviews, or Tutorials. CTS also includes invited didactic content that covers the connections between clinical pharmacology and translational medicine. Best-in-class methodologies and best practices are also welcomed as Tutorials. These additional features provide context for research articles and facilitate understanding for a wide array of individuals interested in clinical and translational science. CTS welcomes high quality, scientifically sound, original manuscripts focused on clinical pharmacology and translational science, including animal, in vitro, in silico, and clinical studies supporting the breadth of drug discovery, development, regulation and clinical use of both traditional drugs and innovative modalities.