抗侵袭性真菌病治疗药物监测的研究进展

陈钰婷; 武正华; 范国荣

doi:10.6039/j.issn.1001-0408.2024.20.21

您当前的位置：

首页 >

文章列表页 >

抗侵袭性真菌病治疗药物监测的研究进展

综述 | 更新时间：2024-10-25

- 抗侵袭性真菌病治疗药物监测的研究进展
- Advances in therapeutic drug monitoring of invasive fungal disease
- 中国药房 2024年35卷第20期页码：2565-2570
- 作者机构：
  
  1.上海大学医学院，上海　200444
  2.上海交通大学医学院附属第一人民医院临床药学科，上海　200080
- 作者简介：
  
  硕士研究生。研究方向：治疗药物监测与药物警戒。E-mail：shu_chenyuting@163.com
  主任药师，教授，博士生导师，博士。研究方向：临床药学与个体化药物治疗。E-mail：guorfan@163.com
- 基金信息：
  
  国家自然科学基金资助项目(81973289)
- DOI：10.6039/j.issn.1001-0408.2024.20.21
  中图分类号： R978.5
- 纸质出版日期：2024-10-30，
  
  收稿日期：2024-04-26，
  
  修回日期：2024-09-20，
- 稿件说明：
移动端阅览
陈钰婷,武正华,范国荣.抗侵袭性真菌病治疗药物监测的研究进展 ^Δ[J].中国药房,2024,35(20):2565-2570.

CHEN Yuting,WU Zhenghua,FAN Guorong.Advances in therapeutic drug monitoring of invasive fungal disease[J].ZHONGGUO YAOFANG,2024,35(20):2565-2570.
陈钰婷,武正华,范国荣.抗侵袭性真菌病治疗药物监测的研究进展 ^Δ[J].中国药房,2024,35(20):2565-2570. DOI： 10.6039/j.issn.1001-0408.2024.20.21.

CHEN Yuting,WU Zhenghua,FAN Guorong.Advances in therapeutic drug monitoring of invasive fungal disease[J].ZHONGGUO YAOFANG,2024,35(20):2565-2570. DOI： 10.6039/j.issn.1001-0408.2024.20.21.

摘要

侵袭性真菌病（IFD）是一种深部感染性疾病，在血液系统恶性肿瘤患者中的发病率总体呈上升趋势。三唑类、多烯类、棘白菌素类抗真菌药物以及5-氟胞嘧啶和复方磺胺甲噁唑是临床治疗IFD的主要药物。对这些药物开展治疗药物监测有助于保证药物疗效、减少不良反应的发生。本文系统概述了以上5类药物的有效血药浓度范围，以及血药浓度与疗效和不良反应之间的相关性。固相萃取联合超高效液相色谱串联质谱技术在该研究领域是一种较有前景的检测方法。

Abstract

Invasive fungal disease （IFD） is a deep infectious disease with an overall increasing incidence in patients with hematologic malignancies. Triazoles， polyenes， echinocandins echinocandin antifungal drugs， 5-fluorocytosine and Compound sulfamethoxazole are the main drugs used in the clinical treatment of IFD. Therapeutic drug monitoring for IFD prevention and treatment is helpful to optimize treatment outcomes and reduce adverse effects. In this paper， the effective plasma concentration ranges of the above 5 types of drugs are systematically summarized， and the correlation between the plasma concentration of antifungal drugs and the efficacy and adverse reactions is reviewed. Solid phase extraction combined with ultra-performance chromatography-tandem mass spectrometry is a promising detection method in this research field.

关键词

造血干细胞移植血液系统恶性肿瘤侵袭性真菌病治疗药物监测检测方法

Keywords

hematologic malignanciesinvasive fungal diseasetherapeutic drug monitoringanalytical methods

references

LIEN M Y，YEH S P，GAU J P，et al. High rate of invasive fungal infections after non-T cell depleted haploidentical allo-HSCT even under antifungal prophylaxis[J]. Bone Marrow Transplant，2021，56（7）：1750-1753.

中国医药教育学会真菌病专业委员会，中华医学会血液学分会. 造血干细胞移植后侵袭性真菌病中国专家共识：2023年版[J]. 中华血液学杂志，2023，44（2）：92-97.

Medical Mycology Society of Chinese Medicine and Education Association，Chinese Society of Hematology. Chinese expert consensus for invasive fungal disease in patients after hematopoietic stem cell transplantation：2023[J]. Chin J Hematol，2023，44（2）：92-97.

NOVY E，ROGER C，ROBERTS J A，et al. Pharmacokinetic and pharmacodynamic considerations for antifungal therapy optimisation in the treatment of intra-abdominal candidiasis[J]. Crit Care. 2023，27（1）：449.

陈恳，张相林，克晓燕，等. 《伏立康唑个体化用药指南》解读[J]. 临床药物治疗杂志，2019，17（3）：47-52，78.

CHEN K，ZHANG X L，KE X Y，et al. Executive summary of the Practice Guideline for Individualized Medication of Voriconazole[J]. Clin Med J，2019，17（3）：47-52，78.

MCCREARY E K，DAVIS M R，NARAYANAN N，et al. Utility of triazole antifungal therapeutic drug monitoring：insights from the Society of Infectious Diseases Pharmacists：endorsed by the Mycoses Study Group Education and Research Consortium[J]. Pharmacotherapy，2023，43（10）：1043-1050.

泊沙康唑临床应用专家组. 泊沙康唑临床应用专家共识：2022版[J]. 中华临床感染病杂志，2022，15（5）：321-332.

Working Group of Expert Consensus on Clinical Use of Posaconazole. Expert consensus on clinical use of posaconazole：2022 edition[J]. Chin J Clin Infect Dis，2022，15（5）：321-332.

JOHN J，LOO A，MAZUR S，et al. Therapeutic drug monitoring of systemic antifungal agents：a pragmatic approach for adult and pediatric patients[J]. Expert Opin Drug Metab Toxicol，2019，15（11）：881-895.

ANDES D，KOVANDA L，DESAI A，et al. Isavuconazole concentration in real-world practice：consistency with results from clinical trials[J]. Antimicrob Agents Chemother，2018，62（7）：e00585-e00518.

COJUTTI P G，CARNELUTTI A，LAZZAROTTO D，et al. Population pharmacokinetics and pharmacodynamic target attainment of isavuconazole against Aspergillus fumigatus and Aspergillus flavus in adult patients with invasive fungal diseases：should therapeutic drug monito-ring for isavuconazole be considered as mandatory as for the other mold-active azoles?[J]. Pharmaceutics，2021，13（12）：2099.

FURFARO E，SIGNORI A，DI GRAZIA C，et al. Serial monitoring of isavuconazole blood levels during prolonged antifungal therapy[J]. J Antimicrob Chemother， 2019，74（8）：2341-2346.

PFALLER M A，CARVALHAES C G，CASTANHEIRA M. Susceptibility patterns of amphotericin B，itraco-nazole，posaconazole，voriconazole and caspofungin for isolates causing invasive mould infections from the SENTRY antifungal surveillance program（2018-2021）and application of single-site epidemiological cutoff values to evaluate amphotericin B activity[J]. Mycoses，2023，66（10）：854-868.

LI F Y，ZHOU M G，JIAO Z，et al. Caspofungin pharmacokinetics and probability of target attainment in ICU patients in China[J]. J Glob Antimicrob Resist，2021，25：238-263.

何杰，刘冬雪，钟羚君，等. 重症患者体内米卡芬净暴露量有限采样法估算模型的建立[J]. 中国临床药理学与治疗学，2022，27（11）：1264.

HE J，LIU D X，ZHONG L J，et al. Establishment of a limited sampling strategy to estimate micafungin exposure in critically ill patients[J]. Chin J Clin Pharmacol Ther，2022，27（11）：1264.

康烨，张文涛，阎澜. 米卡芬净预防血液系统恶性肿瘤患者侵袭性真菌感染有效性和安全性的Meta分析[J]. 中国真菌学杂志，2022，17（1）：12-16.

KANG Y，ZHANG W T，YAN L. Efficacy and safety of micafungin in preventing invasive fungal infection in patients with hematological malignancies：a meta-analysis[J]. Chin J Mycol，2022，17（1）：12-16.

KOFLA G，RUHNKE M. Pharmacology and metabolism of anidulafungin，caspofungin and micafungin in the treatment of invasive candidosis：review of the literature[J]. Eur J Med Res，2011，16（4）：159-166.

ABDUL-AZIZ M H，ALFFENAAR J C，BASSETTI M，et al. Antimicrobial therapeutic drug monitoring in critically ill adult patients：a position paper[J]. Intensive Care Med，2020，46（6）：1127-1153.

STOTT K. The pharmacokinetics and pharmacodynamics of antifungal agents for HIV-associated invasive fungal infections[D].Liverpool：University of Liverpool，2021.

RIGHI E，CARNELUTTI A，BACCARANI U，et al. Treatment of Candida infections with fluconazole in adult liver transplant recipients：is TDM-guided dosing adaptation helpful?[J] Transpl Infect Dis，2019，21（4）：e13113.

BOONSTRA J M，MÄRTSON A G，SANDARADURA I，et al. Optimization of fluconazole dosing for the prevention and treatment of invasive candidiasis based on the pharmacokinetics of fluconazole in critically ill patients[J]. Antimicrob Agents Chemother，2021，65（3）：e01554-e01520.

ZHAO H Z，CHENG J H，ZHOU L H，et al. Induction therapy with high-dose fluconazole plus flucytosine for human immunodeficiency virus-uninfected cryptococcal meningitis patients：feasible or not?[J]. Mycoses，2023，66（1）：59-68.

MAERTENS J A，RAHAV G，LEE D G，et al. Pharmacokinetic and exposure response analysis of the double-blind randomized study of posaconazole and voriconazole for treatment of invasive aspergillosis[J]. Clin Drug Investig，2023，43（9）：681-690.

BOPPANA M，SENGAR M，JAIN H，et al. A prospective study to evaluate the effect of therapeutic drug monitoring-based posaconazole prophylaxis on invasive fungal infection rate during acute myeloid leukemia induction therapy[J]. Indian J Hematol Blood Transfus，2024，40（2）：204-212.

WHITMORE T J，YAW M，LAVENDER M，et al. A novel highly bio-available itraconazole formulation（SUBA®- Itraconazole） for anti-fungal prophylaxis in lung transplant recipients[J]. Transpl Infect Dis，2021，23（4）：e13587.

ZHANG J R，LIU Y W，NIE X L，et al. Trough concentration of itraconazole and its relationship with efficacy and safety：a systematic review and meta-analysis[J]. Infect Drug Resist，2018，11：1283-1297.

KOSMIDIS C，OTU A，MOORE C B，et al. Isavuco-nazole therapeutic drug monitoring during long-term treatment for chronic pulmonary aspergillosis[J]. Antimicrob Agents Chemother，2020，65（1）：e01511-e01520.

ABDEL-HAFEZ Y，SIAJ H，JANAJRI M，et al. Tolerabi-lity and epidemiology of nephrotoxicity associated with conventional amphotericin B therapy：a retrospective study in tertiary care centers in Palestine[J]. BMC Nephrol，2022，23（1）：132.

GEERSING T H，FRANSSEN E J F，SPRONK P E，et al. Nephrotoxicity of continuous amphotericin B in critically ill patients with abdominal sepsis：a retrospective analysis with propensity score matching-authors’ response[J]. J Antimicrob Chemother，2022，77（8）：2309-2311.

MARENA G D，RAMOS M A D S，BAUAB T M，et al. A critical review of analytical methods for quantification of amphotericin B in biological samples and pharmaceutical formulations[J]. Crit Rev Anal Chem，2022，52（3）：555-576.

LAI T，YEO C Y，ROCKLIFF B，et al. Therapeutic drug monitoring of liposomal amphotericin B in children. Are we there yet? A systematic review[J]. J Antimicrob Chemother，2024，79（4）：703-711.

KIM H Y，BALDELLI S，MÄRTSON A G，et al. Therapeutic drug monitoring of the echinocandin antifungal agents：is there a role in clinical practice? A position statement of the Anti-infective Drugs Committee of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology[J]. Ther Drug Monit，2022，44（1）：198-214.

周泠宏，王璇，王睿莹，等. 高剂量卡泊芬净治疗侵袭性肺曲霉病的疗效与安全性[J]. 中华传染病杂志，2019，37（3）：139-143.

ZHOU L H，WANG X，WANG R Y，et al. Efficacy and safety of high-dose caspofungin in the treatment of invasive pulmonary aspergillosis[J]. Chin J Infect Dis，2019，37（3）：139-143.

RIVERA-CHAPARRO N D，ERICSON J，WU H L，et al. Safety，effectiveness and exposure-response of micafungin in infants：application of an established pharmacokinetics model to electronic health records[J]. Pediatr Infect Dis J，2019，38（2）：e26-e28.

HARRISON T S，LAWRENCE D S，MWANDUMBA H C，et al. How applicable is the single-dose AMBITION regimen for human immunodeficiency virus-associated cryptococcal meningitis to high-income settings?[J]. Clin Infect Dis，2023，76（5）：944-949.

KATO H，HAGIHARA M，ASAI N，et al. Efficacy of trimethoprim-sulfamethoxazole in combination with an echinocandin as a first-line treatment option for Pneumocystis pneumonia：a systematic review and meta-analysis[J]. Antibiotics，2022，11（6）：719.

用药助手. 复方磺胺甲噁唑片（泻立停）[EB/OL]. [2024-09-12]. https：//drugs.dxy.cn/pc/drug/7ieZtBqmkgeSSGc-552aGyA==?ky=%E6%B3%BB%E7%AB%8B%E5%- 81%9Chttps://drugs.dxy.cn/pc/drug/7ieZtBqmkgeSSGc-552aGyA==?ky=%E6%B3%BB%E7%AB%8B%E5%-81%9C.

Medication assistant. Compound sulfamethoxazole tablets （Diarrhea）[EB/OL].[2024-09-12]. https：//drugs.dxy.cn/pc/drug/7ieZtBqmkgeSSGc552aGyA==?ky=%- E6%B3%BB%E7%AB%8B%E5%81%9Chttps://drugs.dxy.cn/pc/drug/7ieZtBqmkgeSSGc552aGyA==?ky=%-E6%B3%BB%E7%AB%8B%E5%81%9C.

TRUBIN P A，AZAR M M. Current concepts in the diagnosis and management of Pneumocystis pneumonia in solid organ transplantation[J]. Infect Dis Clin North Am，2023，37（3）：617-640.

LI H，LU Y H，TIAN G X，et al. A regimen based on the combination of trimethoprim/sulfamethoxazole with cas-pofungin and corticosteroids as a first-line therapy for patients with severe non-HIV-related Pneumocystis jirovecii pneumonia：a retrospective study in a tertiary hospital[J]. BMC Infect Dis，2024，24（1）：152.

DOWNES K J，GOLDMAN J L. Too much of a good thing：defining antimicrobial therapeutic targets to minimize toxicity[J]. Clin Pharmacol Ther，2021，109（4）：905-917.

WELTE R，OBERACHER H，SCHWÄRZLER B，et al. Quantification of anidulafungin and micafungin in human body fluids by high performance-liquid chromatography with UV-detection[J]. J Chromatogr B Analyt Technol Biomed Life Sci，2020，1139：121937.

FATIGUSO G，FAVATA F，ZEDDA I，et al. A simple high performance liquid chromatography-mass spectrometry method for therapeutic drug monitoring of isavuconazole and four other antifungal drugs in human plasma samples[J]. J Pharm Biomed Anal，2017，145：718-724.

向东，余恒毅，刘璐，等. LC-MS/MS法同时测定伊马替尼、达沙替尼、尼洛替尼及伏立康唑、伊曲康唑、泊沙康唑的血药浓度[J]. 药物分析杂志，2022，42（2）：271-278.

XIANG D，YU H Y，LIU L，et al. Simultaneous determination of imatinib，dasatinib，nilotinib，voriconazole，itraconazole and posaconazole concentration in plasma by LC-MS/MS[J]. Chin J Pharm Anal，2022，42（2）：271-278.

TANAKA R，SHIRAIWA K，TAKANO K，et al. High-throughput simultaneous quantification of five azole anti-fungal agents and one active metabolite in human plasma using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry[J]. Clin Biochem，2022，99：87-96.

LI X J，LI W，LI M，et al. Correlation between enzyme multiplied immunoassay technique and high-performance liquid chromatography in the quantification of vorico-nazole in a paediatric population[J]. Scand J Clin Lab Invest，2021，81（2）：121-126.

BURKIN M A，SUROVOY Y A，ARZUMANIAN V G，et al. Development and application of amphotericin B immunoassay for pharmacokinetic studies and therapeutic drug monitoring in critically ill patients[J]. J Pharm Biomed Anal，2022，218：114875.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

香叶木素的检测方法与生物活性及其机制研究进展