Study on the correlation of peak blood concentrations of compound sulfamethoxazole and its metabolites with clinical efficacy and adverse reactions in critically ill patients

FU Xiangxiang; ZHONG Lili; GU Jiangfan; MEI Mengyu; LI Xinxin; DENG Yang; WANG Min

doi:10.6039/j.issn.1001-0408.2025.14.15

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Study on the correlation of peak blood concentrations of compound sulfamethoxazole and its metabolites with clinical efficacy and adverse reactions in critically ill patients

更新时间：2025-09-24

- Study on the correlation of peak blood concentrations of compound sulfamethoxazole and its metabolites with clinical efficacy and adverse reactions in critically ill patients
- ZHONGGUO YAOFANG Vol. 36, Issue 14, Pages: 1775-1780(2025)
- 作者机构：
  
  1.海南医科大学药学院，海口　571199
  2.长沙市第三医院抗耐药微生物药物湖南省重点实验室，长沙　410015
  3.海南省人民医院/海南医科大学附属海南医院药学部，海口　570311
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2025.14.15
  CLC： R978.2
- Received：11 March 2025，
  
  Revised：2025-06-06，
  
  Accepted：11 June 2025，
  
  Published：30 July 2025
- 稿件说明：
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符香香,钟莉莉,顾江帆,等.复方磺胺甲噁唑及其代谢物血药峰浓度与危重症患者临床疗效及不良反应的相关性研究[J].中国药房,2025,36(14):1775-1780.

FU Xiangxiang,ZHONG Lili,GU Jiangfan,et al.Study on the correlation of peak blood concentrations of compound sulfamethoxazole and its metabolites with clinical efficacy and adverse reactions in critically ill patients[J].ZHONGGUO YAOFANG,2025,36(14):1775-1780.
符香香,钟莉莉,顾江帆,等.复方磺胺甲噁唑及其代谢物血药峰浓度与危重症患者临床疗效及不良反应的相关性研究[J].中国药房,2025,36(14):1775-1780. DOI： 10.6039/j.issn.1001-0408.2025.14.15.

FU Xiangxiang,ZHONG Lili,GU Jiangfan,et al.Study on the correlation of peak blood concentrations of compound sulfamethoxazole and its metabolites with clinical efficacy and adverse reactions in critically ill patients[J].ZHONGGUO YAOFANG,2025,36(14):1775-1780. DOI： 10.6039/j.issn.1001-0408.2025.14.15.

摘要

目的

分析复方磺胺甲噁唑（简称“TMP/SMZ”）及其代谢物

-乙酰基磺胺甲噁唑（NSMZ）血药峰浓度（

max

）与危重症患者临床疗效及不良反应的相关性。

方法

回顾性收集2023年12月至2025年1月海南省人民医院重症监护室（ICU）使用TMP/SMZ治疗的危重症患者资料，按治疗后是否成功分为成功组和失败组。采用简单线性回归和Spearman相关分析法分析TMP

max

、SMZ

max

及NSMZ

max

与临床疗效及不良反应的相关性；采用受试者工作特征曲线（ROC）预测不良反应发生时的截断值。

结果

在入住ICU 24 h内急性生理与慢性健康评分Ⅱ（APACHE-Ⅱ）≥15分的危重症患者中，成功组患者的SMZ

max

显著高于失败组（

＜0.05）。TMP/SMZ每日总剂量与TMP

max

、SMZ

max

呈正相关（

＜0.05）。TMP

max

与肝毒性和肾毒性、SMZ

max

与肝毒性、NSMZ

max

与肾毒性有相关性（

＜0.05）。TMP

max

预测肾毒性和肝毒性的截断值分别为7.25、6.63 μg/mL，SMZ

max

预测肝毒性的截断值为138.00 μg/mL，NSMZ

max

预测肾毒性的截断值为60.76 μg/mL。

结论

入住ICU 24 h内APACHE-Ⅱ≥15分的危重症患者中，SMZ

max

与治疗成功存在关联。TMP

max

≥6.63 μg/mL、SMZ

max

≥138.00 μg/mL时，患者的肝毒性发生风险显著增加；TMP

max

≥7.25 μg/mL、NSMZ

max

≥60.76 μg/mL时，患者的肾毒性发生风险显著增加。

Abstract

OBJECTIVE

To analyze the correlation of the peak blood concentration （

max

） of compound sulfamethoxazole （TMP/SMZ） and its metabolite

-acetyl sulfamethoxazole （NSMZ） with clinical efficacy and adverse reactions in critically ill patients.

METHODS

The data of critically ill patients treated with TMP/SMZ in various ICU of Hainan General Hospital from December 2023 to January 2025 were retrospectively collected. The patients were divided into success group and failure group based on the treatment outcome. Simple linear regression and Spearman correlation analysis were used to analyze the correlation of TMP

max

， SMZ

max

， and NSMZ

max

with clinical efficacy and adverse reactions. The receiver operating characteristic curve （ROC） was used to determine the cutoff values of

max

for predicting the occurrence of adverse reactions.

RESULTS

Among critically ill patients with an acute physiology and chronic health evaluation Ⅱ （APACHE-Ⅱ） ≥15 points 24 h of check-in at ICU， SMZ

max

of success group was significantly higher than failure group （

＜0.05）. The daily total dose of TMP/SMZ was positively correlated with TMP

max

and SMZ

max

（

＜0.05）. TMP

max

was significantly correlated with hepatotoxicity and nephrotoxicity， SMZ

max

with hepatotoxicity， and NSMZ

max

with nephrotoxicity （

＜0.05）. The cutoff values of TMP

max

for predicting nephrotoxicity and hepatotoxicity were 7.25 μg/mL and 6.63 μg/mL， respectively. The cutoff value of SMZ

max

for predicting hepatotoxicity was 138.00 μg/mL， and that of NSMZ

max

for predicting nephrotoxicity was 60.76 μg/mL.

CONCLUSIONS

Among critically ill patients with an APACHE-Ⅱ ≥15 points 24 h of check-in at ICU， SMZ

max

is associated with treatment success. Hepatotoxicity risk significantly increases when TMP

max

≥6.63 μg/mL or SMZ

max

≥138.00 μg/mL； nephrotoxicity risk significantly increases when TMP

max

≥7.25 μg/mL or NSMZ

max

≥60.76 μg/mL.

关键词

Keywords

references

BURCHALL J J . Mechanism of action of trimethoprim-sulfamethoxazole：Ⅱ [J ] . J Infect Dis ， 1973 ， 128 ： 437 - 441 .

MCKINDLEY D S ， HANES S ， BOUCHER B A . Hepatic drug metabolism in critical illness [J ] . Pharmacotherapy ， 1998 ， 18 （ 4 ）： 759 - 778 .

SMITH B S ， YOGARATNAM D ， LEVASSEUR-FRANKLIN K E ， et al . Introduction to drug pharmacokinetics in the critically ill patient [J ] . Chest ， 2012 ， 141 （ 5 ）： 1327 - 1336 .

BOUCHER B A ， CHRISTOPHER WOOD G ， SWANSON J M . Pharmacokinetic changes in critical illness [J ] . Crit Care Clin ， 2006 ， 22 （ 2 ）： 255 - 271 .

HIRAI T ， YAMAGA R ， ISHIKAWA Y ， et al . Effect of high-dose sulfamethoxazole/trimethoprim and glucocorticoid use on hyperkalemic event：a retrospective observational study [J ] . J Infect Chemother ， 2021 ， 27 （ 11 ）： 1607 - 1613 .

GOLDMAN J L ， VAN HAANDEL L . Trimethoprim：the overlooked component of trimethoprim-sulfamethoxazole idiosyncratic adverse drug reactions [J ] . Pharmacoepidemiol Drug Saf ， 2018 ， 27 （ 8 ）： 949 - 951 .

NAKAMURA H ， UETRECHT J ， CRIBB A E ， et al . In vitro formation，disposition and toxicity of N-acetoxy-sulfamethoxazole，a potential mediator of sulfamethoxazole toxicity [J ] . J Pharmacol Exp Ther ， 1995 ， 274 （ 3 ）： 1099 - 1104 .

《复方磺胺甲噁唑治疗药物监测临床应用专家共识》编写组 . 复方磺胺甲噁唑治疗药物监测临床应用专家共识 [J ] . 中国感染与化疗杂志， 2024 ， 24 （ 5 ）： 497 - 506 .

LEEGWATER E ， BAIDJOE L ， WILMS E B ， et al . Population pharmacokinetics of trimethoprim/sulfamethoxazole：dosage optimization for patients with renal insufficiency or receiving continuous renal replacement therapy [J ] . Clin Pharmacol Ther ， 2025 ， 117 （ 1 ）： 184 - 192 .

卢张阳，梁培，祁慧，等 . 重症患者复方磺胺甲噁唑血药峰浓度与不良反应的相关性研究 [J ] . 中国医院药学杂志， 2023 ， 43 （ 2 ）： 207 - 210 .

潘欢妍，祁慧，梁培，等 . 重症耶氏肺孢子菌肺炎患者复方磺胺甲噁唑血药浓度监测的临床研究 [J ] . 中南药学， 2023 ， 21 （ 6 ）： 1653 - 1658 .

NARANJO C A ， BUSTO U ， SELLERS E M ， et al . A method for estimating the probability of adverse drug reactions [J ] . Clin Pharmacol Ther ， 1981 ， 30 （ 2 ）： 239 - 245 .

KNAUS W A ， DRAPER E A ， WAGNER D P ， et al . APACHE Ⅱ：a severity of disease classification system [J ] . Crit Care Med ， 1985 ， 13 （ 10 ）： 818 - 829 .

KETT D H ， SHORR A F ， REBOLI A C ， et al . Anidula-fungin compared with fluconazole in severely ill patients with candidemia and other forms of invasive candidiasis：support for the 2009 IDSA treatment guidelines for candidiasis [J ] . Crit Care ， 2011 ， 15 （ 5 ）： R253 .

GIANNASI S E ， VENUTI M S ， MIDLEY A D ， et al . Mortality risk factors in elderly patients in intensive care without limitation of therapeutic effort [J ] . Med Intensiva（Engl Ed）， 2018 ， 42 （ 8 ）： 482 - 489 .

KASAPOĞLU U S ， KAÇMAZ O ， GÖK A ， et al . Prog-nostic factors for 30-days mortality in eighty years aged and older critically ill patients：a single center retrospective cohort study [J ] . Turk J Med Sci ， 2021 ， 51 （ 6 ）： 2968 - 2977 .

GRIEBLING T L . Re：trimethoprim use for urinary tract infection and risk of adverse outcomes in older patients：cohort study [J ] . J Urol ， 2019 ， 201 （ 1 ）： 9 - 10 .

SHIMIZU Y ， HIRAI T ， OGAWA Y ， et al . Characteristics of risk factors for acute kidney injury among inpatients administered sulfamethoxazole/trimethoprim：a retrospe-ctive observational study [J ] . J Pharm Health Care Sci ， 2022 ， 8 （ 1 ）： 20 .

KLINKER H ， LANGMANN P ， ZILLY M ， et al . Drug monitoring during the treatment of AIDS-associated Pneumocystis carinii pneumonia with trimethoprim-sulfa-methoxazole [J ] . J Clin Pharm Ther ， 1998 ， 23 （ 2 ）： 149 - 154 .

ALBALA D M ， PRIEN E L JR ， GALAL H A . Urolithiasis as a hazard of sulfonamide therapy [J ] . J Endourol ， 1994 ， 8 （ 6 ）： 401 - 403 .

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