Tomoyuki Yamada1, Satoshi Fujii2, Akari Shigemi3, Yoshio Takesue4. 1. Department of Pharmacy, Osaka Medical College Hospital, 2-7, Daigakumachi, Takatsuki, Osaka, 569-8686, Japan; Infection Control Center, Osaka Medical College Hospital, 2-7, Daigakumachi, Takatsuki, Osaka, 569-8686, Japan. Electronic address: phc032@osaka-med.ac.jp. 2. Department of Pharmacy, Sapporo Medical University Hospital, S1 W16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan. Electronic address: fujii.satoshi@sapmed.ac.jp. 3. Division of Medical and Environmental Safety, Department of Infection Control and Prevention, Kagoshima University Hospital, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan. Electronic address: a-shige@m3.kufm.kagoshima-u.ac.jp. 4. Department of Infection Prevention and Control, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan. Electronic address: takesuey@hyo-med.ac.jp.
Abstract
INTRODUCTION: Antimicrobial resistance is one of the biggest threats to public health systems worldwide, and aminoglycosides are key drugs for treating drug-resistant infections. Because of the nephrotoxicity of aminoglycosides, therapeutic drug monitoring is recommended, but few studies of the target trough concentration (Cmin) have been reported. To address the problem, we performed a meta-analysis to confirm the target Cmin of aminoglycosides for minimizing the risk of nephrotoxicity. METHODS: We conducted a literature search using MEDLINE, the Cochrane Library, and Ichushi-Web. In the meta-analysis, nephrotoxicity was compared between the Cmin ≥2 mg/L and Cmin <2 mg/L groups for gentamicin and between the Cmin ≥10 mg/L and Cmin <10 mg/L groups for amikacin. RESULTS: No randomized controlled trials were reported for any of the drugs. Five observational studies involving 615 patients were reported for gentamicin, and two observational studies involving 159 patients were identified for amikacin. For gentamicin, Cmin <2 mg/L was linked to a significantly lower rate of nephrotoxicity than Cmin ≥2 mg/L (odds ratio [OR] = 0.22, 95% confidence interval [CI] = 0.12-0.40). For amikacin, Cmin <10 mg/L was associated with a significantly lower rate of nephrotoxicity than Cmin ≥10 mg/L (OR = 0.05, 95% CI = 0.01-0.21). CONCLUSIONS: Although further well-controlled studies with a low risk of bias are needed, the current meta-analysis demonstrated that Cmin <2 mg/L and Cmin <10 mg/L may reduce the risk of nephrotoxicity linked to gentamicin and amikacin, respectively.
INTRODUCTION: Antimicrobial resistance is one of the biggest threats to public health systems worldwide, and aminoglycosides are key drugs for treating drug-resistant infections. Because of the nephrotoxicity of aminoglycosides, therapeutic drug monitoring is recommended, but few studies of the target trough concentration (Cmin) have been reported. To address the problem, we performed a meta-analysis to confirm the target Cmin of aminoglycosides for minimizing the risk of nephrotoxicity. METHODS: We conducted a literature search using MEDLINE, the Cochrane Library, and Ichushi-Web. In the meta-analysis, nephrotoxicity was compared between the Cmin ≥2 mg/L and Cmin <2 mg/L groups for gentamicin and between the Cmin ≥10 mg/L and Cmin <10 mg/L groups for amikacin. RESULTS: No randomized controlled trials were reported for any of the drugs. Five observational studies involving 615 patients were reported for gentamicin, and two observational studies involving 159 patients were identified for amikacin. For gentamicin, Cmin <2 mg/L was linked to a significantly lower rate of nephrotoxicity than Cmin ≥2 mg/L (odds ratio [OR] = 0.22, 95% confidence interval [CI] = 0.12-0.40). For amikacin, Cmin <10 mg/L was associated with a significantly lower rate of nephrotoxicity than Cmin ≥10 mg/L (OR = 0.05, 95% CI = 0.01-0.21). CONCLUSIONS: Although further well-controlled studies with a low risk of bias are needed, the current meta-analysis demonstrated that Cmin <2 mg/L and Cmin <10 mg/L may reduce the risk of nephrotoxicity linked to gentamicin and amikacin, respectively.
Authors: Hannah Yejin Kim; Kenneth C Byashalira; Scott K Heysell; Anne-Grete Märtson; Stellah G Mpagama; Prakruti Rao; Marieke G G Sturkenboom; Jan-Willem C Alffenaar Journal: Ther Drug Monit Date: 2022-02-01 Impact factor: 3.118
Authors: Caspar J Hodiamont; Annemieke K van den Broek; Suzanne L de Vroom; Jan M Prins; Ron A A Mathôt; Reinier M van Hest Journal: Clin Pharmacokinet Date: 2022-06-27 Impact factor: 5.577