Pai Manjunath P, Mercier Renee-Claude, Allen Sarah E
College of Pharmacy, University of New Mexico, Albuquerque, 87131, USA.
Ann Pharmacother. 2006 Mar;40(3):553-8. doi: 10.1345/aph.1G509. Epub 2006 Feb 28.
To report a case in which vancomycin clearance was used to determine the daptomycin dosing interval in a morbidly obese patient with renal impairment.
A 46-year-old man (209 kg; 178 cm) failed a 42 day course of vancomycin therapy for treatment of a methicillin-resistant Staphylococcus aureus-infected wound and cellulitis. The median trough vancomycin concentration was 12.6 microg/mL (range 7.3-24.1) through his course of therapy. Estimation of creatinine clearance (Cl(cr)) was confounded in this clinical scenario, given the patient's weight and a lack of valid equations in this patient population. Daptomycin was administered empirically at 6 mg/kg dosed every 48 hours based on estimated clearance from measured vancomycin concentrations. Steady-state plasma concentrations of daptomycin were determined, and the daptomycin half-life in this patient was more accurately estimated using vancomycin clearance as a surrogate. In addition, a 4 mg/kg dose of daptomycin would have been sufficient based on plasma concentrations. The patient demonstrated rapid clinical improvement and remained free of cellulitis for 6 months after completion of daptomycin and a 12 week course of trimethoprim/sulfamethoxazole.
The dosing interval of daptomycin is adjusted based on Cl(cr). However, estimation of Cl(cr) is difficult in morbidly obese patients with renal impairment, given a lack of valid equations. In this clinical scenario, vancomycin concentrations were used to estimate Cl(cr) and served as a surrogate measure to determine the daptomycin dosing interval. Measured daptomycin concentrations validated this approach and confirmed the inadequacy of commonly used Cl(cr) equations.
In this clinical scenario, vancomycin concentrations more accurately estimated Cl(cr), thereby facilitating determination of the daptomycin dosing interval.
报告1例通过万古霉素清除率来确定达托霉素给药间隔的病例，该患者为病态肥胖且伴有肾功能损害。
一名46岁男性（体重209 kg，身高178 cm）因耐甲氧西林金黄色葡萄球菌感染的伤口及蜂窝织炎接受了42天的万古霉素治疗，但治疗失败。在整个治疗过程中，万古霉素的中位谷浓度为12.6 μg/mL（范围7.3 - 24.1）。鉴于患者体重以及该患者群体缺乏有效的公式，在此临床情况下，肌酐清除率（Cl(cr)）的估算受到干扰。基于从测得的万古霉素浓度估算的清除率，经验性给予达托霉素，剂量为6 mg/kg，每48小时给药一次。测定了达托霉素的稳态血药浓度，并以万古霉素清除率作为替代指标更准确地估算了该患者的达托霉素半衰期。此外，根据血药浓度，4 mg/kg的达托霉素剂量本就足够。患者临床症状迅速改善，在完成达托霉素治疗及12周的甲氧苄啶/磺胺甲恶唑治疗后，6个月内未再出现蜂窝织炎。
达托霉素的给药间隔根据Cl(cr)进行调整。然而，对于病态肥胖且伴有肾功能损害的患者，由于缺乏有效的公式，Cl(cr)的估算较为困难。在此临床情况下，利用万古霉素浓度来估算Cl(cr)，并作为确定达托霉素给药间隔的替代指标。测得的达托霉素浓度验证了该方法，并证实了常用Cl(cr)公式的不足。
在此临床情况下，万古霉素浓度能更准确地估算Cl(cr)，从而有助于确定达托霉素的给药间隔。
