De Gregori Simona, De Silvestri Annalisa, Capone Mara, Monzillo Vincenzina, Giordani Paola, Bruno Raffaele, Seminari Elena
Clinical and Experimental Pharmacokinetics Unit, Department of Diagnostic Medicine, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
SSD Biostatistica e Clinical Trial Center -Direzione Scientifica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Ther Adv Infect Dis. 2025 Jan 8;12:20499361241296232. doi: 10.1177/20499361241296232. eCollection 2025 Jan-Dec.
Daptomycin pharmacokinetics and pharmacodynamics data relative to higher doses in patients are necessary for clinical practice.
A monocentric, prospective study that enrolled patients with a diagnosis of spp. infective endocarditis treated with daptomycin according to clinical practice, to evaluate the pharmacokinetics/pharmacodynamics of different daptomycin daily doses (group A: 8-10 and group B: 11-12 mg/kg).
A monocentric, prospective, cohort study that enrolled patients with a diagnosis of spp. infective endocarditis treated with daptomycin. Daptomycin was administered by intravenous infusion over a 30-min period for at least five consecutive days before PK study.
Twenty-two patients were included. Native valve infectious endocarditis (IE) was diagnosed in 9 patients, prosthetic valve IE was diagnosed in 10 patients and 3 patients had concomitant intracardiac device infections. All patients showed a microbiologic response with negative blood cultures by day 5 (1-3 interquartile rate (IQR) 3-8). The median calculated AUC was 1298 (1-3 IQR 1069-1484) and 1459 (1-3 IQR 1218-1711) µg*h/mL, with the corresponding clearance of 0.49 (1-3 IQR 0.37-0.57) and 0.57 (1-3 IQR 0.40-0.71) L/h, respectively. A value of area under the curve/minimum inhibitory concentration (AUC/MIC) > 666 was reached by all patients; however, 4 out of 15 patients in group A and 1 out of 14 patients in group B did not reach the pharmacokinetic/pharmacodynamic (PK/PD) target of 1061; therefore, AUC/MIC equal to or above 1061 was reached by 73.3% in group A and 92.9% in group B.
From a PK/PD point of view, all patients reached the value of AUC/MIC > 666, while roughly 70% of patients in group A and 90% in group B reached the target value of AUC/MIC>1061. Even if this cut-off value is arbitrary, 11-12 mg/kg daily dose could be taken into consideration in case of serious infections characterised by a high inoculum or in cases of prosthetic valve infections.
临床实践需要与患者更高剂量相关的达托霉素药代动力学和药效学数据。
一项单中心前瞻性研究，纳入根据临床实践接受达托霉素治疗的确诊为 spp. 感染性心内膜炎的患者，以评估不同达托霉素每日剂量（A组：8 - 10mg/kg和B组：11 - 12mg/kg）的药代动力学/药效学。
一项单中心前瞻性队列研究，纳入确诊为 spp. 感染性心内膜炎并接受达托霉素治疗的患者。在进行药代动力学研究前，达托霉素通过静脉输注30分钟，连续至少五天给药。
纳入22例患者。9例诊断为天然瓣膜感染性心内膜炎（IE），10例诊断为人工瓣膜IE，3例伴有心内装置感染。所有患者在第5天血培养均呈阴性，显示出微生物学反应（四分位数间距（IQR）1 - 3为3 - 8）。计算得到的AUC中位数分别为1298（IQR 1 - 3为1069 - 1484）和1459（IQR 1 - 3为1218 - 1711）μg*h/mL，相应的清除率分别为0.49（IQR 1 - 3为0.37 - 0.57）和0.57（IQR 1 - 3为0.40 - 0.71）L/h。所有患者的曲线下面积/最低抑菌浓度（AUC/MIC）值均>666；然而，A组15例患者中有4例、B组14例患者中有1例未达到1061的药代动力学/药效学（PK/PD）目标；因此，A组73.3%、B组92.9%的患者达到了AUC/MIC等于或高于1061。
从PK/PD角度来看，所有患者的AUC/MIC值均>666，而A组约70%、B组约90%的患者达到了AUC/MIC>1061的目标值。即使这个临界值是任意设定的，但对于接种量大的严重感染或人工瓣膜感染病例，可考虑每日剂量为11 - 12mg/kg。
