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达托霉素用于儿童复杂性骨与关节感染:一项为期三年研究的真实世界疗效与安全性数据

Daptomycin for Pediatric Complex Bone and Joint Infections: Real-world Efficacy and Safety Data from a Three-year Study.

作者信息

Denina Marco, Abrate Giulia, Silvestro Erika, Funiciello Elisa, Pruccoli Giulia, Sandei Matteo, Mazzetti Giulia, Garazzino Silvia

机构信息

From the Department of Pediatrics, Infectious Diseases Unit, University of Turin, Regina Margherita Children's Hospital, Turin, Italy.

Department of Pediatrics and Public Health, University of Turin, Regina Margherita Children's Hospital, Turin, Italy.

出版信息

Pediatr Infect Dis J. 2025 Mar 14;44(8):e291-e295. doi: 10.1097/INF.0000000000004804.

Abstract

Bone and joint infections present a significant therapeutic challenge in children, particularly in complex or chronic cases. Staphylococcus aureus is the most common causative pathogen, with methicillin resistance rates varying by geographic location and hospital setting, underscoring the need for antibiotics effective against both methicillin-sensitive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus . Daptomycin, a cyclic lipopeptide antibiotic effective against gram-positive pathogens, is increasingly used off-label in pediatric osteomyelitis. This prospective study evaluates its real-world application, focusing on clinical outcomes, dosing strategies, safety, and therapeutic potential. Over a 3-year period, 20 children (median age: 13.5 years) with bone and joint infections were treated with daptomycin. The patient cohort was highly complex, with 70% having severe orthopedic or medical comorbidities. Methicillin-sensitive Staphylococcus aureus was isolated in 60% of cases, while MRSA was identified in 35%. Daptomycin was administered following bacteremia dosing guidelines, with some patients receiving higher doses (mean: 10 mg/kg). The median duration of daptomycin therapy was 24.5 days. Treatment was successful in 90% of cases, often transitioning to oral antibiotic therapy. C-reactive protein levels showed a median reduction of 90%. A composite score evaluating clinical response-including C-reactive protein levels, type of continuation therapy, and the need for surgery-indicated substantial improvement in the majority of patients, with a median score of 4. No severe adverse events were recorded, though transient neutropenia and elevated creatine kinase levels were observed in 2 cases. This study underscores daptomycin's safety and efficacy in treating complex pediatric osteoarticular infections and suggests its potential as a first-line therapy, particularly for MRSA cases. The comprehensive data reflect the current microbiological landscape of pediatric bone and joint infections, supporting the reconsideration of daptomycin's role in initial treatment protocols. Further research and controlled trials are warranted to confirm these findings and optimize treatment strategies.

摘要

骨与关节感染给儿童治疗带来了重大挑战,尤其是在复杂或慢性病例中。金黄色葡萄球菌是最常见的致病病原体,耐甲氧西林率因地理位置和医院环境而异,这突出表明需要对甲氧西林敏感金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌均有效的抗生素。达托霉素是一种对革兰氏阳性病原体有效的环脂肽抗生素,越来越多地在儿科骨髓炎中被超说明书使用。这项前瞻性研究评估了其在现实世界中的应用,重点关注临床结果、给药策略、安全性和治疗潜力。在3年期间,20名患有骨与关节感染的儿童(中位年龄:13.5岁)接受了达托霉素治疗。患者队列情况高度复杂,70%患有严重的骨科或内科合并症。60%的病例分离出甲氧西林敏感金黄色葡萄球菌,而35%的病例鉴定出耐甲氧西林金黄色葡萄球菌。达托霉素按照菌血症给药指南给药,一些患者接受了更高剂量(平均:10mg/kg)。达托霉素治疗的中位持续时间为24.5天。90%的病例治疗成功,通常过渡到口服抗生素治疗。C反应蛋白水平中位数降低了90%。一个评估临床反应的综合评分——包括C反应蛋白水平、继续治疗类型和手术需求——表明大多数患者有显著改善,中位评分为4分。未记录到严重不良事件,尽管2例患者出现了短暂性中性粒细胞减少和肌酸激酶水平升高。这项研究强调了达托霉素在治疗复杂儿童骨关节炎感染方面的安全性和有效性,并表明其作为一线治疗的潜力,特别是对于耐甲氧西林金黄色葡萄球菌病例。综合数据反映了儿童骨与关节感染当前的微生物学情况,支持重新考虑达托霉素在初始治疗方案中的作用。有必要进行进一步的研究和对照试验以证实这些发现并优化治疗策略。

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