Krsak Martin, Morrisette Taylor, Damioli Laura, Flues Brandon, Liu Eugene W, Zhou Anna Y, Msdi Abdulwhab Shremo, McLeod Caleb, Akundi Saagar, Redell Mark, Molina Kyle C
Division of Infectious Diseases, Department of Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, USA.
Department of Clinical Pharmacy and Outcomes Sciences, Medical University of South Carolina College of Pharmacy, Charleston, SC, USA.
Clin Orthop Relat Res. 2025 Mar 14;483(7):1225-33. doi: 10.1097/CORR.0000000000003449.
Vancomycin-resistant enterococcus (VRE) infections pose substantial challenges for the treatment and suppression of bone and joint infections. Oritavancin, a long-acting lipoglycopeptide antibiotic, has shown promising in vitro activity against VRE. Limited data are available on using oritavancin for bone and joint infections caused by VRE, both for treatment (therapy to eliminate active infection) and suppressive antimicrobial therapy (long-term antibiotic administration to prevent infection recurrence in patients at high risk for that complication).
QUESTIONS/PURPOSES: (1) What proportion of patients in a small case series achieve freedom from infectious symptoms with use of oritavancin for treatment of VRE bone and joint infections? (2) What proportion of patients achieve freedom from infection recurrence with use of oritavancin when used for suppressive antimicrobial therapy of VRE bone and joint infections? (3) What proportion of patients develop adverse drug events associated with oritavancin use in VRE bone and joint infections?
We describe a retrospective, multicenter, observational case series of patients who received oritavancin for treatment and/or suppressive antimicrobial therapy of VRE bone and joint infection, including osteomyelitis, native septic arthritis, myositis, and prosthetic joint infection, between December 2014 and April 2024. The minimum surveillance period was 1 year, unless infection recurrence or an adverse drug event was documented before 1 year. Patients were excluded if they had a life expectancy of less than 7 days, dual use of VRE antibiotics, or brain or spinal cord abscesses related to VRE, although no patients met these exclusion criteria in our study group. Clinical signs and symptoms of infection, corresponding microbiological cultures, and adverse drug events were assessed throughout follow-up. Eleven patients (6 treatment, 5 suppressive antimicrobial therapy) with VRE (all Enterococcus faecium) bone and joint infection in which at least one dose of oritavancin was used were included. No patients were excluded because of insufficient follow-up time. In the treatment group, the median (range) age was 60 years (48 to 66), 4 of 6 patients were male, and patients had received prior therapy for VRE with either linezolid or daptomycin. Infections were hardware-associated osteomyelitis in 2 of 6 patients, osteomyelitis in 3 of 6, and prosthetic joint infection in 1 of 6. In the suppressive antimicrobial therapy group, the median (range) age was 61 years (25 to 68), and 3 of 5 patients were female. Four of 5 patients had hardware-associated infections, including 3 of 5 with hardware-associated osteomyelitis and 1 of 5 with prosthetic joint infection of the hip.
In the treatment group, 2 of 6 patients remained symptom free at a minimum follow-up of 3 years (range 3.0 to 3.25), and 2 patients developed recurrent infection-one with worsening knee stiffness and growth of VRE and one with radiologic signs of osteomyelitis and growth of methicillin-susceptible Staphylococcus aureus and Candida glabrata. One of 6 patients in the treatment group was lost to follow-up, and one pursued end-of-life care after 28 days. All 5 patients who underwent suppressive antimicrobial therapy remained free from recurrent symptoms with a minimum duration of therapy of 21 months (range 21 to 48). After 48 months of oritavancin as suppressive antimicrobial therapy, one patient in the cohort developed an infusion reaction-shortness of breath, cough, and hypotension-resulting in drug discontinuation.
In this small, retrospective cohort of patients with multiple comorbidities, oritavancin showed possible promise as suppressive antimicrobial therapy for VRE bone and joint infection, with all patients receiving suppressive antimicrobial therapy lacking recurrence of infectious symptoms. However, the role of oritavancin as treatment-in salvage situations after multiple therapies failed-appeared more limited in preventing infection recurrence. Larger studies are needed to further define the role of oritavancin in the treatment of VRE bone and joint infections.
Level IV, therapeutic study.
耐万古霉素肠球菌（VRE）感染给骨与关节感染的治疗和控制带来了巨大挑战。奥利万星是一种长效脂糖肽类抗生素，已显示出对VRE有良好的体外活性。关于使用奥利万星治疗VRE引起的骨与关节感染的数据有限，包括治疗（消除活动性感染的疗法）和抑制性抗菌治疗（长期使用抗生素以防止高风险患者感染复发）。
问题/目的：（1）在一个小病例系列中，使用奥利万星治疗VRE骨与关节感染的患者中，有多少比例的患者感染症状消失？（2）使用奥利万星对VRE骨与关节感染进行抑制性抗菌治疗时，有多少比例的患者感染未复发？（3）在VRE骨与关节感染中，使用奥利万星的患者发生药物不良事件的比例是多少？
我们描述了一个回顾性、多中心、观察性病例系列，这些患者在2014年12月至2024年4月期间接受奥利万星治疗和/或抑制性抗菌治疗VRE骨与关节感染，包括骨髓炎、原发性化脓性关节炎、肌炎和人工关节感染。最短随访期为1年，除非在1年前记录到感染复发或药物不良事件。如果患者预期寿命少于7天、同时使用VRE抗生素或与VRE相关的脑或脊髓脓肿，则排除这些患者，尽管我们的研究组中没有患者符合这些排除标准。在整个随访过程中评估感染的临床体征和症状、相应的微生物培养以及药物不良事件。纳入了11例使用过至少一剂奥利万星治疗VRE（均为粪肠球菌）骨与关节感染的患者（6例治疗，5例抑制性抗菌治疗）。没有患者因随访时间不足而被排除。治疗组中，年龄中位数（范围）为60岁（48至66岁），6例患者中有4例为男性，患者之前接受过利奈唑胺或达托霉素治疗VRE。6例患者中有2例感染与植入物相关的骨髓炎，3例为骨髓炎，1例为人工关节感染。在抑制性抗菌治疗组中，年龄中位数（范围）为61岁（25至68岁），5例患者中有3例为女性。5例患者中有4例有与植入物相关的感染，包括5例中有3例与植入物相关的骨髓炎，5例中有1例为髋关节人工关节感染。
治疗组中，6例患者中有2例在至少3年（范围3.0至3.25年）的随访中无症状，2例患者发生复发性感染，1例膝关节僵硬加重且VRE生长，另1例有骨髓炎的影像学表现且甲氧西林敏感金黄色葡萄球菌和光滑念珠菌生长。治疗组6例患者中有1例失访，1例在28天后接受临终关怀。接受抑制性抗菌治疗的所有5例患者在最短21个月（范围21至48个月）的治疗期间均未出现复发性症状。在使用奥利万星进行48个月的抑制性抗菌治疗后，队列中的1例患者出现输液反应——呼吸急促、咳嗽和低血压——导致停药。
在这个患有多种合并症的小回顾性队列中，奥利万星作为VRE骨与关节感染的抑制性抗菌治疗显示出可能的前景，所有接受抑制性抗菌治疗的患者均未出现感染症状复发。然而，奥利万星作为在多种治疗失败后的挽救性治疗的作用，在预防感染复发方面似乎更有限。需要更大规模的研究来进一步确定奥利万星在治疗VRE骨与关节感染中的作用。
IV级，治疗性研究。
