Mancheño-Losa Mikel, Murillo Oscar, Benavent Eva, Sorlí Luisa, Riera Melchor, Cobo Javier, Benito Natividad, Morata Laura, Ribera Alba, Sobrino Beatriz, Fernández-Sampedro Marta, Múñez Elena, Bahamonde Alberto, Barbero José María, Del Toro Mª Dolores, Villa Jenifer, Rigo-Bonnin Raül, Luque Sonia, García-Luque Isabel, Oliver Antonio, Esteban Jaime, Lora-Tamayo Jaime
Department of Internal Medicine, Hospital Universitario 12 de Octubre, Instituto de Investigación Imas12, Madrid, Spain.
Grupo de Estudio de Infecciones Osteoarticulares - Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (GEIO-SEIMC), Madrid, Spain.
Infection. 2025 Feb;53(1):359-372. doi: 10.1007/s15010-024-02379-7. Epub 2024 Sep 9.
The prognosis of bone and joint infections (BJI) caused by Gram-negative bacilli (GNB) worsens significantly in the face of fluoroquinolone-resistance. In this setting, scarce pre-clinical and clinical reports suggest that intravenous beta-lactams plus colistin may improve outcome. Our aim was to assess the efficacy and safety of this treatment in a well-characterized prospective cohort.
Observational, prospective, non-comparative, multicenter (14 hospitals) study of adults with BJI caused by fluoroquinolone-resistant GNB treated with surgery and intravenous beta-lactams plus colistin for ≥ 21 days. The primary endpoint was the cure rate.
Of the 44 cases included (median age 72 years [IQR 50-81], 22 [50%] women), 32 (73%) had an orthopedic device-related infection, including 17 (39%) prosthetic joints. Enterobacterales were responsible for 27 (61%) episodes, and Pseudomonas spp for 17 (39%), with an overall rate of MDR/XDR GNB infections of 27/44 (61%). Patients were treated with colistin plus intravenous beta-lactam for 28 days (IQR 22-37), followed by intravenous beta-lactam alone for 19 days (IQR 5-35). The cure rate (intention-to-treat analysis; median follow-up = 24 months, IQR 19-30) was 82% (95% CI 68%-90%) and particularly, 80% (95% CI 55%-93%) among patients managed with implant retention. Adverse events (AEs) leading to antimicrobial withdrawal occurred in 10 (23%) cases, all of which were reversible. Colistin AEs were associated with higher plasma drug concentrations (2.8 mg/L vs. 0.9 mg/L, p = 0.0001).
Combination therapy with intravenous beta-lactams plus colistin is an effective regimen for BJI caused by fluoroquinolone-resistant GNB. AEs were reversible and potentially preventable by close therapeutic drug monitoring.
面对氟喹诺酮耐药情况，革兰氏阴性杆菌（GNB）引起的骨与关节感染（BJI）的预后显著恶化。在这种情况下，临床前和临床报告稀少，提示静脉用β-内酰胺类药物加黏菌素可能改善预后。我们的目的是在一个特征明确的前瞻性队列中评估这种治疗的疗效和安全性。
对因耐氟喹诺酮GNB引起BJI的成人患者进行观察性、前瞻性、非对照、多中心（14家医院）研究，采用手术及静脉用β-内酰胺类药物加黏菌素治疗≥21天。主要终点是治愈率。
纳入44例患者（中位年龄72岁[四分位间距50 - 81]，22例[50%]为女性），32例（73%）有骨科器械相关感染，其中17例（39%）为人工关节感染。肠杆菌科细菌导致27例（61%）感染事件，假单胞菌属导致17例（39%），耐多药/广泛耐药GNB感染总体发生率为27/44（61%）。患者接受黏菌素加静脉用β-内酰胺类药物治疗28天（四分位间距2 /span>2 - 37），随后仅接受静脉用β-内酰胺类药物治疗19天（四分位间距5 - 35）。治愈率（意向性分析；中位随访 = 24个月，四分位间距19 - 30）为82%（95%置信区间68% - 90%），特别是在保留植入物治疗的患者中为80%（95%置信区间55% - 93%）。导致抗菌药物停用的不良事件（AE）发生在10例（23%）患者中，所有这些事件均为可逆性。黏菌素AE与较高的血浆药物浓度相关（2.8 mg/L对0.9 mg/L，p = 0.0001）。
静脉用β-内酰胺类药物加黏菌素联合治疗是耐氟喹诺酮GNB引起的BJI的有效治疗方案。不良事件是可逆的，通过密切的治疗药物监测可能可预防。
