产碳青霉烯酶肠杆菌科所致骨髓炎实验兔模型中，达到骨杀菌效果对骨结构和骨髓的影响。

Effect of achieving bone sterilisation on bone architecture and bone marrow, in an experimental rabbit model of osteomyelitis caused by carbapenemase-producing Enterobacterales.

机构信息

UMR 1173, Versailles Saint-Quentin University, Versailles, France; Infectious Diseases Department, Raymond Poincaré Paris Saclay University Hospital, Garches, France.

UMR 1173, Versailles Saint-Quentin University, Versailles, France; FHU PROTHEE, St Louis-Lariboisière Hospital, Paris-Cité University, Paris, France.

出版信息

Int J Antimicrob Agents. 2023 Dec;62(6):107003. doi: 10.1016/j.ijantimicag.2023.107003. Epub 2023 Oct 14.

DOI:10.1016/j.ijantimicag.2023.107003

PMID:37839717

Abstract

OBJECTIVES

Natural history and treatment of bone infections caused by carbapenemase-producing Enterobacterales (CPE) are poorly defined. We evaluated the effect of treatment on the progression of subacute osteomyelitis in a rabbit model.

METHODS

Two isolates were used: a KPC-producing Klebsiella pneumoniae and an Escherichia coli harbouring bla and bla inserts, both susceptible to gentamicin, colistin, fosfomycin, and ceftazidime-avibactam. Osteomyelitis was induced in rabbits by tibial injection of 2 × 10 colony-forming units/mL. Antibiotics were started 14 d later, for 7 d, in 6 groups of 12 rabbits. Three days after treatment completion (D24), rabbits were euthanised and bones were cultured. Bone marrow and bone architecture macroscopic changes were evaluated through analysis of pictures by investigators unaware of the rabbit treatment group and microbiological outcome, using scales ranging from 0 (normal) to 3 (severe lesions) depending on modifications.

RESULTS

Bone marrow modifications induced by local infection were similar between prematurely deceased animals and non-sterilised animals (P = 0.14) but differed significantly from animals that achieved bone sterilisation after treatment (P = 0.04). Conversely, when comparing bone deformity, rabbits who died early (n = 13) had similar bone architecture as those achieving bone sterilisation (P = 0.12), as opposed to those not sterilised after treatment (P = 0.04). After a multivariate logistic regression, bone marrow scale ≤2 was associated with bone sterilisation (P < 0.001), and bone architecture scale ≤2 was associated with bone sterilisation (adjusted odds ratio = 2.7; 95% confidence interval 1.14-6.37) and KPC infection (adjusted odds ratio = 5.1; 95% confidence interval 2.17-12.13).

CONCLUSION

Effective antibacterial treatment reduces bone architecture distortion and bone marrow changes. These variables may be used as proxy for bone sterilisation.

摘要

目的

产碳青霉烯酶肠杆菌科（CPE）引起的骨感染的自然史和治疗方法尚未明确。我们评估了治疗方法对兔模型亚急性骨髓炎进展的影响。

方法

使用两种分离株：产 KPC 的肺炎克雷伯菌和携带 bla 和 bla 插入物的大肠埃希菌，两者均对庆大霉素、黏菌素、磷霉素和头孢他啶-阿维巴坦敏感。通过胫骨注射 2×10 个菌落形成单位/mL 诱导骨髓炎。在 14 天后，即第 14 天，对 12 只兔子的 6 个组开始使用抗生素治疗，共 7 天。治疗完成后 3 天（D24），处死兔子并对骨骼进行培养。通过对不知情的研究者拍摄的图片进行分析，评估骨髓和骨骼结构的宏观变化，使用从 0（正常）到 3（严重病变）的范围来评估病变程度，具体取决于病变的变化。

结果

局部感染引起的骨髓改变在提前死亡的动物和未消毒的动物之间相似（P=0.14），但与治疗后达到骨消毒的动物有显著差异（P=0.04）。相反，在比较骨骼畸形时，早期死亡的兔子（n=13）的骨骼结构与达到骨骼消毒的兔子相似（P=0.12），而与治疗后未消毒的兔子不同（P=0.04）。经过多变量逻辑回归，骨髓评分≤2 与骨骼消毒相关（P<0.001），骨骼结构评分≤2 与骨骼消毒相关（调整比值比=2.7；95%置信区间 1.14-6.37）和 KPC 感染相关（调整比值比=5.1；95%置信区间 2.17-12.13）。